{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:09:59Z","timestamp":1788869399086,"version":"build-2803163510"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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>Infertility affects approximately one in six individuals worldwide and is a highly heterogeneous disorder resulting from the complex interplay of genetic, epigenetic, endocrine, environmental and lifestyle factors. Although numerous genes and molecular pathways involved in female and male infertility have been identified, elucidating the functional consequences of disease-associated variants remains challenging due to the lack of relevant human experimental models. In recent years, reproductive organoids have emerged as powerful three-dimensional systems that recapitulate key structural, cellular and functional characteristics of the ovary, fallopian tube, endometrium, testis and early embryo. Here, we review the current landscape of reproductive organoid models based on a focused analysis of the literature, with particular emphasis on original studies describing their generation, characterization and applications. Beyond modeling tissue development and reproductive physiology, these models provide unique opportunities to investigate infertility-associated mechanisms, gene regulatory networks, cell\u2013cell communication and tissue-specific responses to environmental and pharmacological stimuli. Single-cell and spatial transcriptomics, multi-omics, CRISPR\/Cas9 genome editing, artificial intelligence and bioengineering technologies, including organ-on-chip systems, are expanding their potential as next-generation platforms for functional genomics, disease modeling, biomarker discovery and therapeutic screening. However, current reproductive organoids remain simplified representations of native tissues, with limitations in physiological maturity, reproducibility and standardization, while their clinical predictive value remains to be established. Overall, by linking genomic variation with molecular regulation, cellular phenotypes and tissue organization, reproductive organoids represent promising preclinical platforms for understanding human infertility and may ultimately contribute to the development of precision reproductive medicine.<\/jats:p>","DOI":"10.3390\/genes17091080","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:23:51Z","timestamp":1788866631000},"page":"1080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Next-Generation Reproductive Organoids with Genomics, Multi-Omics and Bioengineering to Understand Human Infertility"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2421-5676","authenticated-orcid":false,"given":"Paul","family":"Barreau","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine and Biotherapy (IRMB), University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7666-9024","authenticated-orcid":false,"given":"Cyril","family":"Djari","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-4130","authenticated-orcid":false,"given":"John","family":"De Vos","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine and Biotherapy (IRMB), University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-4369","authenticated-orcid":false,"given":"Nino-Guy","family":"Cassuto","sequence":"additional","affiliation":[{"name":"ART Unit, Drouot Laboratory, 75009 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-7995","authenticated-orcid":false,"given":"Said","family":"Assou","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine and Biotherapy (IRMB), University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"hoac051","DOI":"10.1093\/hropen\/hoac051","article-title":"Infertility Prevalence and the Methods of Estimation from 1990 to 2021: A Systematic Review and Meta-Analysis","volume":"2022","author":"Cox","year":"2022","journal-title":"Hum. Reprod. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1093\/humrep\/deag029","article-title":"The International Glossary on Infertility and Fertility Care, 2025\u2020","volume":"41","author":"Dyer","year":"2026","journal-title":"Hum. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Martinovi\u0107, L.S., Mladeni\u0107, T., Lovri\u0107, D., Ostoji\u0107, S., and Devi\u0107 Pavli\u0107, S. (2024). Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies. Epigenomes, 8.","DOI":"10.3390\/epigenomes8030034"},{"key":"ref_4","first-page":"623","article-title":"Infertility: Evaluation and Management","volume":"107","author":"Phillips","year":"2023","journal-title":"Am. Fam. Physician"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shan, J., Li, D.-J., and Wang, X.