{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:31:46Z","timestamp":1769581906235,"version":"3.49.0"},"reference-count":198,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T00:00:00Z","timestamp":1604793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1142481"],"award-info":[{"award-number":["APP1142481"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing incidence of testicular dysgenesis syndrome-related conditions and overall decline in human fertility has been linked to the prevalence of oestrogenic endocrine disrupting chemicals (EDCs) in the environment. Ectopic activation of oestrogen signalling by EDCs in the gonad can impact testis and ovary function and development. Oestrogen is the critical driver of ovarian differentiation in non-mammalian vertebrates, and in its absence a testis will form. In contrast, oestrogen is not required for mammalian ovarian differentiation, but it is essential for its maintenance, illustrating it is necessary for reinforcing ovarian fate. Interestingly, exposure of the bi-potential gonad to exogenous oestrogen can cause XY sex reversal in marsupials and this is mediated by the cytoplasmic retention of the testis-determining factor SOX9 (sex-determining region Y box transcription factor 9). Oestrogen can similarly suppress SOX9 and activate ovarian genes in both humans and mice, demonstrating it plays an essential role in all mammals in mediating gonad somatic cell fate. Here, we review the molecular control of gonad differentiation and explore the mechanisms through which exogenous oestrogen can influence somatic cell fate to disrupt gonad development and function. Understanding these mechanisms is essential for defining the effects of oestrogenic EDCs on the developing gonads and ultimately their impacts on human reproductive health.<\/jats:p>","DOI":"10.3390\/ijms21218377","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T19:03:37Z","timestamp":1604862217000},"page":"8377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-4019","authenticated-orcid":false,"given":"Melanie K.","family":"Stewart","sequence":"first","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deidre M.","family":"Mattiske","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Pask","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrg1381","article-title":"One tissue, two fates: Molecular genetic events that underlie testis versus ovary development","volume":"5","author":"Brennan","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.tig.2019.02.004","article-title":"Genetic control of gonadal sex determination and development","volume":"35","author":"Nef","year":"2019","journal-title":"Trends Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0960-0760(01)00158-3","article-title":"The ovarian phenotype of the aromatase knockout (ArKO) mouse","volume":"79","author":"Britt","year":"2001","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1093\/hmg\/ddn193","article-title":"Stabilization of \u03b2-catenin in XY gonads causes male-to-female sex-reversal","volume":"17","author":"Maatouk","year":"2008","journal-title":"Hum. Mol. Gen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/82652","article-title":"A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse","volume":"26","author":"Bishop","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/90046","article-title":"Sox9 induces testis development in XX transgenic mice","volume":"28","author":"Vidal","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1242\/dev.01087","article-title":"Functional analysis of Sox8 and Sox9 during sex determination in the mouse","volume":"131","author":"Chaboissier","year":"2004","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1095\/biolreprod.105.045930","article-title":"Homozygous inactivation of Sox9 causes complete XY sex reversal in mice","volume":"74","author":"Barrionuevo","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.cell.2009.11.021","article-title":"Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation","volume":"139","author":"Uhlenhaut","year":"2009","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1093\/hmg\/ddn016","article-title":"Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary","volume":"17","author":"Chassot","year":"2008","journal-title":"Hum. Mol. Gen."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Stewart, M.K., Mattiske, D.M., and Pask, A.J. (2020). Estrogen suppresses SOX9 and activates markers of female development in a human testis-derived cell line. BMC Mol. Cell Biol., 21.","DOI":"10.1186\/s12860-020-00307-9"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/1741-7007-8-113","article-title":"Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal","volume":"8","author":"Pask","year":"2010","journal-title":"BMC Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/S0140-6736(19)30690-7","article-title":"Populations, decreasing fertility, and reproductive health","volume":"393","author":"Skakkebaek","year":"2019","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal trends in sperm count: A systematic review and meta-regression analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1158\/1055-9965.2157.13.12","article-title":"Testicular cancer incidence in eight northern European countries: Secular and recent trends","volume":"13","author":"Richiardi","year":"2004","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1289\/ehp.99107297","article-title":"International trends in rates of hypospadias and cryptorchidism","volume":"107","author":"Paulozzi","year":"1999","journal-title":"Environ. Health Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1136\/adc.2006.112862","article-title":"Increasing prevalence of hypospadias in Western Australia, 1980\u20132000","volume":"92","author":"Nassar","year":"2007","journal-title":"Arch. Dis. Child."