{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:53:45Z","timestamp":1790142825545,"version":"4.0.1"},"reference-count":147,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    During male fetal development, testosterone plays an essential role in the differentiation and maturation of the male reproductive system. Deficient fetal testosterone production can result in variations of sex differentiation that may cause infertility and even increased tumor incidence later in life. Fetal Leydig cells in the fetal testis are the major androgen source in mammals. Although fetal and adult Leydig cells are similar in their functions, they are two distinct cell types, and therefore, the knowledge of adult Leydig cells cannot be directly applied to understanding fetal Leydig cells. This review summarizes our current knowledge of fetal Leydig cells regarding their cell biology, developmental biology, and androgen production regulation in rodents and human. Fetal Leydig cells are present in basement membrane\u2010enclosed clusters in between testis cords. They originate from the mesonephros mesenchyme and the coelomic epithelium and start to differentiate upon receiving a Desert Hedgehog\u00a0signal from Sertoli cells or being released from a NOTCH signal from endothelial cells. Mature fetal Leydig cells produce androgens. Human fetal Leydig cell steroidogenesis is LHCGR (Luteinizing Hormone Chronic Gonadotropin Receptor) dependent, while rodents are not, although other G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    \u2010protein coupled receptors might be involved in rodent steroidogenesis regulation. Fetal steroidogenesis ceases after sex differentiation is completed, and some fetal Leydig cells dedifferentiate to serve as stem cells for adult testicular cell types. Significant gaps are acknowledged: (1) Why are adult and fetal Leydig cells different? (2) What are\n                    <jats:italic>bona fide<\/jats:italic>\n                    progenitor and fetal Leydig cell markers? (3) Which signaling pathways and transcription factors regulate fetal Leydig cell steroidogenesis? It is critical to discover answers to these questions so that we can understand vulnerable targets in fetal Leydig cells and the mechanisms for androgen production that when disrupted, leads to variations in sex differentiation that range from subtle to complete sex reversal.\n                  <\/jats:p>","DOI":"10.1002\/mrd.23739","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:55:25Z","timestamp":1710377725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Fetal Leydig cells: What we know and what we don't"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-3796","authenticated-orcid":false,"given":"Keer","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine University of Wisconsin\u2010Madison Madison Wisconsin USA"},{"name":"Cellular and Molecular Biology Graduate Program University of Wisconsin\u2010Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5787-8856","authenticated-orcid":false,"given":"Joan S.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine University of Wisconsin\u2010Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/9629"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110935"},{"key":"e_1_2_7_4_1","first-page":"129","article-title":"Ontogeny of mouse Sertoli, Leydig and peritubular myoid cells from embryonic day 10 to adulthood","volume":"129","author":"Aksel S.","year":"2022","journal-title":"Differentiation"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0438"},{"key":"e_1_2_7_6_1","first-page":"1039","article-title":"Recherches sur la signification physiologique de la glande interstitielle du testicule des mammif\u00e8res. 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