{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:50:49Z","timestamp":1790985049666,"version":"4.1.0"},"reference-count":244,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Testicular dysgenesis syndrome (TDS) is a complex disorder of the male reproductive system related to disfunction of the fetal testis. The clinical features of TDS may be evident at birth or infancy (cryptorchidism, hypospadias and\/or reduced anogenital distance) or occur later in adulthood (testis cancer, infertility). Genetic background seems to be important for genetic predisposition, with new genes being associated with components of the syndrome in last years. Interestingly, the incidence of clinical manifestations of TDS has been increasing in many countries in recent decades, suggesting that genetic predisposition alone cannot explain this trend. Consequently, the hypothesis of multifactorial etiopathogenesis is becoming increasingly accepted nowadays, with environmental factors probably acting during early developmental stages in genetically predisposed individuals. Methods: In this narrative review, we aim to critically evaluate genetic and non-genetic factors involved in the pathogenesis of TDs. Results: Important associations with intrauterine growth disorders and maternal diseases (overweight\/obesity and diabetes) as well as lifestyle factors (e.g., smoking and alcohol abuse) were found. In such context, endocrine disruptors probably play a major role. These substances are widely used in industry and can exert estrogenic and antiandrogenic effects, potentially interfering with the development of the fetal gonad. Conclusions: Considering their possible impact on male sexual health, more attention should be focused on maternal modifiable factors to confirm with prospective studies the mixed results of available evidence.<\/jats:p>","DOI":"10.3390\/genes17010040","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic, Epigenetic, and Non-Genetic Factors in Testicular Dysgenesis Syndrome: A Narrative Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4945-6437","authenticated-orcid":false,"given":"Alessandro","family":"Ciarloni","sequence":"first","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"delli Muti","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sacco","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0061-7349","authenticated-orcid":false,"given":"Nicola","family":"Ambo","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Di Giacomi","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Perrone","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinella","family":"Balercia","sequence":"additional","affiliation":[{"name":"CDL Biomedical Laboratory Techniques, DADP Degree Courses, Azienda Ospedaliero Universitaria delle Marche, Faculty of Medicine and Surgery, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-5699","authenticated-orcid":false,"given":"Gianmaria","family":"Salvio","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1286-1521","authenticated-orcid":false,"given":"Giancarlo","family":"Balercia","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1016\/j.jpedsurg.2010.07.030","article-title":"What Is New in Cryptorchidism and Hypospadias\u2014A Critical Review on the Testicular Dysgenesis Hypothesis","volume":"45","author":"Thorup","year":"2010","journal-title":"J. Pediatr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.lfs.2017.11.039","article-title":"Is Testicular Dysgenesis Syndrome a Genetic, Endocrine, or Environmental Disease, or an Unexplained Reproductive Disorder?","volume":"194","author":"Xing","year":"2018","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13152","DOI":"10.1111\/and.13152","article-title":"Associations between Hypospadias, Cryptorchidism and Anogenital Distance: Systematic Review and Meta-Analysis","volume":"50","author":"Hua","year":"2018","journal-title":"Andrologia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0140-6736(25)00455-6","article-title":"Testicular Cancer","volume":"406","author":"Chavarriaga","year":"2025","journal-title":"Lancet"},{"key":"ref_5","first-page":"374","article-title":"Abnormal Morphology of Germ Cells in Two Infertile Men","volume":"80A","year":"1972","journal-title":"Acta Pathol. Microbiol. Scand. Sect. A Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/00001648-199601000-00004","article-title":"Genital Anomalies and Risk for Testicular Cancer in Danish Men","volume":"7","author":"Prener","year":"1996","journal-title":"Epidemiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/jnci\/djp457","article-title":"Familial Coaggregation of Cryptorchidism, Hypospadias, and Testicular Germ Cell Cancer: A Nationwide Cohort Study","volume":"102","author":"Schnack","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/ijc.28207","article-title":"Congenital Malformations and Testicular Germ Cell Tumors: Congenital Malformations and TGCT","volume":"133","author":"Trabert","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1111\/j.1600-0463.2001.tb05770.x","article-title":"Testicular Dysgenesis Syndrome: An Increasingly Common Developmental Disorder with Environmental Aspects","volume":"109","author":"Skakkebaek","year":"2001","journal-title":"APMIS"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/adc.2006.098319","article-title":"Consensus Statement on Management of Intersex Disorders","volume":"91","author":"Hughes","year":"2005","journal-title":"Arch. Dis. Child."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"bqz015","DOI":"10.1210\/endocr\/bqz015","article-title":"High Molecular Diagnosis Rate in Undermasculinized Males with Differences in Sex Development Using a Stepwise Approach","volume":"161","author":"Jacobson","year":"2020","journal-title":"Endocrinology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000519964","article-title":"Environmental Impacts on Male Reproductive Development: Lessons from Experimental Models","volume":"96","author":"Jorgensen","year":"2023","journal-title":"Horm. Res. Paediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/aja.2012.126","article-title":"The Relationship between Anogenital Distance and the Androgen Receptor CAG Repeat Length","volume":"15","author":"Eisenberg","year":"2013","journal-title":"Asian J. Androl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1515\/bmc-2015-0006","article-title":"Involvement of Epigenetic Modifiers in the Pathogenesis of Testicular Dysgenesis and Germ Cell Cancer","volume":"6","author":"Lawaetz","year":"2015","journal-title":"Biomol. Concepts"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.taap.2005.01.058","article-title":"Testicular Dysgenesis Syndrome and the Development and Occurrence of Male Reproductive Disorders","volume":"207","author":"Virtanen","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Allali, S., Muller, J.-B., Brauner, R., Louren\u00e7o, D., Boudjenah, R., Karageorgou, V., Trivin, C., Lottmann, H., Lortat-Jacob, S., and Nihoul-F\u00e9k\u00e9t\u00e9, C. (2011). Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024117"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/molehr\/gaaa033","article-title":"New Insights into the Potential Mechanisms of Spermatogenic Failure in Patients with Idiopathic Azoospermia","volume":"26","author":"Cai","year":"2020","journal-title":"Mol. Human Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41585-023-00816-0","article-title":"Improved Phenotypic Classification of Male Infertility to Promote Discovery of Genetic Causes","volume":"21","author":"Wyrwoll","year":"2024","journal-title":"Nat. Rev. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/humupd\/7.3.282","article-title":"Trends in the Incidence of Cryptorchidism and Hypospadias, and Methodological Limitations of Registry-Based Data","volume":"7","author":"Toppari","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s43032-020-00411-3","article-title":"Testicular Stem Cell Dysfunction Due to Environmental Insults Could Be Responsible for Deteriorating Reproductive Health of Men","volume":"28","author":"Bhartiya","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Stewart, M.K., Mattiske, D.M., and Pask, A.J. (2020). Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218377"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-3-031-82990-1_6","article-title":"Effect of Endocrine Disruptors on Testicular Function","volume":"1469","author":"Cheng","year":"2025","journal-title":"Molecular Male Reproductive Medicine; Advances in Experimental Medicine and Biology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.toxlet.2012.03.020","article-title":"State-of-the-science of endocrine disrupting chemicals","volume":"211","author":"Bergman","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/08927022.2013.814131","article-title":"In Silico Evidences for the Binding of Phthalates onto Human Estrogen Receptor \u03b1, \u03b2 Subtypes and Human Estrogen-Related Receptor \u03b3","volume":"40","author":"Pradeep","year":"2014","journal-title":"Mol. Simul."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"135369","DOI":"10.1016\/j.scitotenv.2019.135369","article-title":"Global Review of Phthalates in Edible Oil: An Emerging and Nonnegligible Exposure Source to Human","volume":"704","author":"Luo","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ullah, S., Ahmad, S., Guo, X., Ullah, S., Ullah, S., Nabi, G., and Wanghe, K. (2023). A Review of the Endocrine Disrupting Effects of Micro and Nano Plastic and Their Associated Chemicals in Mammals. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1084236"},{"key":"ref_27","first-page":"184","article-title":"Impact of Endocrine Disruptors in Cosmetics on Reproductive Function in Males and Females","volume":"43","author":"Lasaneya","year":"2025","journal-title":"J. Environ. Sci. Health C"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nicolella, H.D., and De Assis, S. (2022). Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094671"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gonsioroski, A., Mourikes, V.E., and Flaws, J.A. (2020). Endocrine Disruptors in Water and Their Effects on the Reproductive System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061929"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/GCO.0000000000000868","article-title":"The Impact of Air Pollution and Endocrine Disruptors on Reproduction and Assisted Reproduction","volume":"35","author":"Seli","year":"2023","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, X., Wen, Z., Wang, Y., Mo, J., Zhong, Y., and Ge, R.-S. (2020). Bisphenols and Leydig Cell Development and Function. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00447"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.reprotox.2020.04.078","article-title":"Prenatal Exposure to Phthalates and Male Reproductive System Development: Results from a Canadian Pregnancy Cohort Study","volume":"95","author":"Romao","year":"2020","journal-title":"Reprod. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.alcohol.2008.12.002","article-title":"Maternal Smoking, Alcohol, and Coffee Use during Pregnancy and Son\u2019s Risk of Testicular Cancer","volume":"43","author":"Cohn","year":"2009","journal-title":"Alcohol"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yang, L., Wang, H., Yang, L., Zhao, M., Guo, Y., Bovet, P., and Xi, B. (2022). Maternal Cigarette Smoking before or during Pregnancy Increases the Risk of Birth Congenital Anomalies: A Population-Based Retrospective Cohort Study of 12 Million Mother-Infant Pairs. BMC Med., 20.","DOI":"10.1186\/s12916-021-02196-x"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/ppe.12373","article-title":"Maternal Overweight and Obesity and Genital Anomalies in Male Offspring: A Population-Based Swedish Cohort Study","volume":"31","author":"Arendt","year":"2017","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/humupd\/dmac035","article-title":"Temporal Trends in Sperm Count: A Systematic Review and Meta-Regression Analysis of Samples Collected Globally in the 20th and 21st Centuries","volume":"29","author":"Levine","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.euf.2020.02.006","article-title":"Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA","volume":"7","author":"Lokeshwar","year":"2021","journal-title":"Eur. Urol. Focus"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1007\/s40618-025-02671-9","article-title":"Temporal Trends in Serum Testosterone and Luteinizing Hormone Levels Indicate an Ongoing Resetting of Hypothalamic-Pituitary-Gonadal Function in Healthy Men: A Systematic Review","volume":"48","author":"Santi","year":"2025","journal-title":"J. Endocrinol. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tanaka, T., Kojo, K., Suetomi, T., Nagumo, Y., Midorikawa, H., Matsuda, T., Nakazono, A., Shimizu, T., Fujimoto, S., and Ikeda, A. (2025). Distinct Clusters of Testosterone Levels, Symptoms, and Serum Trace Elements in Young Men: A Cross-Sectional Analysis. Nutrients, 17.","DOI":"10.3390\/nu17050867"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3390\/jcm13071986","article-title":"Environmental Factors as the Main Hormonal Disruptors of Male Fertility","volume":"13","author":"Wdowiak","year":"2024","journal-title":"J. Clin. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1056\/NEJMra2300476","article-title":"Health Effects of Fossil Fuel\u2013Derived Endocrine Disruptors","volume":"390","author":"Woodruff","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mambrini, S.P., Menichetti, F., Ravella, S., Pellizzari, M., De Amicis, R., Foppiani, A., Battezzati, A., Bertoli, S., and Leone, A. (2023). Ultra-Processed Food Consumption and Incidence of Obesity and Cardiometabolic Risk Factors in Adults: A Systematic Review of Prospective Studies. Nutrients, 15.","DOI":"10.3390\/nu15112583"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Petre, G., Francini-Pesenti, F., De Toni, L., Di Nisio, A., Mingardi, A., Cosci, I., Passerin, N., Ferlin, A., and Garolla, A. (2025). Role of Mediterranean Diet and Ultra-Processed Foods on Sperm Parameters: Data from a Cross-Sectional Study. Nutrients, 17.","DOI":"10.3390\/nu17132066"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ceretti, E., Bonaccio, M., Iacoviello, L., Di Castelnuovo, A., Ruggiero, E., Donato, F., Lorenzetti, S., Zani, D., and Montano, L. (2024). Consumption of Ultra-Processed Foods and Semen Quality in Healthy Young Men Living in Italy. Nutrients, 16.","DOI":"10.3390\/nu16234129"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.juro.2014.05.005","article-title":"Evaluation and Treatment of Cryptorchidism: AUA Guideline","volume":"192","author":"Kolon","year":"2014","journal-title":"J. Urol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"518","DOI":"10.14310\/horm.2002.1708","article-title":"Leydig Cell Clustering and Reinke Crystal Distribution in Relation to Hormonal Function in Adult Patients with Testicular Dysgenesis Syndrome (TDS) Including Cryptorchidism","volume":"15","author":"Soerensen","year":"2016","journal-title":"Hormones"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.reprotox.2013.08.009","article-title":"Sertoli Cell Dedifferentiation in Human Cryptorchidism and Gender Reassignment Shows Similarities between Fetal Environmental and Adult Medical Treatment Estrogen and Antiandrogen Exposure","volume":"42","author":"Nistal","year":"2013","journal-title":"Reprod. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/humupd\/dmp011","article-title":"Biology of Insulin-like Factor 3 in Human Reproduction","volume":"15","author":"Ivell","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1007\/s00383-020-04745-6","article-title":"Correction to: The G178A Polymorphic Variant of INSL3 May Be Linked to Cryptorchidism among Egyptian Pediatric Cohort","volume":"36","author":"Tawfik","year":"2020","journal-title":"Pediatr. Surg. Int."