-Q. (2023). Towards a Better Understanding of Endometriosis-Related Infertility: A Review on How Endometriosis Affects Endometrial Receptivity. Biomolecules, 13.","DOI":"10.3390\/biom13030430"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of Male Infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male Infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13048-023-01151-z","article-title":"Mechanisms of Ovarian Aging in Women: A Review","volume":"16","author":"Wang","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_9","first-page":"176","article-title":"Association between Nondisjunction and Maternal Age in Meiosis-II Human Oocytes","volume":"59","author":"Dailey","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s11154-022-09759-0","article-title":"Reproductive Axis Ageing and Fertility in Men","volume":"23","author":"Anderson","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/OGX.0000000000000043","article-title":"Definition and Epidemiology of Unexplained Infertility","volume":"69","author":"Gelbaya","year":"2014","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.fertnstert.2010.09.043","article-title":"Comparison of Multiple Psychological Distress Measures between Men and Women Preparing for in Vitro Fertilization","volume":"95","author":"Wichman","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101594","DOI":"10.1016\/j.beem.2021.101594","article-title":"Genetics of Ovarian Insufficiency and Defects of Folliculogenesis","volume":"36","author":"Mendonca","year":"2022","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1210\/jc.2019-00248","article-title":"Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease","volume":"104","author":"Jolly","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/humupd\/dmv036","article-title":"Genetics of Primary Ovarian Insufficiency: New Developments and Opportunities","volume":"21","author":"Qin","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/cge.13803","article-title":"An Exome-Wide Exploration of Cases of Primary Ovarian Insufficiency Uncovers Novel Sequence Variants and Candidate Genes","volume":"98","author":"Todeschini","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bpobgyn.2018.01.012","article-title":"Genetics of Endometriosis: State of the Art on Genetic Risk Factors for Endometriosis","volume":"50","author":"Fung","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/GCO.0000000000000695","article-title":"Genetics of Recurrent Pregnancy Loss: A Review","volume":"33","author":"Tise","year":"2021","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20230127","DOI":"10.1590\/1678-4685-gmb-2023-0127","article-title":"From Bench to in Silico and Backwards: What Have We Done on Genetics of Recurrent Pregnancy Loss and Implantation Failure and Where Should We Go Next?","volume":"46","author":"Gomes","year":"2024","journal-title":"Genet. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/ng.2445","article-title":"Genome-Wide Association Meta-Analysis Identifies New Endometriosis Risk Loci","volume":"44","author":"Nyholt","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12958-018-0330-5","article-title":"Genetics of the Human Y Chromosome and Its Association with Male Infertility","volume":"16","author":"Colaco","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/MOU.0000000000001287","article-title":"Genetics of Male Infertility","volume":"35","author":"Corsini","year":"2025","journal-title":"Curr. Opin. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1056\/NEJM199702203360802","article-title":"Microdeletions in the Y Chromosome of Infertile Men","volume":"336","author":"Pryor","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12958-020-00621-z","article-title":"Organoid Technology in Female Reproductive Biomedicine","volume":"18","author":"Esfandiari","year":"2020","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s12015-020-10039-0","article-title":"Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery","volume":"16","author":"Cui","year":"2020","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R103","DOI":"10.1530\/REP-20-0499","article-title":"Organoids as Tools to Investigate the Molecular Mechanisms of Male Infertility and Its Treatments","volume":"161","author":"Kanbar","year":"2021","journal-title":"Reproduction"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8989","DOI":"10.1038\/ncomms9989","article-title":"The Notch and Wnt Pathways Regulate Stemness and Differentiation in Human Fallopian Tube Organoids","volume":"6","author":"Kessler","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/ncb3516","article-title":"Long-Term, Hormone-Responsive Organoid Cultures of Human Endometrium in a Chemically Defined Medium","volume":"19","author":"Turco","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.stemcr.2016.11.012","article-title":"Primary Human Testicular Cells Self-Organize into Organoids with Testicular Properties","volume":"8","author":"Baert","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-16-0302","article-title":"Oviduct: Roles in Fertilization and Early Embryo Development","volume":"232","author":"Li","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0889-8529(05)70044-X","article-title":"Female Infertility","volume":"27","author":"Hull","year":"1998","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bpobgyn.2022.03.003","article-title":"Menopause Transition: Physiology and Symptoms","volume":"81","author":"Talaulikar","year":"2022","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/humrep\/dem408","article-title":"A New Model of Reproductive Aging: The Decline in Ovarian Non-Growing Follicle Number from Birth to Menopause","volume":"23","author":"Hansen","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wallace, W.H.B., and Kelsey, T.W. (2010). Human Ovarian Reserve from Conception to the Menopause. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008772"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ishizuka, B. (2021). Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI). Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.626924"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e83291","DOI":"10.7554\/eLife.83291","article-title":"Directed Differentiation of Human iPSCs to Functional Ovarian Granulosa-like Cells via Transcription Factor Overexpression","volume":"12","author":"Kramme","year":"2023","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1038\/s41467-017-01851-3","article-title":"In Vivo Transplantation of 3D Encapsulated Ovarian Constructs in Rats Corrects Abnormalities of Ovarian Failure","volume":"8","author":"Sittadjody","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/s41467-019-09144-7","article-title":"Chronic Chlamydia Infection in Human Organoids Increases Stemness and Promotes Age-Dependent CpG Methylation","volume":"10","author":"Kessler","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s43032-023-01350-5","article-title":"Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids","volume":"31","author":"Yu","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e76721","DOI":"10.7554\/eLife.76721","article-title":"C-Myc Plays a Key Role in IFN-\u03b3-Induced Persistence of Chlamydia Trachomatis","volume":"11","author":"Vollmuth","year":"2022","journal-title":"eLife"},{"key":"ref_41","first-page":"3935","article-title":"Endometrial Membrane Organoids from Human Embryonic Stem Cell Combined with the 3D Matrigel for Endometrium Regeneration in Asherman Syndrome","volume":"6","author":"Jiang","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"954","DOI":"10.7150\/thno.90538","article-title":"Endometrial Organoids: A Reservoir of Functional Mitochondria for Uterine Repair","volume":"14","author":"Hwang","year":"2024","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/s41556-019-0360-z","article-title":"Patient-Derived Organoids from Endometrial Disease Capture Clinical Heterogeneity and Are Amenable to Drug Screening","volume":"21","author":"Boretto","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12958-025-01377-0","article-title":"FOXL2 Drives the Differentiation of Supporting Gonadal Cells in Early Ovarian Development","volume":"23","author":"Danti","year":"2025","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1097\/00003081-198012000-00023","article-title":"Anatomy and Physiology of the Fallopian Tube","volume":"23","author":"Eddy","year":"1980","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"254","DOI":"10.23736\/S0031-0808.21.04421-9","article-title":"Study on the Efficacy and Safety of Fallopian Tube Interventional Recanalization in the Treatment of Tubal Obstructive Infertility","volume":"65","author":"Shen","year":"2023","journal-title":"Panminerva Medica"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11010-021-04270-7","article-title":"Fallopian Tubal Infertility: The Result of Chlamydia Trachomatis-Induced Fallopian Tubal Fibrosis","volume":"477","author":"Ling","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1152\/physrev.00031.2019","article-title":"Physiology of the Endometrium and Regulation of Menstruation","volume":"100","author":"Critchley","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2147\/IJWH.S165474","article-title":"Asherman\u2019s Syndrome: Current Perspectives on Diagnosis and Management","volume":"11","author":"Dreisler","year":"2019","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00404-007-0419-0","article-title":"Genital Tuberculosis: An Important Cause of Asherman\u2019s Syndrome in India","volume":"277","author":"Sharma","year":"2008","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.tjog.2022.08.002","article-title":"Endometriosis: Part I. Basic Concept","volume":"61","author":"Wang","year":"2022","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1242\/dev.148478","article-title":"Development of Organoids from Mouse and Human Endometrium Showing Endometrial Epithelium Physiology and Long-Term Expandability","volume":"144","author":"Boretto","year":"2017","journal-title":"Development"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2208040119","DOI":"10.1073\/pnas.2208040119","article-title":"Bovine and Human Endometrium-Derived Hydrogels Support Organoid Culture from Healthy and Cancerous Tissues","volume":"119","author":"Jamaluddin","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/B978-0-444-63247-0.00003-1","article-title":"Anatomy and Physiology of Genital Organs-Men","volume":"130","author":"Clement","year":"2015","journal-title":"Handb. Clin. Neurol."