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000442975","article-title":"Global DSD update consortium global disorders of sex development update since 2006: Perceptions, approach and care","volume":"85","author":"Lee","year":"2016","journal-title":"Horm. Res. Paediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1093\/humrep\/16.5.972","article-title":"Testicular dysgenesis syndrome: An increasingly common developmental disorder with environmental aspects","volume":"16","author":"Skakkebaek","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1365-2265.2009.03545.x","article-title":"Testicular dysgenesis syndrome: Foetal origin of adult reproductive problems","volume":"71","author":"Veje","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1136\/archdischild-2015-308809","article-title":"Prevalence, repairs and complications of hypospadias: An Australian population-based study","volume":"100","author":"Schneuer","year":"2015","journal-title":"Arch. Dis. Child."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1556\/OH.2014.29858","article-title":"Prevalence and possible causes of hypospadias","volume":"155","author":"Sagodi","year":"2014","journal-title":"Orv. Hetil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1530\/rep.1.00025","article-title":"Environmental anti-androgens and male reproductive health: Focus on phthalates and testicular dysgenesis syndrome","volume":"127","author":"Fisher","year":"2004","journal-title":"Reproduction"},{"key":"ref_24","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. Part A Clin. Mol. Teratol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-069X-10-3","article-title":"Parental occupational exposure to endocrine disrupting chemicals and male genital malformations: A study in the Danish National Birth Cohort study","volume":"10","author":"Toft","year":"2011","journal-title":"Environ. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.eururo.2015.05.008","article-title":"Is hypospadias associated with prenatal exposure to endocrine disruptors? A French collaborative controlled study of a cohort of 300 consecutive children without genetic defect","volume":"68","author":"Kalfa","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_27","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":"2015","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12940-016-0161-9","article-title":"National birth defects prevention study hypospadias and maternal exposure to atrazine via drinking water in the national birth defects prevention study","volume":"15","author":"Winston","year":"2016","journal-title":"Environ. Health"},{"key":"ref_29","unstructured":"Damstra, T., Barlow, S., Bergman, A., Kavlock, R., and Van Der Kraak, G. (2002). Global Assessment of the State-of-the-Science of Endocrine Disruptors, World Health Organisation."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-disrupting chemicals: An endocrine society scientific statement","volume":"30","author":"Bourguignon","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_31","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":"Josh","year":"2014","journal-title":"Mol. Simul."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.tox.2005.02.002","article-title":"Differential effects of phthalate esters on transcriptional activities via human estrogen receptors \u03b1 and \u03b2, and androgen receptor","volume":"210","author":"Takeuchi","year":"2005","journal-title":"Toxicology"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.mce.2013.09.008","article-title":"Fetal programming of sexual development and reproductive function","volume":"382","author":"Zambrano","year":"2014","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.diff.2019.09.001","article-title":"A loss of estrogen signaling in the aromatase deficient mouse penis results in mild hypospadias","volume":"109","author":"Cripps","year":"2019","journal-title":"Differentiation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1096\/fj.201802586RR","article-title":"A critical role for estrogen signaling in penis development","volume":"33","author":"Govers","year":"2019","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0925-4773(98)00223-8","article-title":"Expression of estrogen receptor alpha and beta during mouse embryogenesis","volume":"81","author":"Lemmen","year":"1999","journal-title":"Mech. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1210\/jc.2010-2618","article-title":"Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary","volume":"96","author":"Fowler","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00418-014-1216-z","article-title":"Expression pattern of estrogen receptors \u03b1 and \u03b2 and G-protein-coupled estrogen receptor 1 in the human testis","volume":"142","author":"Fietz","year":"2014","journal-title":"Histochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e61726","DOI":"10.1371\/journal.pone.0061726","article-title":"Diethylstilboestrol exposure does not reduce testosterone production in human fetal testis xenografts","volume":"8","author":"Mitchell","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1093\/biolre\/ioy142","article-title":"In utero exposure to both high- and low-dose diethylstilbestrol disrupts mouse genital tubercle development","volume":"99","author":"Stewart","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.diff.2014.09.005","article-title":"Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains","volume":"88","author":"Mahawong","year":"2014","journal-title":"Differentiation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00204-018-2350-5","article-title":"Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders","volume":"93","author":"Schwartz","year":"2019","journal-title":"Arch Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/andr.12156","article-title":"Anogenital distance as a marker of androgen exposure in humans","volume":"4","author":"Thankamony","year":"2016","journal-title":"Andrology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"N\u2019Tumba-Byn, T., Moison, D., Lacroix, M., Lecureuil, C., Lesage, L., Prud\u2019homme, S.M., Pozzi-Gaudin, S., Frydman, R., Benachi, A., and Livera, G. (2012). Differential effects of bisphenol a and diethylstilbestrol on human, rat and mouse fetal Leydig cell function. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051579"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1093\/humrep\/dex093","article-title":"Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis","volume":"32","author":"Gaudriault","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.metabol.2018.03.022","article-title":"Endocrine disruptors and testicular function","volume":"86","author":"Lymperi","year":"2018","journal-title":"Metabolism"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/aje\/kws591","article-title":"The national birth defects prevention study hypospadias and maternal intake of phytoestrogens","volume":"178","author":"Carmichael","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mce.2011.01.006","article-title":"Hypospadias: Interactions between environment and genetics","volume":"335","author":"Kalfa","year":"2011","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1289\/ehp.1307309","article-title":"Urinary bisphenol A levels in young men: Association with reproductive hormones and semen quality","volume":"122","author":"Lassen","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"625.e304","DOI":"10.1016\/j.fertnstert.2010.09.026","article-title":"Urine bisphenol-A (BPA) level in relation to semen quality","volume":"95","author":"Li","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39931","DOI":"10.1038\/srep39931","article-title":"Effects of elevated \u03b2-estradiol levels on the functional morphology of the testis\u2014New insights","volume":"7","author":"Leavy","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.urology.2019.06.034","article-title":"Effects of estrogen on spermatogenesis in transgender women","volume":"132","author":"Jiang","year":"2019","journal-title":"Urology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.diff.2018.09.001","article-title":"Development of the human female reproductive tract","volume":"103","author":"Cunha","year":"2018","journal-title":"Differentiation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrendo.2017.36","article-title":"Environmental influences on ovarian dysgenesis\u2014developmental windows sensitive to chemical exposures","volume":"13","author":"Johansson","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1093\/humrep\/dei398","article-title":"Hypospadias: A transgenerational effect of diethylstilbestrol?","volume":"21","author":"Brouwers","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_58","unstructured":"IARC Pharmaceuticals (2012). A Review of Human Carcinogens, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans\/World Health Organization\/International Agency for Research on Cancer."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.reprotox.2017.04.009","article-title":"Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring","volume":"71","author":"Jishi","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"778","DOI":"10.7326\/0003-4819-122-10-199505150-00008","article-title":"Diethylstilbestrol revisited: A review of the long-term health effects","volume":"122","author":"Giusti","year":"1995","journal-title":"Ann. Intern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jpag.2018.05.002","article-title":"Age of menarche in a longitudinal US cohort","volume":"31","author":"Biro","year":"2018","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e20170085","DOI":"10.1542\/peds.2017-0085","article-title":"Secular trend of age at menarche in chinese adolescents born from 1973 to 2004","volume":"140","author":"Meng","year":"2017","journal-title":"Pediatrics"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Pathak, P.K., Tripathi, N., and Subramanian, S.V. (2014). Secular trends in menarcheal age in India-evidence from the Indian human development survey. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111027"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e932","DOI":"10.1542\/peds.2008-2491","article-title":"Recent decline in age at breast development: The Copenhagen puberty study","volume":"123","author":"Aksglaede","year":"2009","journal-title":"Pediatrics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101300","DOI":"10.1016\/j.beem.2019.101300","article-title":"Endocrine disrupters and possible contribution to pubertal changes","volume":"33","author":"Fudvoye","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s11154-016-9326-7","article-title":"Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs)","volume":"16","author":"Palioura","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1095\/biolreprod.115.130336","article-title":"Effects of endocrine-disrupting chemicals on the ovary","volume":"93","author":"Patel","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s00018-019-03028-1","article-title":"Establishment and depletion of the ovarian reserve: Physiology and impact of environmental chemicals","volume":"76","author":"Ge","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/CLEP.S37559","article-title":"Epidemiology, diagnosis, and management of polycystic ovary syndrome","volume":"6","author":"Sirmans","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/13697137.2019.1574738","article-title":"The global prevalence of primary ovarian insufficiency and early menopause: A meta-analysis","volume":"22","author":"Golezar","year":"2019","journal-title":"Climacteric"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/oxfordjournals.epirev.a036194","article-title":"Menopause: Its epidemiology and potential association with chronic diseases","volume":"17","author":"Sowers","year":"1995","journal-title":"Epidemiol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/BF00296207","article-title":"Risk for developing osteoporosis in untreated premature menopause","volume":"51","author":"Bagur","year":"1992","journal-title":"Calcif. Tissue Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1096\/fj.01-0992com","article-title":"Estrogen regulates development of the somatic cell phenotype in the eutherian ovary","volume":"16","author":"Britt","year":"2002","journal-title":"FASEB J."