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"F\u00e9nichel, P., Chevalier, N., Lahlou, N., Coquillard, P., Wagner-Mahler, K., Pugeat, M., Pana\u00efa-Ferrari, P., and Brucker-Davis, F. (2018). Endocrine Disrupting Chemicals Interfere with Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00786"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1749-6632.2008.03787.x","article-title":"New Roles for INSL3 in Adults","volume":"1160","author":"Ferlin","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.sjbs.2017.12.005","article-title":"Autosomal Single-Gene Disorders Involved in Human Infertility","volume":"25","author":"Jedidi","year":"2018","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.rbmo.2014.04.017","article-title":"A Novel Alu-Mediated Microdeletion at 11p13 Removes WT1 in a Patient with Cryptorchidism and Azoospermia","volume":"29","author":"Seabra","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5083569","DOI":"10.1155\/2016\/5083569","article-title":"Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study","volume":"2016","author":"Tirabassi","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e22567","DOI":"10.1096\/fj.202200558R","article-title":"Gene Dosage Changes in KCTD13 Result in Penile and Testicular Anomalies via Diminished Androgen Receptor Function","volume":"36","author":"Seth","year":"2022","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12610-023-00199-7","article-title":"Epigenetics, Cryptorchidism, and Infertility","volume":"33","author":"Hadziselimovic","year":"2023","journal-title":"Basic Clin. Androl."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"110453","DOI":"10.1016\/j.mce.2019.110453","article-title":"Identification and Functional Characterization of microRNAs in Rat Leydig Cells during Development from the Progenitor to the Adult Stage","volume":"493","author":"Chen","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"RP89284","DOI":"10.7554\/eLife.89284.3","article-title":"DMRT1 Is a Testis-Determining Gene in Rabbits and Is Also Essential for Female Fertility","volume":"12","author":"Dujardin","year":"2023","journal-title":"Elife"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"132.e1","DOI":"10.1016\/j.jpurol.2015.02.007","article-title":"The Variations in the AXIN1 Gene and Susceptibility to Cryptorchidism","volume":"11","author":"Zhou","year":"2015","journal-title":"J. Pediatr. Urol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000357931","article-title":"Decreased Expression of Genes Associated with Memory and X-Linked Mental Retardation in Boys with Non-Syndromic Cryptorchidism and High Infertility Risk","volume":"5","author":"Hadziselimovic","year":"2014","journal-title":"Mol. Syndromol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000442059","article-title":"Molecular Pathology of Cryptorchidism-Induced Infertility","volume":"9","author":"Docampo","year":"2015","journal-title":"Sex. Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"114241","DOI":"10.1016\/j.ecoenv.2022.114241","article-title":"Identification of Endocrine-Disrupting Chemicals Targeting the Genes and Pathways of Genital Anomalies in Males","volume":"247","author":"Zhou","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Holmboe, S.A., Beck, A.L., Andersson, A.-M., Main, K.M., J\u00f8rgensen, N., Skakkeb\u00e6k, N.E., and Priskorn, L. (2024). The Epidemiology of Cryptorchidism and Potential Risk Factors, Including Endocrine Disrupting Chemicals. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1343887"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00431-017-2864-5","article-title":"Hypospadias, All There Is to Know","volume":"176","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1136\/jmedgenet-2011-100174","article-title":"A Genome-Wide Association Study of Men with Symptoms of Testicular Dysgenesis Syndrome and Its Network Biology Interpretation","volume":"49","author":"Dalgaard","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jpurol.2025.01.002","article-title":"Comparing the Incidence of Hypospadias across the United States: A Contemporary Analysis","volume":"21","author":"Lavoie","year":"2025","journal-title":"J. Pediatr. Urol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"152.e1","DOI":"10.1016\/j.jpurol.2015.12.002","article-title":"Worldwide Prevalence of Hypospadias","volume":"12","author":"Springer","year":"2016","journal-title":"J. Pediatr. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41443-022-00563-7","article-title":"Hypospadias: Lessons Learned. An Overview of Incidence, Epidemiology, Surgery, Research, Complications, and Outcomes","volume":"35","author":"Wood","year":"2023","journal-title":"Int. J. Impot. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/bdr2.1415","article-title":"Maternal Hypertension and Hypospadias in Offspring: A Systematic Review and Meta-Analysis","volume":"111","author":"Sheriff","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_71","first-page":"e91204","article-title":"Experimentally Induced Testicular Dysgenesis Syndrome Originates in the Masculinization Programming Window","volume":"2","author":"Kilcoyne","year":"2017","journal-title":"JCI Insight"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1042\/BST20200200","article-title":"Androgens and the Masculinization Programming Window: Human-Rodent Differences","volume":"48","author":"Sharpe","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_73","first-page":"689","article-title":"Could Androgen Receptor Gene CAG Tract Polymorphism Affect Spermatogenesis in Men with Idiopathic Infertility?","volume":"31","author":"Giagulli","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.rbmo.2016.03.012","article-title":"Impact of CAG Repeat Length in the Androgen Receptor Gene on Male Infertility\u2014A Meta-Analysis","volume":"33","author":"Xiao","year":"2016","journal-title":"Reprod. Biomed. Online"},{"key":"ref_75","first-page":"157","article-title":"Androgen Receptor CAG and GGN Polymorphisms in Boys with Isolated Hypospadias","volume":"25","author":"Lardone","year":"2012","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.4238\/2015.March.6.5","article-title":"Androgen Receptor Gene CAG Repeat Polymorphism and Risk of Isolated Hypospadias: Results from a Meta-Analysis","volume":"14","author":"Huang","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Adamovic, T., and Nordenskj\u00f6ld, A. (2012). The CAG Repeat Polymorphism in the Androgen Receptor Gene Modifies the Risk for Hypospadias in Caucasians. BMC Med. Genet., 13.","DOI":"10.1186\/1471-2350-13-109"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2605.2009.01050.x","article-title":"Testicular Dysgenesis Syndrome Comprises Some but Not All Cases of Hypospadias and Impaired Spermatogenesis","volume":"33","author":"Main","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.3390\/cimb46050274","article-title":"Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features","volume":"46","author":"Luppino","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1530\/EJE-09-0067","article-title":"The Spectrum of Phenotypes Associated with Mutations in Steroidogenic Factor 1 (SF-1, NR5A1, Ad4BP) Includes Severe Penoscrotal Hypospadias in 46,XY Males without Adrenal Insufficiency","volume":"161","author":"Lin","year":"2009","journal-title":"Eur. J. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.1002\/jcp.27350","article-title":"The Genetic Factors Contributing to Hypospadias and Their Clinical Utility in Its Diagnosis","volume":"234","author":"Joodi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"E1131","DOI":"10.1210\/jc.2010-2804","article-title":"Analysis of the Wilms\u2019 Tumor Suppressor Gene (WT1) in Patients 46,XY Disorders of Sex Development","volume":"96","author":"Biebermann","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1159\/000441988","article-title":"The Genetic and Environmental Factors Underlying Hypospadias","volume":"9","author":"Bouty","year":"2015","journal-title":"Sex. Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/cge.13432","article-title":"Molecular Genetics of Hypospadias and Cryptorchidism Recent Developments","volume":"95","author":"Kalfa","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1152\/physrev.00017.2015","article-title":"Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility","volume":"96","author":"Skakkebaek","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"E1953","DOI":"10.1210\/jc.2011-0511","article-title":"Evidence for Epigenetic Abnormalities of the Androgen Receptor Gene in Foreskin from Children with Hypospadias","volume":"96","author":"Vottero","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12715","DOI":"10.1038\/s41598-020-69725-1","article-title":"Altered Mechanisms of Genital Development Identified through Integration of DNA Methylation and Genomic Measures in Hypospadias","volume":"10","author":"Richard","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2392048","DOI":"10.1080\/15592294.2024.2392048","article-title":"Genome-Wide Methylation Analysis in Patients with Proximal Hypospadias\u2014A Pilot Study and Review of the Literature","volume":"19","author":"Boers","year":"2024","journal-title":"Epigenetics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jpurol.2024.07.001","article-title":"The Possible Role of Epigenetics in the Etiology of Hypospadias","volume":"20","author":"Zhuri","year":"2024","journal-title":"J. Pediatr. Urol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1590\/s1677-5538.ibju.2019.0387","article-title":"Effects of Testicular Dysgenesis Syndrome Components on Testicular Germ Cell Tumor Prognosis and Oncological Outcomes","volume":"46","author":"Selvi","year":"2020","journal-title":"Int. Braz. J. Urol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11255-022-03359-2","article-title":"Effects of Epidemiological Risk Factors on Prognosis in Testicular Cancer","volume":"55","author":"Demirci","year":"2022","journal-title":"Int. Urol. Nephrol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/ijc.32810","article-title":"Testicular Cancer Incidence Predictions in Europe 2010\u20132035: A Rising Burden despite Population Ageing","volume":"147","author":"Znaor","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"33.e1","DOI":"10.1016\/j.urolonc.2012.12.002","article-title":"Changes in Epidemiologic Features of Testicular Germ Cell Cancer: Age at Diagnosis and Relative Frequency of Seminoma Are Constantly and Significantly Increasing","volume":"32","author":"Ruf","year":"2014","journal-title":"Urol. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1093\/jjco\/hyaa110","article-title":"Recent Malignant Testicular Tumor Trend in Japan, a Country with an Aging Population: A Large-Scale Study of 2012\u20132015 Hospital-Based Cancer Registry Data","volume":"50","author":"Kojo","year":"2020","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.mcna.2017.10.003","article-title":"Testicular Cancer","volume":"102","author":"Smith","year":"2018","journal-title":"Med. Clin. N. Am."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.eururo.2024.10.023","article-title":"Epidemiology and Risk Factors for Testicular Cancer: A Systematic Review","volume":"87","author":"Tateo","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.eururo.2022.06.016","article-title":"The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs\u2014Part A: Renal, Penile, and Testicular Tumours","volume":"82","author":"Moch","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S0140-6736(72)91909-5","article-title":"Possible Carcinoma-In-Situ of The Testis","volume":"300","year":"1972","journal-title":"Lancet"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/his.12958","article-title":"Germ Cell Neoplasia in Situ (GCNIS): Evolution of the Current Nomenclature for Testicular Pre-invasive Germ Cell Malignancy","volume":"69","author":"Berney","year":"2016","journal-title":"Histopathology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.semcdb.2015.09.013","article-title":"Pathogenesis of Germ Cell Neoplasia in Testicular Dysgenesis and Disorders of Sex Development","volume":"45","author":"Juul","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"794","DOI":"10.21037\/tau.2016.08.09","article-title":"Malignancy in Disorders of Sex Development","volume":"5","author":"Kathrins","year":"2016","journal-title":"Transl. Androl. Urol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/molehr\/gah059","article-title":"Identification of Genes Differentially Expressed in Testes Containing Carcinoma in Situ","volume":"10","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1158\/0008-5472.CAN-09-3301","article-title":"Malignant Germ Cell Tumors Display Common MicroRNA Profiles Resulting in Global Changes in Expression of Messenger RNA Targets","volume":"70","author":"Palmer","year":"2010","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2605.1987.tb00161.x","article-title":"Carcinoma-in-situ of the Testis: Possible Origin from Gonocytes and Precursor of All Types of Germ Cell Tumours except Spermatocytoma","volume":"10","author":"Berthelsen","year":"1987","journal-title":"Int. J. Androl."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1158\/0008-5472.CAN-04-0679","article-title":"Embryonic Stem Cell-Like Features of Testicular Carcinoma in Situ Revealed by Genome-Wide Gene Expression Profiling","volume":"64","author":"Almstrup","year":"2004","journal-title":"Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1158\/0008-5472.CAN-08-4554","article-title":"Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates That Testicular Carcinoma In Situ Is an Arrested Gonocyte","volume":"69","author":"Sonne","year":"2009","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/gcc.10244","article-title":"High-resolution Comparative Genomic Hybridization Detects Extra Chromosome Arm 12p Material in Most Cases of Carcinoma in Situ Adjacent to Overt Germ Cell Tumors, but Not before the Invasive Tumor Development","volume":"38","author":"Ottesen","year":"2003","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/path.1372","article-title":"Histological Evidence of Testicular Dysgenesis in Contralateral Biopsies from 218 Patients with Testicular Germ Cell Cancer","volume":"200","author":"Holm","year":"2003","journal-title":"J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1365-2559.1990.tb01115.x","article-title":"Malignant Sex Cord\u2013Stromal Tumour in a Patient with the Androgen Insensitivity Syndrome","volume":"16","author":"Gaffney","year":"1990","journal-title":"Histopathology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101800","DOI":"10.1016\/j.canep.2020.101800","article-title":"Risk of Gonadal Neoplasia in Patients with Disorders\/Differences of Sex Development","volume":"69","author":"Duranteau","year":"2020","journal-title":"Cancer Epidemiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s40618-022-01741-6","article-title":"Management of Male Factor Infertility: Position Statement from the Italian Society of Andrology and Sexual Medicine (SIAMS): Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR)","volume":"45","author":"Ferlin","year":"2022","journal-title":"J. Endocrinol. Invest."},{"key":"ref_112","first-page":"115","article-title":"The Genetics of Female and Male Infertility","volume":"122","author":"Wyrwoll","year":"2025","journal-title":"Dtsch. \u00c4rzteblatt Int."},{"key":"ref_113","first-page":"e14270","article-title":"Polymorphisms of Androgens-related Genes and Idiopathic Male Infertility in Turkish Men","volume":"54","author":"Hekim","year":"2022","journal-title":"Andrologia"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Osadchuk, L., Vasiliev, G., Kleshchev, M., and Osadchuk, A. (2022). Androgen Receptor Gene CAG Repeat Length Varies and Affects Semen Quality in an Ethnic-Specific Fashion in Young Men from Russia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810594"},{"key":"ref_115","first-page":"845","article-title":"CAG Repeat Polymorphism in Androgen Receptor and Infertility: A Case-Control Study","volume":"19","author":"Sharestani","year":"2021","journal-title":"Int. J. Reprod. BioMed."