},{"key":"ref_55","first-page":"46","article-title":"Prevalence of male infertility in a university hospital in Morocco","volume":"38","author":"Frikh","year":"2021","journal-title":"Pan Afr. Med. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biomaterials.2017.03.025","article-title":"Testicular Organoid Generation by a Novel in Vitro Three-Layer Gradient System","volume":"130","author":"Stukenborg","year":"2017","journal-title":"Biomaterials"},{"key":"ref_57","first-page":"1","article-title":"Spermatogenesis","volume":"13","author":"Loveland","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.gyobfe.2005.07.014","article-title":"Aging and spermatogenesis: An histologic, cytogenetic and apoptosis study","volume":"33","author":"Dakouane","year":"2005","journal-title":"Gynecol. Obstet. Fertil."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/humrep\/deg107","article-title":"The Association of Age and Semen Quality in Healthy Men","volume":"18","author":"Eskenazi","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"62055","DOI":"10.1007\/s11356-021-16331-x","article-title":"The Mutagenic Effect of Tobacco Smoke on Male Fertility","volume":"29","author":"Omolaoye","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1093\/humrep\/deaf020","article-title":"The Major Phytocannabinoids, Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD), Affect the Function of CatSper Calcium Channels in Human Sperm","volume":"40","author":"Wehrli","year":"2025","journal-title":"Hum. Reprod."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4103\/1008-682X.172827","article-title":"Y-Chromosome Microdeletions in Nonobstructive Azoospermia and Severe Oligozoospermia","volume":"19","author":"Cunha","year":"2017","journal-title":"Asian J. Androl."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1406192","article-title":"X-Linked TEX11 Mutations, Meiotic Arrest, and Azoospermia in Infertile Men","volume":"372","author":"Yatsenko","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1111\/andr.13269","article-title":"Whole-Genome Sequencing Identifies New Candidate Genes for Nonobstructive Azoospermia","volume":"10","author":"Malcher","year":"2022","journal-title":"Andrology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"045024","DOI":"10.1088\/1758-5090\/ad618f","article-title":"Spermatogenesis in Mouse Testicular Organoids with Testis-Specific Architecture, Improved Germ Cell Survival and Testosterone Production","volume":"16","author":"Richer","year":"2024","journal-title":"Biofabrication"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"122980","DOI":"10.1016\/j.lfs.2024.122980","article-title":"Generation of Mouse Testicular Organoids with Highly Compartmentalized Tubular Lumen Structure and Their Cryopreservation","volume":"355","author":"Tan","year":"2024","journal-title":"Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sakib, S., Lara, N.D.L.E.M., Huynh, B.C., and Dobrinski, I. (2022). Organotypic Rat Testicular Organoids for the Study of Testicular Maturation and Toxicology. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.892342"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108645","DOI":"10.1016\/j.reprotox.2024.108645","article-title":"An in Vitro Testicular Organoid Model for the Study of Testis Morphogenesis, Somatic Cell Maturation, Endocrine Function, and Toxicological Assessment of Endocrine Disruptors","volume":"128","author":"Cham","year":"2024","journal-title":"Reprod. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.3724\/abbs.2022164","article-title":"Developing Rat Testicular Organoid Models for Assessing the Reproductive Toxicity of Antidepression Drugs in Vitro","volume":"54","author":"Wu","year":"2022","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/S0140-6736(03)14845-3","article-title":"Azoospermia in Patients Heterozygous for a Mutation in SYCP3","volume":"362","author":"Miyamoto","year":"2003","journal-title":"Lancet"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.devcel.2021.12.022","article-title":"Early Human Embryonic Development: Blastocyst Formation to Gastrulation","volume":"57","author":"Rossant","year":"2022","journal-title":"Dev. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.devcel.2016.06.014","article-title":"Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency","volume":"38","author":"Wossidlo","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bulletti, F.M., Sciorio, R., Conforti, A., De Luca, R., Bulletti, C., Palagiano, A., Berrettini, M., Scaravelli, G., and Pierson, R.A. (2024). Causes of Embryo Implantation Failure: A Systematic Review and Metaanalysis of Procedures to Increase Embryo Implantation Potential. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1429193"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0015-0282(16)58291-0","article-title":"A New Method to Study the Process of Implantation of a Human Blastocyst in Vitro","volume":"65","author":"Landgren","year":"1996","journal-title":"Fertil. Steril."