},{"key":"ref_74","first-page":"R143","article-title":"Do prenatal exposures pose a real threat to ovarian function? Bisphenol A as a case study","volume":"157","author":"Mathew","year":"2019","journal-title":"Reproduction"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E480","DOI":"10.1210\/jc.2010-1658","article-title":"Endocrine disruptors and polycystic ovary syndrome (PCOS): Elevated serum levels of bisphenol A in women with PCOS","volume":"96","author":"Kandaraki","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1289\/ehp.0901257","article-title":"Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats","volume":"118","author":"Bourguignon","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.taap.2014.02.009","article-title":"In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse","volume":"276","author":"Wang","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.reprotox.2016.03.045","article-title":"Perinatal exposure to mixtures of endocrine disrupting chemicals reduces female rat follicle reserves and accelerates reproductive aging","volume":"61","author":"Johansson","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1002\/jemt.22117","article-title":"Genistein affects ovarian folliculogenesis: A stereological study","volume":"75","year":"2012","journal-title":"Microsc. Res. Tech."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.taap.2013.04.028","article-title":"Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles","volume":"271","author":"Peretz","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.toxlet.2012.01.020","article-title":"Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines","volume":"210","author":"Watanabe","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jsbmb.2006.06.021","article-title":"Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells","volume":"101","author":"Rice","year":"2006","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000450972","article-title":"Sex reversal in reptiles: Reproductive oddity or powerful driver of evolutionary change?","volume":"10","author":"Holleley","year":"2016","journal-title":"Sex Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000448797","article-title":"Sex reversal in amphibians","volume":"10","author":"Flament","year":"2016","journal-title":"Sex Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1159\/000448365","article-title":"Sex reversal in birds","volume":"10","author":"Major","year":"2016","journal-title":"Sex Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2108\/zsj.22.1163","article-title":"Sex reversal in the medaka Oryzias latipes by brief exposure of early embryos to estradiol-17\u03b2","volume":"22","author":"Kobayashi","year":"2005","journal-title":"Zool. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1073\/pnas.41.9.669","article-title":"Experimental reversal of sex in the gonads of the opossum didelphis virginiana","volume":"41","author":"Burns","year":"1955","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1095\/biolreprod65.2.613","article-title":"Estrogen-induced gonadal sex reversal in the tammar wallaby","volume":"65","author":"Coveney","year":"2001","journal-title":"Biol. Reprod"},{"key":"ref_89","first-page":"274","article-title":"Molecular aspects of female and male gonadal development in mammals","volume":"1","author":"Pannetier","year":"2004","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_90","first-page":"567","article-title":"Characterization of ovine SRY transcript and developmental expression of genes involved in sexual differentiation","volume":"40","author":"Payen","year":"1996","journal-title":"Int. J. Dev. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1530\/rep.1.00704","article-title":"Oestrogen receptor alpha and beta, androgen receptor and progesterone receptor mRNA and protein localisation within the developing ovary and in small growing follicles of sheep","volume":"131","author":"Juengel","year":"2006","journal-title":"Reproduction"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.anireprosci.2009.05.004","article-title":"Development of the ovary and ontongeny of mRNA and protein for P450 aromatase (arom) and estrogen receptors (ER) \u03b1 and \u03b2 during early fetal life in cattle","volume":"117","author":"Garverick","year":"2010","journal-title":"Anim. Reprod. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1210\/endo.140.6.6823","article-title":"Targeted disruption of the estrogen receptor-alpha gene in female mice: Characterization of ovarian responses and phenotype in the adult","volume":"140","author":"Schomberg","year":"1999","journal-title":"Endocrinology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nrg.2017.60","article-title":"Vertebrate sex determination: Evolutionary plasticity of a fundamental switch","volume":"18","author":"Capel","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.chemosphere.2019.05.133","article-title":"A mechanism for the effect of endocrine disrupting chemicals on placentation","volume":"231","author":"Yang","year":"2019","journal-title":"Chemosphere"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/bs.ctdb.2019.01.002","article-title":"Characterizing the bipotential mammalian gonad","volume":"134","author":"Nef","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrendo.2014.163","article-title":"Genetic regulation of mammalian gonad development","volume":"10","author":"Eggers","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1101\/gad.228080.113","article-title":"Building