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000363609","article-title":"The Masculinization Programming Window","volume":"27","author":"Hiort","year":"2014","journal-title":"Endocrine Development"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1111\/andr.12863","article-title":"Short Anogenital Distance Is Associated with Testicular Germ Cell Tumour Development","volume":"8","author":"Casamonti","year":"2020","journal-title":"Andrology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/j.1365-2605.2012.01275.x","article-title":"The Relationship between Anogenital Distance and Azoospermia in Adult Men","volume":"35","author":"Eisenberg","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"174","DOI":"10.4103\/jhrs.jhrs_44_23","article-title":"Association between Late Manifestations of Testicular Dysgenesis Syndrome and Anogenital Distance: A Systematic Review and Meta-Analysis","volume":"16","author":"Tsutida","year":"2023","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/humrep\/deab162","article-title":"Testicular Cancer Survivors Have Shorter Anogenital Distance That Is Not Increased by 1 Year of Testosterone Replacement Therapy","volume":"36","author":"Priskorn","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e12500","DOI":"10.1002\/rmb2.12500","article-title":"The Ratio of 2nd to 4th Digit Length and Reproductive Function of Infertile Male Patients","volume":"22","author":"Uchida","year":"2023","journal-title":"Reprod. Med. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7846","DOI":"10.3168\/jds.2023-23427","article-title":"Genome-Wide Association Study of Anogenital Distance and Its (Co)Variances with Fertility in Growing and Lactating Holstein-Friesian Dairy Cattle","volume":"106","author":"Stephen","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"dev201710","DOI":"10.1242\/dev.201710","article-title":"Loss of NR5A1 in Mouse Sertoli Cells after Sex Determination Changes Cellular Identity and Induces Cell Death by Anoikis","volume":"150","author":"Condrea","year":"2023","journal-title":"Development"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/aja.2012.27","article-title":"A Pilot Study of the Association between Genetic Polymorphisms Involved in Estrogen Signaling and Infant Male Genital Phenotypes","volume":"14","author":"Sathyanarayana","year":"2012","journal-title":"Asian J. Androl."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Ciarloni, A., Delli Muti, N., Ambo, N., Perrone, M., Rossi, S., Sacco, S., Salvio, G., and Balercia, G. (2025). Contribution of Androgen Receptor CAG Repeat Polymorphism to Human Reproduction. DNA, 5.","DOI":"10.3390\/dna5010009"},{"key":"ref_126","first-page":"501","article-title":"Association Study of Novel Single Nucleotide Polymorphisms of Androgen Receptor and Estrogen Receptor-\u03b1 Genes with Male Infertility in Northwest of Iran: A Case-Control Study","volume":"20","author":"Ghadirkhomi","year":"2022","journal-title":"Int. J. Reprod. BioMed."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1093\/humrep\/deae195","article-title":"Biallelic RXFP2 Variants Lead to Congenital Bilateral Cryptorchidism and Male Infertility, Supporting a Role of RXFP2 in Spermatogenesis","volume":"39","author":"Syryn","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/and.12522","article-title":"Mutational Screening of the INSL3 Gene in Azoospermic Males with a History of Cryptorchidism","volume":"48","author":"Huang","year":"2016","journal-title":"Andrologia"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1093\/humrep\/dead105","article-title":"Bi-Allelic Variants in INSL3 and RXFP2 Cause Bilateral Cryptorchidism and Male Infertility","volume":"38","author":"Dicke","year":"2023","journal-title":"Hum. Reprod."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/humu.23916","article-title":"Mutation Update for the NR5A1 Gene Involved in DSD and Infertility","volume":"41","author":"Sousa","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.acuro.2023.08.002","article-title":"Correlaci\u00f3n entre el polimorfismo de los genes LHCGR y NR5A1y el riesgo de infertilidad masculina","volume":"48","author":"Behvarz","year":"2024","journal-title":"Actas Urol\u00f3gicas Espa\u00f1olas"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9640","DOI":"10.1002\/jcp.26876","article-title":"Deficiency of Fibroblast Growth Factor 2 (FGF-2) Leads to Abnormal Spermatogenesis and Altered Sperm Physiology","volume":"233","author":"Saucedo","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12610-022-00160-0","article-title":"A Novel Role for CFTR Interaction with LH and FGF in Azoospermia and Epididymal Maldevelopment Caused by Cryptorchidism","volume":"32","author":"Hadziselimovic","year":"2022","journal-title":"Basic Clin. Androl."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/molehr\/gax034","article-title":"Infertility Diagnosis Has a Significant Impact on the Transcriptome of Developing Blastocysts","volume":"23","author":"McCallie","year":"2017","journal-title":"MHR Basic Sci. Reprod. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s10815-021-02140-1","article-title":"Mutations in the Desert Hedgehog (DHH) Gene in the Disorders of Sexual Differentiation and Male Infertility","volume":"38","author":"Mehta","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"505","DOI":"10.24272\/j.issn.2095-8137.2022.440","article-title":"Transcription Factor Dmrt1 Triggers the SPRY1-NF-\u03baB Pathway to Maintain Testicular Immune Homeostasis and Male Fertility","volume":"44","author":"Zhang","year":"2023","journal-title":"Zool. Res."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhuang, X., Zeng, J., and Tzeng, C.-M. (2017). Integrated Analysis of DNA Methylation and mRNA Expression Profiles to Identify Key Genes in Severe Oligozoospermia. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00261"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/aja.aja_33_20","article-title":"Mutational Analysis of the GATA4 Gene in Chinese Men with Nonobstructive Azoospermia","volume":"23","author":"Zhang","year":"2021","journal-title":"Asian J. Androl."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1530\/REP-17-0302","article-title":"EZH2 Deletion Promotes Spermatogonial Differentiation and Apoptosis","volume":"154","author":"Jin","year":"2017","journal-title":"Reproduction"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/mrd.22430","article-title":"The SCF\/c-KIT System in the Male: Survival Strategies in Fertility and Cancer: SCF\/c-KIT System in Male Fertility and Cancer","volume":"81","author":"Cardoso","year":"2014","journal-title":"Mol. Reprod. Dev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s11427-023-2390-5","article-title":"The PIWI-Specific Insertion Module Helps Load Longer piRNAs for Translational Activation Essential for Male Fertility","volume":"66","author":"Wang","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.biocel.2016.08.005","article-title":"SOX9 Regulates Expression of the Male Fertility Gene Ets Variant Factor 5 (ETV5) during Mammalian Sex Development","volume":"79","author":"Alankarage","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Roshan, M.M., Azizi, H., Majelan, M.A., and Tabar, A.N. (2024). Sox9 Downregulation in Non-Obstructive Azoospermia by UTF1 and Mediator Role of POU5F1. BMC Res. Notes, 17.","DOI":"10.1186\/s13104-024-06711-0"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00441-017-2698-5","article-title":"Defective Wnt3 Expression by Testicular Sertoli Cells Compromise Male Fertility","volume":"371","author":"Basu","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/mrd.22768","article-title":"A Novel Functional Variant in Wilms\u2019 Tumor 1 (WT1) Is Associated with Idiopathic Non-obstructive Azoospermia","volume":"84","author":"Xu","year":"2017","journal-title":"Mol. Reprod. Dev."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"394","DOI":"10.5653\/cerm.2024.07584","article-title":"WT1 Pathogenic Variant in Azoospermic Infertile Men with an Isolated Undescended Testis","volume":"52","author":"Sharifi","year":"2025","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.jpurol.2012.10.024","article-title":"Cryptorchidism in Egyptian Neonates","volume":"9","author":"Zakaria","year":"2013","journal-title":"J. Pediatr. Urol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/cga.12061","article-title":"Possible Association of Maternal Factors with the Higher Risk of Isolated True Undescended Testis: A Population-based Case-control Study","volume":"54","author":"Mavrogenis","year":"2014","journal-title":"Congenit. Anom."},{"key":"ref_149","first-page":"904","article-title":"Testicular Cancer and Cryptorchidism in Relation to Prenatal Factors: Case-Control Studies in Denmark","volume":"8","year":"1997","journal-title":"Cancer Causes Control"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2605.2004.00473.x","article-title":"Risk Factors for Hypospadias in Norwegian Boys\u2014Association with Testicular Dysgenesis Syndrome?","volume":"27","author":"Aschim","year":"2004","journal-title":"Int. J. Androl."