{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:15:39Z","timestamp":1792653339258,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21J00381"],"award-info":[{"award-number":["21J00381"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21K15112"],"award-info":[{"award-number":["21K15112"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["2021FY"],"award-info":[{"award-number":["2021FY"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP20dm0207001"],"award-info":[{"award-number":["JP20dm0207001"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Uehara Memorial Foundation","award":["21J00381"],"award-info":[{"award-number":["21J00381"]}]},{"name":"Uehara Memorial Foundation","award":["21K15112"],"award-info":[{"award-number":["21K15112"]}]},{"name":"Uehara Memorial Foundation","award":["2021FY"],"award-info":[{"award-number":["2021FY"]}]},{"name":"Uehara Memorial Foundation","award":["JP20dm0207001"],"award-info":[{"award-number":["JP20dm0207001"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21J00381"],"award-info":[{"award-number":["21J00381"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21K15112"],"award-info":[{"award-number":["21K15112"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["2021FY"],"award-info":[{"award-number":["2021FY"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20dm0207001"],"award-info":[{"award-number":["JP20dm0207001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Recent success in derivation of functional gametes (oocytes and spermatozoa) from pluripotent stem cells (PSCs) of rodents has made it feasible for future application to large animals including endangered species and to ultimately humans. Here, we summarize backgrounds and recent studies on in vitro gametogenesis from rodent PSCs, and similar approaches using PSCs from large animals, including livestock, nonhuman primates (NHPs), and humans. We also describe additional developing approaches for in vitro reconstitution of reproductive organs, such as the ovary (ovarioid), testis (testisoid), and future challenges in the uterus (uteroid) and oviduct (oviductoid), all of which may be derived from PSCs. Once established, these in vitro systems may serve as a robust platform for elucidating the pathology of infertility-related disorders and ectopic pregnancy, principle of reproduction, and artificial biogenesis. Therefore, these possibilities, especially when using human cells, require consideration of ethical issues, and international agreements and guidelines need to be raised before opening \u201cPandora\u2019s Box\u201d.<\/jats:p>","DOI":"10.3390\/biology11070987","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T20:47:56Z","timestamp":1656535676000},"page":"987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A New Horizon in Reproductive Research with Pluripotent Stem Cells: Successful In Vitro Gametogenesis in Rodents, Its Application to Large Animals, and Future In Vitro Reconstitution of Reproductive Organs Such as \u201cUteroid\u201d and \u201cOviductoid\u201d"],"prefix":"10.3390","volume":"11","author":[{"given":"Sho","family":"Yoshimatsu","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Research Fellow of Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Tokyo 102-0083, Japan"},{"name":"Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Wako-City 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1143-9855","authenticated-orcid":false,"given":"Iori","family":"Kisu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Noce","sequence":"additional","affiliation":[{"name":"Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Wako-City 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/35102186","article-title":"Reprogramming of genome function through epigenetic inheritance","volume":"414","author":"Surani","year":"2001","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrg.2016.88","article-title":"Specification and epigenetic programming of the human germ line","volume":"17","author":"Tang","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1098\/rstb.2003.1324","article-title":"Specification of germ cell fate in mice","volume":"358","author":"Saitou","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.devcel.2016.09.007","article-title":"The Germ Cell Fate of Cynomolgus Monkeys Is Specified in the Nascent Amnion","volume":"39","author":"Sasaki","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108735","DOI":"10.1016\/j.celrep.2021.108735","article-title":"Specification and epigenomic resetting of the pig germline exhibit conservation with the human lineage","volume":"34","author":"Zhu","year":"2021","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109812","DOI":"10.1016\/j.celrep.2021.109812","article-title":"Tracing the emergence of primordial germ cells from bilaminar disc rabbit embryos and pluripotent stem cells","volume":"37","author":"Kobayashi","year":"2021","journal-title":"Cell Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1247\/csf.26.131","article-title":"Vasa homolog genes in mammalian germ cell development","volume":"26","author":"Noce","year":"2001","journal-title":"Cell Struct. Funct."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/dgd.12653","article-title":"Environmental factors for establishment of the dormant state in oocytes","volume":"62","author":"Hayashi","year":"2020","journal-title":"Dev. Growth Differ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/309255a0","article-title":"Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines","volume":"309","author":"Bradley","year":"1984","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15022","DOI":"10.1073\/pnas.1009424107","article-title":"Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases","volume":"107","author":"Meyer","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2013.04.025","article-title":"One-step generation of mice carrying mutations in multiple genes by CRISPR\/Cas-mediated genome engineering","volume":"153","author":"Wang","year":"2013","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14223","DOI":"10.1073\/pnas.1009582107","article-title":"Generation of genetically modified rats from embryonic stem cells","volume":"107","author":"Kawamata","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2011.12.007","article-title":"Generation of chimeric rhesus monkeys","volume":"148","author":"Tachibana","year":"2012","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cell.2011.12.016","article-title":"Chimeric primates: Embryonic stem cells need not apply","volume":"148","author":"Trounson","year":"2012","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.neuron.2015.03.021","article-title":"Brains, genes, and primates","volume":"86","author":"Callaway","year":"2015","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.stem.2009.05.015","article-title":"Naive and primed pluripotent