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41586-021-03356-y","article-title":"Blastocyst-like Structures Generated from Human Pluripotent Stem Cells","volume":"591","author":"Yu","year":"2021","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.stem.2021.04.031","article-title":"Naive Stem Cell Blastocyst Model Captures Human Embryo Lineage Segregation","volume":"28","author":"Yanagida","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41586-021-04267-8","article-title":"Human Blastoids Model Blastocyst Development and Implantation","volume":"601","author":"Kagawa","year":"2022","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.stem.2023.08.002","article-title":"Large-Scale Production of Human Blastoids Amenable to Modeling Blastocyst Development and Maternal-Fetal Cross Talk","volume":"30","author":"Yu","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_79","first-page":"337","article-title":"Modeling Human Pregastrulation Development by 3D Culture of Blastoids Generated from Primed-to-Na\u00efve Transitioning Intermediates","volume":"14","author":"Tu","year":"2023","journal-title":"Protein Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.stem.2024.12.010","article-title":"Modeling Early Gastrulation in Human Blastoids with DNA Methylation Patterns of Natural Blastocysts","volume":"32","author":"Xie","year":"2025","journal-title":"Cell Stem Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.ajog.2024.08.041","article-title":"Single-Cell Omics Technologies-Fundamentals on How to Create Single-Cell Looking Glasses for Reproductive Health","volume":"232","author":"Diop","year":"2025","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eadm7506","DOI":"10.1126\/sciadv.adm7506","article-title":"Cellular Atlas of the Human Ovary Using Morphologically Guided Spatial Transcriptomics and Single-Cell Sequencing","volume":"10","author":"Jones","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41467-025-67492-z","article-title":"Decrypting Spatiotemporal Code of Human Endometrial Receptivity","volume":"17","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/andr.70043","article-title":"Applications of Spatial Transcriptomics in Studying Spermatogenesis","volume":"13","author":"Xu","year":"2025","journal-title":"Andrology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1093\/bfgp\/elae041","article-title":"The Frontier of Precision Medicine: Application of Single-Cell Multi-Omics in Preimplantation Genetic Diagnosis","volume":"23","author":"Zhang","year":"2024","journal-title":"Brief. Funct. Genom."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Diao, X., Huang, J., Xiang, R., Zhuang, S., Liang, Q., Liang, X., and Zeng, H. (2025). Single-Cell Dual-Omics Reveals Translational and Transcriptional Landscapes and Regulations in Oocytes from Ovarian Endometriosis Patients. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1534648"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"Genome Editing. The New Frontier of Genome Engineering with CRISPR-Cas9","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.addr.2021.03.010","article-title":"Organ-on-a-Chip Technology for the Study of the Female Reproductive System","volume":"173","author":"Young","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14584","DOI":"10.1038\/ncomms14584","article-title":"A Microfluidic Culture Model of the Human Reproductive Tract and 28-Day Menstrual Cycle","volume":"8","author":"Xiao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"10439","DOI":"10.1038\/s41467-025-65406-7","article-title":"Microengineered Patient-Derived Endometrium-on-a-Chip for the Evaluation of Endometrial Receptivity and Personalised Translational Medicine","volume":"16","author":"Lee","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_91","first-page":"551","article-title":"Microfluidic Chip-Integrated Vascularized Endometrial Complexes: Mitochondrial Function and Paracrine Crosstalk Enhance Regenerative Potential","volume":"54","author":"Dai","year":"2025","journal-title":"Bioact. Mater."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"100276","DOI":"10.1016\/j.medntd.2023.100276","article-title":"Organoid Intelligence: Integration of Organoid Technology and Artificial Intelligence in the New Era of in Vitro Models","volume":"21","author":"Shi","year":"2024","journal-title":"Med. Nov. Technol. Devices"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"102135","DOI":"10.1016\/j.gde.2023.102135","article-title":"Human Blastoid as an in Vitro Model of Human Blastocysts","volume":"84","author":"Liu","year":"2024","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1016\/j.cell.2023.07.028","article-title":"An Ethical Framework for Human Embryology with Embryo Models","volume":"186","author":"Rivron","year":"2023","journal-title":"Cell"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1080\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:29:41Z","timestamp":1788866981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":94,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091080"],"URL":"https:\/\/doi.org\/10.3390\/genes17091080","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}