the mammalian testis: Origins, differentiation, and assembly of the component cell populations","volume":"27","author":"Svingen","year":"2013","journal-title":"Genes Dev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1111\/andr.12107","article-title":"Cell-specific ablation in the testis: What have we learned?","volume":"3","author":"Smith","year":"2015","journal-title":"Andrology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1210\/en.2017-00196","article-title":"Sertoli cell number defines and predicts germ and Leydig cell population sizes in the adult mouse testis","volume":"158","author":"Rebourcet","year":"2017","journal-title":"Endocrinology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1242\/dev.121.6.1603","article-title":"Expression of Sry, the mouse sex determining gene","volume":"121","author":"Hacker","year":"1995","journal-title":"Development"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/346240a0","article-title":"A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif","volume":"346","author":"Sinclair","year":"1990","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1242\/dev.029587","article-title":"A critical time window of Sry action in gonadal sex determination in mice","volume":"136","author":"Hiramatsu","year":"2008","journal-title":"Development"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1006\/dbio.1999.9436","article-title":"Sex reversal caused by Mus musculus domesticus Y chromosomes linked to variant expression of the testis-determining gene Sry","volume":"216","author":"Nagamine","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ng0996-62","article-title":"Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds","volume":"14","author":"Hacker","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/(SICI)1097-0177(200003)217:3<293::AID-DVDY7>3.0.CO;2-P","article-title":"Expression and subcellular localization of SF-1, SOX9, WT1, and AMH proteins during early human testicular development","volume":"217","author":"Moniot","year":"2000","journal-title":"Dev. Dyn."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1093\/hmg\/ddi133","article-title":"Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry","volume":"14","author":"Qin","year":"2005","journal-title":"Hum. Mol. Gen."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0092-8674(94)90041-8","article-title":"Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9","volume":"79","author":"Wagner","year":"1994","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/372525a0","article-title":"Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene","volume":"372","author":"Foster","year":"1994","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/(SICI)1097-0177(199909)216:1<72::AID-DVDY9>3.0.CO;2-9","article-title":"Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene","volume":"216","author":"Colvin","year":"1999","journal-title":"Dev. Dyn."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1242\/dev.01239","article-title":"Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination","volume":"131","author":"Schmahl","year":"2004","journal-title":"Development"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e187","DOI":"10.1371\/journal.pbio.0040187","article-title":"Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination","volume":"4","author":"Kim","year":"2006","journal-title":"PLoS Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0092-8674(01)00284-7","article-title":"Male-to-female sex reversal in mice lacking fibroblast growth factor 9","volume":"104","author":"Colvin","year":"2001","journal-title":"Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1093\/hmg\/ddv374","article-title":"FGFR2 mutation in 46,XY sex reversal with craniosynostosis","volume":"24","author":"Ono","year":"2015","journal-title":"Hum. Mol. Gen."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2005.08.039","article-title":"Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination","volume":"287","author":"Wilhelm","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10553","DOI":"10.1074\/jbc.M609578200","article-title":"SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development","volume":"282","author":"Wilhelm","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1242\/dev.129.5.1155","article-title":"Sexually dimorphic development of mouse primordial germ cells: Switching from oogenesis to spermatogenesis","volume":"129","author":"Adams","year":"2002","journal-title":"Development"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1242\/dev.032631","article-title":"The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation","volume":"136","author":"Moniot","year":"2009","journal-title":"Development"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1128\/MCB.18.11.6653","article-title":"Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-M\u00fcllerian hormone gene","volume":"18","author":"Bonneaud","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0092-8674(00)81527-5","article-title":"Targeted mutagenesis of the endogenous mouse Mis gene promoter: In vivo definition of genetic pathways of vertebrate sexual development","volume":"99","author":"Arango","year":"1999","journal-title":"Cell"},{"key":"ref_121","first-page":"1","article-title":"Anti-m\u00fcllerian hormone: The Jost factor","volume":"48","author":"Josso","year":"1993","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/345167a0","article-title":"Abnormal sexual development in transgenic mice chronically expressing M\u00fcllerian inhibiting substance","volume":"345","author":"Behringer","year":"1990","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/17068","article-title":"Female development in mammals is regulated by Wnt-4 signalling","volume":"397","author":"Vainio","year":"1999","journal-title":"Nature"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng1907","article-title":"R-spondin1 