states","volume":"4","author":"Nichols","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1126\/science.1083452","article-title":"Derivation of oocytes from mouse embryonic stem cells","volume":"300","author":"Hubner","year":"2003","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11457","DOI":"10.1073\/pnas.1932826100","article-title":"Embryonic stem cells can form germ cells in vitro","volume":"100","author":"Toyooka","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature03813","article-title":"Blimp1 is a critical determinant of the germ cell lineage in mice","volume":"436","author":"Ohinata","year":"2005","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cell.2009.03.014","article-title":"A signaling principle for the specification of the germ cell lineage in mice","volume":"137","author":"Ohinata","year":"2009","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.devcel.2013.11.001","article-title":"A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants","volume":"27","author":"Aramaki","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"dev174938","DOI":"10.1242\/dev.174938","article-title":"Developmental analyses of mouse embryos and adults using a non-overlapping tracing system for all three germ layers","volume":"146","author":"Serizawa","year":"2019","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature12417","article-title":"Induction of mouse germ-cell fate by transcription factors in vitro","volume":"501","author":"Nakaki","year":"2013","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cell.2011.06.052","article-title":"Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells","volume":"146","author":"Hayashi","year":"2011","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1126\/science.1226889","article-title":"Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice","volume":"338","author":"Hayashi","year":"2012","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/nprot.2013.090","article-title":"Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells","volume":"8","author":"Hayashi","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nature20104","article-title":"Reconstitution in vitro of the entire cycle of the mouse female germ line","volume":"539","author":"Hikabe","year":"2016","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.celrep.2016.11.026","article-title":"In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells","volume":"17","author":"Ishikura","year":"2016","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature09850","article-title":"In vitro production of functional sperm in cultured neonatal mouse testes","volume":"471","author":"Sato","year":"2011","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/j.stem.2021.08.005","article-title":"In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells","volume":"28","author":"Ishikura","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_31","unstructured":"Arey, L.B. (1965). Developmental Anatomy: A Textbook and Laboratory Manual of Embryology, Saunders. [7th ed.]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12561","DOI":"10.1038\/ncomms12561","article-title":"Hedgehog-BMP signalling establishes dorsoventral patterning in lateral plate mesoderm to trigger gonadogenesis in chicken embryos","volume":"7","author":"Yoshino","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.semcdb.2018.09.002","article-title":"Epithelial-to-mesenchymal transition-based morphogenesis of dorsal mesentery and gonad","volume":"92","author":"Yoshino","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabe0237","DOI":"10.1126\/science.abe0237","article-title":"Generation of ovarian follicles from mouse pluripotent stem cells","volume":"373","author":"Yoshino","year":"2021","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1126\/science.abl4412","article-title":"Functional primordial germ cell-like cells from pluripotent stem cells in rats","volume":"376","author":"Oikawa","year":"2022","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1095\/biolreprod.114.121640","article-title":"Generation of mouse functional oocytes in rat by xeno-ectopic transplantation of primordial germ cells","volume":"91","author":"Hayama","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1038\/s41467-018-07740-7","article-title":"Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche","volume":"9","author":"Sosa","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.stem.2015.06.014","article-title":"Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells","volume":"17","author":"Sasaki","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/biolre\/ioz205","article-title":"Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeysdagger","volume":"102","author":"Sakai","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.stemcr.2021.03.002","article-title":"Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species","volume":"16","author":"Yoshimatsu","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41556-019-0333-2","article-title":"Establishment of porcine and human expanded potential stem cells","volume":"21","author":"Gao","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cell.2014.12.013","article-title":"SOX17 is a critical specifier of human primordial germ cell fate","volume":"160","author":"Irie","year":"2015","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1126\/science.aat1674","article-title":"Generation of human oogonia from induced pluripotent stem cells in vitro","volume":"362","author":"Yamashiro","year":"2018","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/s41596-020-0297-5","article-title":"Generation of human oogonia from induced pluripotent stem cells in culture","volume":"15","author":"Yamashiro","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1038\/s41467-020-19350-3","article-title":"Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells","volume":"11","author":"Hwang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.stem.2017.09.005","article-title":"Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells","volume":"21","author":"Kojima","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/s41467-020-15042-0","article-title":"A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons","volume":"11","author":"Sybirna","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1095\/biolreprod.107.066175","article-title":"The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture","volume":"78","author":"Perrett","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109075","DOI":"10.1016\/j.celrep.2021.109075","article-title":"The embryonic ontogeny of the gonadal somatic cells in mice and monkeys","volume":"35","author":"Sasaki","year":"2021","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.devcel.2020.05.010","article-title":"Single-Cell RNA Sequencing of Human, Macaque, and Mouse Testes Uncovers Conserved and