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, L., Yang, Z., Chen, F., Liu, Z., and Tang, Z. (2022). Association between Perinatal Factors and Hypospadias in Newborns: A Retrospective Case\u2013Control Study of 42,244 Male Infants. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-04906-6"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/bjc.1998.196","article-title":"Testicular Cancer Risk and Maternal Parity: A Population-Based Cohort Study","volume":"77","author":"Westergaard","year":"1998","journal-title":"Br. J. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1136\/jech.43.4.324","article-title":"Cryptorchidism: A Registry Based Study in Sweden on Some Factors of Possible Aetiological Importance","volume":"43","author":"Hjertkvist","year":"1989","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/ije\/dyp287","article-title":"A Systematic Review and Meta-Analysis of Perinatal Variables in Relation to the Risk of Testicular Cancer\u2014Experiences of the Mother","volume":"38","author":"Cook","year":"2009","journal-title":"Int. J. Epidemiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.ajog.2022.03.052","article-title":"Long-Term Health Outcomes of Children Born to Mothers with Hyperemesis Gravidarum: A Systematic Review and Meta-Analysis","volume":"227","author":"Nijsten","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2605.2007.00770.x","article-title":"The Frequency of Undescended Testis from Birth to Adulthood: A Review","volume":"31","author":"Sijstermans","year":"2008","journal-title":"Int. J. Androl."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Zhang, T.-N., Huang, X.-M., Zhao, X.-Y., Wang, W., Wen, R., and Gao, S.-Y. (2022). Risks of Specific Congenital Anomalies in Offspring of Women with Diabetes: A Systematic Review and Meta-Analysis of Population-Based Studies Including over 80 Million Births. PLoS Med., 19.","DOI":"10.1371\/journal.pmed.1003900"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/EDE.0000000000000781","article-title":"Maternal Diabetes Mellitus and Genital Anomalies in Male Offspring: A Nationwide Cohort Study in 2 Nordic Countries","volume":"29","author":"Arendt","year":"2018","journal-title":"Epidemiology"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1210\/jc.2006-1420","article-title":"Mild Gestational Diabetes as a Risk Factor for Congenital Cryptorchidism","volume":"91","author":"Virtanen","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.2337\/dc20-0261","article-title":"Association of Maternal Prepregnancy Diabetes and Gestational Diabetes Mellitus with Congenital Anomalies of the Newborn","volume":"43","author":"Wu","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wang, X.-H., Zheng, X.-M., Liu, T.-Z., Zhang, W.-B., Zheng, H., and Chen, M.-F. (2015). Maternal Gestational Smoking, Diabetes, Alcohol Drinking, Pre-Pregnancy Obesity and the Risk of Cryptorchidism: A Systematic Review and Meta-Analysis of Observational Studies. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119006"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/bdra.20805","article-title":"No Association between Maternal Pre-Pregnancy Obesity and Risk of Hypospadias or Cryptorchidism in Male Newborns","volume":"91","author":"Adams","year":"2011","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1001\/archpedi.161.8.745","article-title":"Prepregnancy Obesity as a Risk Factor for Structural Birth Defects","volume":"161","author":"Waller","year":"2007","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"488","DOI":"10.4103\/jiaps.jiaps_31_24","article-title":"Nongenetic Risk Factors of Severe Hypospadias: A Case\u2013Control Study","volume":"29","author":"Indriasari","year":"2024","journal-title":"J. Indian Assoc. Pediatr. Surg."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/bdra.20679","article-title":"Prepregnancy Obesity: A Complex Risk Factor for Selected Birth Defects","volume":"88","author":"Carmichael","year":"2010","journal-title":"Birth Defects Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s12978-022-01458-y","article-title":"Association of Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Neonatal Anogenital Distance in a Chinese Birth Cohort","volume":"19","author":"Wang","year":"2022","journal-title":"Reprod. Health"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1046\/j.1464-410x.2000.00436.x","article-title":"The Alspac Study Team a Maternal Vegetarian Diet in Pregnancy is Associated with Hypospadias","volume":"85","author":"North","year":"2000","journal-title":"BJU Int."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1365-3016.2012.01272.x","article-title":"Nutritional Factors and Hypospadias Risks","volume":"26","author":"Carmichael","year":"2012","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41390-023-02768-y","article-title":"Maternal Physical Activity, Sitting, and Risk of Non-Cardiac Birth Defects","volume":"95","author":"Evenson","year":"2024","journal-title":"Pediatr. Res."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Ye, Z.-H., Chen, H.-S., Zhang, Z.-C., Wang, X., Liu, X., and Wei, G.-H. (2023). Parental Smoking and Risk of Hypospadias: An Updated Meta-Analysis of Observational Studies. Front. Pediatr., 11.","DOI":"10.3389\/fped.2023.1003037"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/humupd\/dmr022","article-title":"Maternal Smoking in Pregnancy and Birth Defects: A Systematic Review Based on 173 687 Malformed Cases and 11.7 Million Controls","volume":"17","author":"Hackshaw","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00431-018-3303-y","article-title":"Correction to: Maternal Smoking during Pregnancy and Risk of Cryptorchidism: A Systematic Review and Meta-Analysis","volume":"178","author":"Yu","year":"2019","journal-title":"Eur. J. Pediatr."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/01.ede.0000254061.90686.9f","article-title":"Cryptorchidism According to Maternal Gestational Smoking","volume":"18","author":"Jensen","year":"2007","journal-title":"Epidemiology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"901","DOI":"10.2147\/CLEP.S368826","article-title":"Maternal Cigarette Smoking During Pregnancy and Genital Anomalies in Boys: A Register-Based Cohort and Sibling-Matched Design Study","volume":"14","author":"Lindbo","year":"2022","journal-title":"Clin. Epidemiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1365-3016.2005.00680.x","article-title":"Hypospadias and Maternal Exposures to Cigarette Smoke","volume":"19","author":"Carmichael","year":"2005","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1289\/ehp.10791","article-title":"Maternal and Gestational Risk Factors for Hypospadias","volume":"116","author":"Akre","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2147\/CLEP.S150657","article-title":"Lifestyle in Pregnancy and Cryptorchidism in Sons: A Study within Two Large Danish Birth Cohorts","volume":"10","author":"Kjersgaard","year":"2018","journal-title":"Clin. Epidemiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.ejca.2009.01.017","article-title":"Maternal Smoking during Pregnancy and Testicular Cancer in the Sons: A Nested Case-Control Study and a Meta-Analysis","volume":"45","author":"Tuomisto","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jpurol.2020.11.005","article-title":"Assisted Reproductive Technologies and the Risk of Congenital Urogenital Tract Malformations: A Systematic Review and Meta-Analysis","volume":"17","author":"Zhang","year":"2021","journal-title":"J. Pediatr. Urol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.urology.2012.12.003","article-title":"Does Infertility Treatment Increase Male Reproductive Tract Disorder?","volume":"81","author":"Bang","year":"2013","journal-title":"Urology"},{"key":"ref_181","first-page":"223","article-title":"Maternal Use of Mild Analgesics during Pregnancy Associated with Reduced Anogenital Distance in Sons: A Cohort Study of 1027 Mother-Child Pairs","volume":"32","author":"Lind","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Navarro-Lafuente, F., Arense-Gonzalo, J., Adoamnei, E., Prieto-S\u00e1nchez, M., S\u00e1nchez-Ferrer, M., Garc\u00eda-Marcos, L., Morales, E., Mendiola, J., Torres-Cantero, A., and The NELA Study Group (2021). Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18126338"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Hoeltzenbein, M., Stieler, K., Panse, M., Wacker, E., and Schaefer, C. (2013). Allopurinol Use during Pregnancy\u2014Outcome of 31 Prospectively Ascertained Cases and a Phenotype Possibly Indicative for Teratogenicity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066637"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1002\/ajmg.a.34139","article-title":"Potential Teratogenic Effects of Allopurinol: A Case Report","volume":"155","author":"Kozenko","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Veroniki, A.A., Cogo, E., Rios, P., Straus, S.E., Finkelstein, Y., Kealey, R., Reynen, E., Soobiah, C., Thavorn, K., and Hutton, B. (2017). Comparative Safety of Anti-Epileptic Drugs during Pregnancy: A Systematic Review and Network Meta-Analysis of Congenital Malformations and Prenatal Outcomes. BMC Med., 15.","DOI":"10.1186\/s12916-017-0845-1"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/bcp.14561","article-title":"Risk of Congenital Malformations in Offspring of Women Using \u0392-blockers during Early Pregnancy: An Updated Meta-analysis of Observational Studies","volume":"87","author":"Wu","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1161\/HYPERTENSIONAHA.111.00833","article-title":"The Risk of Congenital Malformations Associated with Exposure to \u03b2-Blockers Early in Pregnancy: A Meta-Analysis","volume":"62","author":"Yakoob","year":"2013","journal-title":"Hypertension"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.reprotox.2022.12.003","article-title":"Pregnancy Outcomes Following Maternal Macrolide Use: A Systematic Review and Meta-Analysis","volume":"115","author":"Erol","year":"2023","journal-title":"Reprod. Toxicol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/(SICI)1097-0215(19960503)66:3<287::AID-IJC2>3.0.CO;2-V","article-title":"Risks of Testicular Cancer and Cryptorchidism in Relation to Socio-Economic Status and Related Factors: Case-Control Studies in Denmark","volume":"66","author":"Moller","year":"1996","journal-title":"Int. J. Cancer"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1111\/andr.12422","article-title":"Paternal Age and Risk of Testicular Germ Cell Tumors: A Cohort Study of 1,000,000 Men","volume":"5","author":"Levine","year":"2017","journal-title":"Andrology"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Moustakli, E., Zikopoulos, A., Georgiou, I., Dimitriadis, F., Symeonidis, E.N., Markou, E., Michaelidis, T.M., Tien, D.M.B., and Giannakis, I. (2023). Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring. Genes, 14.","DOI":"10.3390\/genes14020486"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"520.e1","DOI":"10.1016\/j.jpurol.2019.07.001","article-title":"Occupational Exposure to Endocrine-Disrupting Chemicals and Other Parental Risk Factors in Hypospadias and Cryptorchidism Development: A Case\u2013Control Study","volume":"15","year":"2019","journal-title":"J. Pediatr. Urol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1111\/andr.13404","article-title":"Congenital Male Genital Malformations and Paternal Health: An Analysis of the US Claims Data","volume":"11","author":"Yu","year":"2023","journal-title":"Andrology"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/0140-6736(93)90953-E","article-title":"Are Oestrogens Involved in Falling Sperm Counts and Disorders of the Male Reproductive Tract?","volume":"341","author":"Sharpe","year":"1993","journal-title":"Lancet"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1177\/23727322231196794","article-title":"Endocrine-Disrupting Chemicals: Science and Policy","volume":"10","author":"Hilz","year":"2023","journal-title":"Policy Insights Behav. Brain Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/jb\/mvm158","article-title":"Structural Evidence for Endocrine Disruptor Bisphenol A Binding to Human Nuclear Receptor ERR","volume":"142","author":"Matsushima","year":"2007","journal-title":"J. Biochem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1289\/ehp.0800367","article-title":"Low Doses of Bisphenol a Promote Human Seminoma Cell Proliferation by Activating PKA and PKG via a Membrane G-Protein\u2013Coupled Estrogen Receptor","volume":"117","author":"Bouskine","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"49005","DOI":"10.18632\/oncotarget.16923","article-title":"Low Concentration of BPA Induces Mice Spermatocytes Apoptosis via GPR30","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Rehan, M., Ahmad, E., Sheikh, I.A., Abuzenadah, A.M., Damanhouri, G.A., Bajouh, O.S., AlBasri, S.F., Assiri, M.M., and Beg, M.A. (2015). Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-Bis-(P-Hydroxyphenyl)Pent-1-Ene\u2014A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138438"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.bbi.2011.02.005","article-title":"Epigenetic Perspective on the Developmental Effects of Bisphenol A","volume":"25","author":"Kundakovic","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/etc.1986","article-title":"Distinct Mechanisms of Endocrine Disruption of DDT-Related Pesticides toward Estrogen Receptor \u03b1 and Estrogen-Related Receptor \u03b3","volume":"31","author":"Zhuang","year":"2012","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1001-0742(08)60054-6","article-title":"Effects of p,P\u2032 -DDE Exposure on Gonadal Development and Gene Expression in Japanese Medaka (Oryzias latipes)","volume":"20","author":"Zhang","year":"2008","journal-title":"J. Environ. Sci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.scitotenv.2012.08.072","article-title":"Molecular Docking, Molecular Dynamics Simulation, and Structure-Based 3D-QSAR Studies on Estrogenic Activity of Hydroxylated Polychlorinated Biphenyls","volume":"441","author":"Li","year":"2012","journal-title":"Sci. Total Environ."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12940-018-0362-5","article-title":"Transgenerational Effects of Polychlorinated Biphenyls: 1. Development and Physiology across 3 Generations of Rats","volume":"17","author":"Mennigen","year":"2018","journal-title":"Environ. Health"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s44274-025-00257-z","article-title":"Preventive Antioxidant Strategies to Reduce the Effects of Phthalate Exposure on Reproductive Health","volume":"3","author":"Oyovwi","year":"2025","journal-title":"Discov. Environ."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxlet.2017.05.028","article-title":"Agonistic and Antagonistic Effects of Phthalates and Their Urinary Metabolites on the Steroid Hormone Receptors ER\u03b1, ER\u03b2, and AR","volume":"277","author":"Engel","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e907","DOI":"10.1038\/cddis.2013.420","article-title":"Androgen Receptor-Mediated Apoptosis in Bovine Testicular Induced Pluripotent Stem Cells in Response to Phthalate Esters","volume":"4","author":"Wang","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Amir, S., Shah, S.T.A., Mamoulakis, C., Docea, A.O., Kalantzi, O.-I., Zachariou, A., Calina, D., Carvalho, F., Sofikitis, N., and Makrigiannakis, A. (2021). Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18041464"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jsbmb.2011.08.007","article-title":"Endocrine Disrupting Chemicals and Disease Susceptibility","volume":"127","author":"Schug","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"119745","DOI":"10.1016\/j.envpol.2022.119745","article-title":"Associations of Maternal Urinary Bisphenol and Phthalate Concentrations with Offspring Reproductive Development","volume":"309","author":"Blaauwendraad","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/humupd\/dmz004","article-title":"Effect of Environmental and Pharmaceutical Exposures on Fetal Testis Development and Function: A Systematic Review of Human Experimental Data","volume":"25","author":"Kilcoyne","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.reprotox.2015.11.002","article-title":"Bisphenol A and Other Phenols in Human Placenta from Children with Cryptorchidism or Hypospadias","volume":"59","author":"Arrebola","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3390\/jox14010010","article-title":"Early Female Transgender Identity after Prenatal Exposure to Diethylstilbestrol: Report from a French National Diethylstilbestrol (DES) Cohort","volume":"14","author":"Gaspari","year":"2024","journal-title":"J. Xenobiotics"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Ristori, J., Cocchetti, C., Romani, A., Mazzoli, F., Vignozzi, L., Maggi, M., and Fisher, A.D. (2020). Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062123"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/S0140-6736(02)08152-7","article-title":"Hypospadias in Sons of Women Exposed to Diethylstilbestrol in Utero: A Cohort Study","volume":"359","author":"Klip","year":"2002","journal-title":"Lancet"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/bdra.20657","article-title":"Maternal Exposures to Endocrine Disrupting Chemicals and Hypospadias in Offspring","volume":"88","author":"Giordano","year":"2010","journal-title":"Birth Defects Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/ajmg.a.35815","article-title":"Case\u2013C Ontrol Study of Maternal Residential Atrazine Exposure and Male Genital Malformations","volume":"161","author":"Agopian","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"The National Birth Defects Prevention Study, Winston, J.J., Emch, M., Meyer, R.E., Langlois, P., Weyer, P., Mosley, B., Olshan, A.F., Band, L.E., and Luben, T.J. (2016). Hypospadias and Maternal Exposure to Atrazine via Drinking Water in the National Birth Defects Prevention Study. Environ. Health, 15, 76.","DOI":"10.1186\/s12940-016-0161-9"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1136\/oem.2009.047373","article-title":"Use of Biocides and Insect Repellents and Risk of Hypospadias","volume":"67","author":"Dugas","year":"2010","journal-title":"Occup. Environ. Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1289\/ehp.0800389","article-title":"Maternal Pregnancy Levels of Polychlorinated Biphenyls and Risk of Hypospadias and Cryptorchidism in Male Offspring","volume":"117","author":"McGlynn","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Rignell-Hydbom, A., Lindh, C.H., Dillner, J., J\u00f6nsson, B.A.G., and Rylander, L. (2012). A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044767"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1080\/10934529.2012.680387","article-title":"The Association between Some Endocrine Disruptors and Hypospadias in Biological Samples","volume":"47","author":"Choi","year":"2012","journal-title":"J. Environ. Sci. Health A"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/EDE.0b013e318246073e","article-title":"Maternal Urinary Phthalates and Phenols and Male Genital Anomalies","volume":"23","author":"Chevrier","year":"2012","journal-title":"Epidemiology"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/EDE.0000000000000198","article-title":"Amniotic Fluid Phthalate Levels and Male Fetal Gonad Function","volume":"26","author":"Jensen","year":"2015","journal-title":"Epidemiology"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s40572-018-0214-z","article-title":"Pharmacologic and Environmental Endocrine Disruptors in the Pathogenesis of Hypospadias: A Review","volume":"5","author":"Raghavan","year":"2018","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.eururo.2019.07.002","article-title":"International Trends in the Incidence of Testicular Cancer: Lessons from 35 Years and 41 Countries","volume":"76","author":"Gurney","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Elad, D., Jaffa, A.J., Grisaru, D., and Leibovitch, I. (2021). In Utero Programming of Testicular Cancer. J. Dev. Biol., 9.","DOI":"10.3390\/jdb9030035"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1210\/en.2019-00486","article-title":"Is Testicular Germ Cell Cancer Estrogen Dependent? The Role of Endocrine Disrupting Chemicals","volume":"160","author":"Chevalier","year":"2019","journal-title":"Endocrinology"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12020-022-03171-z","article-title":"Environmental Disruptors and Testicular Cancer","volume":"78","author":"Faja","year":"2022","journal-title":"Endocrine"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/jnci\/djn101","article-title":"Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors","volume":"100","author":"McGlynn","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"179054","DOI":"10.1016\/j.scitotenv.2025.179054","article-title":"Prenatal Exposure to Organochlorine Pesticides and Polychlorinated Biphenyls and Risk of Testicular Germ Cell Cancer Later in Life","volume":"970","author":"Uldbjerg","year":"2025","journal-title":"Sci. Total Environ."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s40618-022-01983-4","article-title":"Endocrine-Disrupting Chemicals (EDCs) and Cancer: New Perspectives on an Old Relationship","volume":"46","author":"Modica","year":"2022","journal-title":"J. Endocrinol. Invest."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"116458","DOI":"10.1016\/j.envpol.2021.116458","article-title":"Serum Polychlorinated Biphenyl (PCB) Levels and Risk of Testicular Germ Cell Tumors: A Population-Based Case-Control Study in Connecticut and Massachusetts","volume":"273","author":"Cheng","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"107014","DOI":"10.1016\/j.dib.2021.107014","article-title":"Dataset of Testicular Germ Cell Tumors (TGCT) Risk Associated with Serum Polychlorinated Biphenyl (PCB) by Age at Diagnosis and Histologic Types","volume":"36","author":"Cheng","year":"2021","journal-title":"Data Brief"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"109762","DOI":"10.1016\/j.envint.2025.109762","article-title":"Exposure to Per- and Polyfluoroalkyl Substances during Fetal Development and Risk of Testicular Germ Cell Cancer in Adulthood","volume":"203","author":"Uldbjerg","year":"2025","journal-title":"Environ. Int."},{"key":"ref_236","first-page":"e4834","article-title":"Endocrine Disrupting Chemicals and Risk of Testicular Cancer: A Systematic Review and Meta-Analysis","volume":"106","author":"Lim","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2605.2007.00837.x","article-title":"Phthalates: Metabolism and Exposure","volume":"31","author":"Wittassek","year":"2008","journal-title":"Int. J. Androl."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1289\/ehp.1408989","article-title":"Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes","volume":"123","author":"Rochester","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.3390\/ijerph8062265","article-title":"Effect of Endocrine Disruptor Pesticides: A Review","volume":"8","author":"Mnif","year":"2011","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1289\/ehp.1002211","article-title":"Intrinsic Human Elimination Half-Lives of Polychlorinated Biphenyls Derived from the Temporal Evolution of Cross-Sectional Biomonitoring Data from the United Kingdom","volume":"119","author":"Ritter","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A Review of the Pathways of Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Present Understanding of Health Effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1289\/ehp.1104711","article-title":"Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption","volume":"120","author":"Heger","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"ref_243","first-page":"288ra80","article-title":"Prolonged Exposure to Acetaminophen Reduces Testosterone Production by the Human Fetal Testis in a Xenograft Model","volume":"7","author":"Macdonald","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13293-025-00753-0","article-title":"Genetic Variants (LhcgrW495X\/+) and Environmental Toxicants (DEHP) Synergistically Induce DSD by Interfering with Steroidogenic Gene Expression","volume":"16","author":"Qigen","year":"2025","journal-title":"Biol. 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