is essential in sex determination, skin differentiation and malignancy","volume":"38","author":"Parma","year":"2006","journal-title":"Nat. Genet"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4161\/cc.5.1.2305","article-title":"R-Spondin proteins: A novel link to beta-catenin activation","volume":"5","author":"Kim","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1242\/dev.024653","article-title":"Ovarian development in mice requires the GATA4-FOG2 transcription complex","volume":"135","author":"Manuylov","year":"2008","journal-title":"Development"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1242\/dev.00969","article-title":"The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance","volume":"131","author":"Schmidt","year":"2004","journal-title":"Development"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"17577","DOI":"10.1074\/jbc.M117.811349","article-title":"\u03b2-Catenin directs the transformation of testis Sertoli cells to ovarian granulosa-like cells by inducing Foxl2 expression","volume":"292","author":"Li","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1093\/hmg\/ddy312","article-title":"Genome-wide identification of FOXL2 binding and characterization of FOXL2 feminizing action in the fetal gonads","volume":"27","author":"Nicol","year":"2018","journal-title":"Hum. Mol. Gen."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/84781","article-title":"The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis\/ptosis\/epicanthus inversus syndrome","volume":"27","author":"Crisponi","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/ng769","article-title":"A 11.7-kb deletion triggers intersexuality and polledness in goats","volume":"29","author":"Pailhoux","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e85545","DOI":"10.7554\/eLife.04207","article-title":"The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells","volume":"3","author":"Georges","year":"2014","journal-title":"eLife"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8681","DOI":"10.1128\/MCB.24.19.8681-8690.2004","article-title":"Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2\/neu\/phosphatidylinositol 3-kinase\/Akt signaling pathway","volume":"24","author":"Guo","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/aps.2014.123","article-title":"Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology","volume":"36","author":"Ikeda","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng.730","article-title":"FOXA1 is a key determinant of estrogen receptor function and endocrine response","volume":"43","author":"Hurtado","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"10866","DOI":"10.1073\/pnas.1834480100","article-title":"Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1\/beta-catenin synergy","volume":"100","author":"Jordan","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1093\/hmg\/ddm235","article-title":"Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells","volume":"16","author":"Ottolenghi","year":"2007","journal-title":"Hum. Mol. Gen."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/j.biocel.2008.06.006","article-title":"Human SRY inhibits \u03b2-catenin-mediated transcription","volume":"40","author":"Bernard","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1074\/jbc.M808048200","article-title":"Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus","volume":"284","author":"Topol","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1210\/en.2011-1347","article-title":"Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer","volume":"153","author":"Bernard","year":"2012","journal-title":"Endocrinol"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1210\/jc.2013-3690","article-title":"Disorders of sex development (DSDs): An update","volume":"99","author":"Ostrer","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Bogani, D., Siggers, P., Brixey, R., Warr, N., Beddow, S., Edwards, J., Williams, D., Wilhelm, D., Koopman, P., and Flavell, R.A. (2009). Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) reveals a requirement for mapk signalling in mouse sex determination. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000196"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1128\/MCB.01435-06","article-title":"Activation of MTK1\/MEKK4 by GADD45 through induced N-C dissociation and dimerization-mediated trans autophosphorylation of the MTK1 kinase domain","volume":"27","author":"Miyake","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.devcel.2012.09.014","article-title":"GADD45G functions in male sex determination by promoting p38 signaling and sry expression","volume":"23","author":"Gierl","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.devcel.2012.09.016","article-title":"Gadd45\u03b3 and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression","volume":"23","author":"Warr","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Warr, N., Bogani, D., Siggers, P., Brixey, R., Tateossian, H., Dopplapudi, A., Wells, S., Cheeseman, M., Xia, Y., and Ostrer, H. (2011). Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019572"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/hmg\/ddt502","article-title":"Mutations in MAP3K1 tilt the balance from SOX9\/FGF9 to WNT\/beta-catenin signaling","volume":"23","author":"Loke","year":"2014","journal-title":"Hum. Mol. Gen."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.ajhg.2010.11.003","article-title":"Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination","volume":"87","author":"Pearlman","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1093\/hmg\/ddz002","article-title":"Mutations in MAP3K1 that cause 46,XY disorders of sex development disrupt distinct structural domains in the protein","volume":"28","author":"Chamberlin","year":"2019","journal-title":"Hum. Mol. Gen."