Divergent Features of Mammalian Spermatogenesis","volume":"54","author":"Shami","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1530\/REP-09-0158","article-title":"Comparative aspects of implantation","volume":"138","author":"Bazer","year":"2009","journal-title":"Reproduction"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41586-021-03416-3","article-title":"Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis","volume":"593","author":"Oldak","year":"2021","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-cell reconstruction of the early maternal-fetal interface in humans","volume":"563","author":"Efremova","year":"2018","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1038\/nprot.2014.186","article-title":"In vitro culture of mouse blastocysts beyond the implantation stages","volume":"9","author":"Bedzhov","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.cell.2014.01.023","article-title":"Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation","volume":"156","author":"Bedzhov","year":"2014","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.devcel.2021.12.023","article-title":"An ex vivo system to study cellular dynamics underlying mouse peri-implantation development","volume":"57","author":"Ichikawa","year":"2022","journal-title":"Dev. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"eaax7890","DOI":"10.1126\/science.aax7890","article-title":"In vitro culture of cynomolgus monkey embryos beyond early gastrulation","volume":"366","author":"Ma","year":"2019","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eaaw5754","DOI":"10.1126\/science.aaw5754","article-title":"Dissecting primate early post-implantation development using long-term in vitro embryo culture","volume":"366","author":"Niu","year":"2019","journal-title":"Science"},{"key":"ref_59","first-page":"dev.99743","article-title":"In vitro culture of ovine embryos up to early gastrulating stages","volume":"149","author":"Used","year":"2022","journal-title":"Development"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1038\/s41588-021-00972-2","article-title":"Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro","volume":"53","author":"Handfield","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"605301","DOI":"10.3389\/fcell.2021.605301","article-title":"Mechanistic Drivers of Mullerian Duct Development and Differentiation into the Oviduct","volume":"9","author":"Rota","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ydbio.2006.09.046","article-title":"The origin of the Mullerian duct in chick and mouse","volume":"302","author":"Guioli","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/ar.a.10061","article-title":"Development of the human Mullerian duct in the sexually undifferentiated stage","volume":"272","author":"Hashimoto","year":"2003","journal-title":"Anat. Rec. A Discov. Mol. Cell. Evol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.reprotox.2019.03.006","article-title":"Retinoic acid signaling determines the fate of the uterus from the mouse Mullerian duct","volume":"86","author":"Nakajima","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14354","DOI":"10.1073\/pnas.1608808113","article-title":"Retinoic acid signaling determines the fate of uterine stroma in the mouse Mullerian duct","volume":"113","author":"Nakajima","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"a023002","DOI":"10.1101\/cshperspect.a023002","article-title":"The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility","volume":"6","author":"Du","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.stem.2019.11.012","article-title":"Endometrial Axin2(+) Cells Drive Epithelial Homeostasis, Regeneration, and Cancer following Oncogenic Transformation","volume":"26","author":"Syed","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"23132","DOI":"10.1073\/pnas.1915389116","article-title":"Self-renewing endometrial epithelial organoids of the human uterus","volume":"116","author":"Fitzgerald","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e69603","DOI":"10.7554\/eLife.69603","article-title":"Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids","volume":"10","author":"Rawlings","year":"2021","journal-title":"eLife"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.stemcr.2018.10.002","article-title":"Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells: Role of the WNT\/CTNNB1 Pathway","volume":"11","author":"Miyazaki","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1089\/ten.tea.2014.0052","article-title":"Regeneration of uterine horns in rats using collagen scaffolds loaded with human embryonic stem cell-derived endometrium-like cells","volume":"21","author":"Song","year":"2015","journal-title":"Tissue Eng. Part A"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41587-020-0547-7","article-title":"A tissue-engineered uterus supports live births in rabbits","volume":"38","author":"Magalhaes","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/humupd\/dmp057","article-title":"Current knowledge of the aetiology of human tubal ectopic pregnancy","volume":"16","author":"Shaw","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1097\/MOT.0000000000000936","article-title":"Uterus transplantation worldwide: Clinical activities and outcomes","volume":"26","author":"Brannstrom","year":"2021","journal-title":"Curr. Opin. Organ Transpl."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1111\/1471-0528.15230","article-title":"Emerging problems in uterus transplantation","volume":"125","author":"Kisu","year":"2018","journal-title":"BJOG"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kisu, I., Banno, K., and Aoki, D. (2022). Considerations in performing hysterectomy secondary to uterus transplantation. Acta Obstet. Gynecol. Scand.","DOI":"10.1111\/aogs.14368"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.stemcr.2021.05.012","article-title":"ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update","volume":"16","author":"Anthony","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s41598-018-37990-w","article-title":"Robust and efficient knock-in in embryonic stem cells and early-stage embryos of the common marmoset using the CRISPR-Cas9 system","volume":"9","author":"Yoshimatsu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41467-019-13897-6","article-title":"A set of monomeric near-infrared fluorescent proteins for multicolor imaging across scales","volume":"11","author":"Matlashov","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/7\/987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:40:25Z","timestamp":1760139625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/7\/987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":81,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["biology11070987"],"URL":"https:\/\/doi.org\/10.3390\/biology11070987","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]}}}