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"587460","DOI":"10.1155\/2013\/587460","article-title":"The variety of vertebrate mechanisms of sex determination","volume":"2013","author":"Trukhina","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10577-011-9260-1","article-title":"A role for estrogen in somatic cell fate of the mammalian gonad","volume":"20","author":"Pask","year":"2012","journal-title":"Chromosome Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1093\/nar\/29.14.2905","article-title":"Estrogen receptor interaction with estrogen response elements","volume":"29","author":"Klinge","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1210\/me.2004-0486","article-title":"Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes","volume":"19","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1152\/physrev.2001.81.4.1535","article-title":"Mechanisms of estrogen action","volume":"81","author":"Nilsson","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.steroids.2017.11.001","article-title":"Experimental models for evaluating non-genomic estrogen signaling","volume":"133","author":"Stefkovich","year":"2018","journal-title":"Steroids"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fendo.2019.00224","article-title":"Molecular mechanisms and signaling pathways involved in Sertoli cell proliferation","volume":"10","author":"Meroni","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1359\/jbmr.2001.16.6.1045","article-title":"Mechanical strain and estrogen activate estrogen receptor alpha in bone cells","volume":"16","author":"Jessop","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1006\/bbrc.1997.6746","article-title":"Rapid activation of MAP kinase by estrogen in the bone cell line","volume":"235","author":"Endoh","year":"1997","journal-title":"Biochem. Biophys. Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1172\/JCI5347","article-title":"Estrogen receptor \u03b1 mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen","volume":"103","author":"Chen","year":"1999","journal-title":"J. Clin. Invest."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.1210\/endo.138.9.5489","article-title":"Rapid membrane effects of steroids in neuroblastoma cells: Effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription","volume":"138","author":"Watters","year":"1997","journal-title":"Endocrinology"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Stewart, M.K., Mattiske, D.M., and Pask, A.J. (2020). Oestrogen regulates SOX9 bioavailability by rapidly activating ERK1\/2 and stabilising microtubules in a human testis-derived cell line. Exp. Cell Res., (under review).","DOI":"10.1016\/j.yexcr.2020.112405"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/bs.acr.2018.02.004","article-title":"Extracellular-regulated kinases: Signaling from RAS to ERK substrates to control biological outcomes","volume":"138","author":"Eblen","year":"2018","journal-title":"Adv. Cancer Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000505799","article-title":"Transcriptomic analysis of MAP3K1 and MAP3K4 in the developing marsupial gonad","volume":"13","author":"Paranjpe","year":"2019","journal-title":"Sex Dev."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/biolre\/ioz090","article-title":"Mice lacking membrane estrogen receptor 1 are protected from reproductive pathologies resulting from developmental estrogen exposure","volume":"101","author":"Nanjappa","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Varea, O., Garrido, J.J., Dopazo, A., Mendez, P., Garcia-Segura, L.M., and Wandosell, F. (2009). Estradiol activates beta-catenin dependent transcription in neurons. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005153"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"40255","DOI":"10.1074\/jbc.C400331200","article-title":"Wnt\/beta-catenin and estrogen signaling converge in vivo","volume":"279","author":"Kouzmenko","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.mcn.2003.10.008","article-title":"Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus","volume":"25","author":"Avila","year":"2004","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"11221","DOI":"10.1074\/jbc.M611871200","article-title":"Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity","volume":"282","author":"Fang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"43363","DOI":"10.1074\/jbc.M304363200","article-title":"Raloxifene inhibits estrogen-induced up-regulation of telomerase activity in a human breast cancer cell line","volume":"278","author":"Kawagoe","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jsbmb.2017.03.005","article-title":"GPER modulators: Opportunity Nox on the heels of a class Akt","volume":"176","author":"Prossnitz","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1126\/science.1106943","article-title":"A transmembrane intracellular estrogen receptor mediates rapid cell signaling","volume":"307","author":"Revankar","year":"2005","journal-title":"Science"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"9971","DOI":"10.1074\/jbc.M508778200","article-title":"Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase","volume":"281","author":"Taurin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_173","first-page":"a011148","article-title":"The cyclic AMP pathway","volume":"4","year":"2012","journal-title":"Cold. Spring Harb. Perspect Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"8517","DOI":"10.1073\/pnas.91.18.8517","article-title":"Estrogen action via the cAMP signaling pathway: Stimulation of adenylate cyclase and cAMP-regulated gene transcription","volume":"91","author":"Aronica","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1093\/nar\/gkw522","article-title":"LSD1 engages a corepressor complex for the activation of the estrogen receptor \u03b1 by estrogen and cAMP","volume":"44","author":"Bennesch","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gad.568410","article-title":"CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP","volume":"24","author":"Carascossa","year":"2010","journal-title":"Genes Dev."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/onc.2011.294","article-title":"A Rac1\/PAK1 cascade controls \u03b2-catenin activation in colon cancer cells","volume":"31","author":"Zhu","year":"2012","journal-title":"Oncogene"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S0014-5793(02)03846-2","article-title":"Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells","volume":"535","author":"Mazumdar","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gene.2017.12.039","article-title":"Cloning and functional characterization of human Pak1 promoter by steroid hormones","volume":"646","author":"Raghavan","year":"2018","journal-title":"Gene"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"144812","DOI":"10.1016\/j.gene.2020.144812","article-title":"Molecular insights into hormone regulation via signaling pathways in Sertoli cells: With discussion on infertility and testicular tumor","volume":"753","author":"Ni","year":"2020","journal-title":"Gene"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ydbio.2010.02.010","article-title":"Estrogen represses SOX9 during sex determination in the red-eared slider turtle Trachemys scripta","volume":"341","author":"Barske","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Lambeth, L.S., Cummins, D.M., Doran, T.J., Sinclair, A.H., and Smith, C.A. (2013). Overexpression of aromatase alone is sufficient for ovarian development in genetically male chicken embryos. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068362"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ygcen.2013.05.013","article-title":"Neonatal expression of amh, sox9 and sf-1 mRNA in Caiman latirostris and effects of in ovo exposure to endocrine disrupting chemicals","volume":"191","author":"Durando","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.tem.2008.04.002","article-title":"Boys, girls and shuttling of SRY and SOX9","volume":"19","author":"Sim","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1186\/s13046-019-1236-6","article-title":"FGFs\/FGFRs-dependent signalling in regulation of steroid hormone receptors\u2014implications for therapy of luminal breast cancer","volume":"38","author":"Piasecka","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1210\/me.2003-0441","article-title":"Genome-wide identification of high-affinity estrogen response elements in human and mouse","volume":"18","author":"Bourdeau","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"E1649","DOI":"10.1210\/jc.2011-3133","article-title":"Differential regulation of ovarian anti-m\u00fcllerian hormone (AMH) by estradiol through \u03b1- and \u03b2-estrogen receptors","volume":"97","author":"Grynberg","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/molehr\/gah015","article-title":"Anti-M\u00fcllerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic follicle recruitment","volume":"10","author":"Weenen","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1210\/endo.143.3.8691","article-title":"Anti-M\u00fcllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary","volume":"143","author":"Durlinger","year":"2002","journal-title":"Endocrinology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.envpol.2018.12.006","article-title":"In utero exposure to bisphenol A disrupts fetal testis development in rats","volume":"246","author":"Lv","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1095\/biolreprod.114.120907","article-title":"Disruption of rat testis development following combined in utero exposure to the phytoestrogen genistein and antiandrogenic plasticizer di-(2-ethylhexyl) phthalate","volume":"91","author":"Jones","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1210\/en.2008-1311","article-title":"Increased exposure to estrogens disturbs maturation, steroidogenesis, and cholesterol homeostasis via estrogen receptor alpha in adult mouse Leydig cells","volume":"150","author":"Strauss","year":"2009","journal-title":"Endocrinology"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e79437","DOI":"10.1371\/journal.pone.0079437","article-title":"Microarray analysis of perinatal-estrogen-induced changes in gene expression related to brain sexual differentiation in mice","volume":"8","author":"Sakakibara","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-13060-1","article-title":"RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2","volume":"10","author":"Nicol","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.diff.2016.11.002","article-title":"Beta-catenin and estrogen signaling collaborate to drive cyclin D1 expression in developing mouse prostate","volume":"93","author":"Mulligan","year":"2017","journal-title":"Differentiation"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1210\/me.2007-0445","article-title":"Cooperative control via lymphoid enhancer factor 1\/T cell factor 3 and estrogen receptor-\u03b1 for uterine gene regulation by estrogen","volume":"22","author":"Ray","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms10751","article-title":"RUNX1 prevents oestrogen-mediated AXIN1 suppression and \u03b2-catenin activation in ER-positive breast cancer","volume":"7","author":"Chimge","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1267\/ahc.09033","article-title":"The expression of Wnt4 is regulated by estrogen via an estrogen receptor alpha-dependent pathway in rat pituitary growth hormone-producing cells","volume":"42","author":"Miyakoshi","year":"2009","journal-title":"Acta Histochem. Cytochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:30:47Z","timestamp":1760178647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,8]]},"references-count":198,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21218377"],"URL":"https:\/\/doi.org\/10.3390\/ijms21218377","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,8]]}}}