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Expanding on recent reports of prenatal AMH exposure in mice, we have fully characterized the reproductive consequences of prenatal AMH (pAMH) exposure throughout the lifespan of first- and second-generation offspring of both sexes. We also sought to elucidate mechanisms underlying pAMH-induced reproductive effects. There is a known reciprocal relationship between AMH and androgens, and in PCOS and PCOS-like animal models, androgen feedback is dysregulated at the level of the hypothalamus. Kisspeptin neurons express androgen receptors and play a critical role in sexual development and function. We therefore hypothesized that pAMH-induced reproductive phenotypes would be mediated by androgen signaling at the level of kisspeptin cells. We tested the pAMH model in kisspeptin-specific androgen receptor knockout (KARKO) mice and found that virtually all pAMH-induced phenotypes assayed are eliminated in KARKO offspring compared to littermate controls. By demonstrating the necessity of androgen receptor in kisspeptin cells to induce pAMH phenotypes, we have advanced understanding of the interactions between AMH and androgens in the context of prenatal exposure, which could have significant implications for children of women with PCOS.<\/jats:p>","DOI":"10.1210\/endocr\/bqab197","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T18:11:35Z","timestamp":1631815895000},"source":"Crossref","is-referenced-by-count":25,"title":["Reproductive Deficits Induced by Prenatal Antim\u00fcllerian Hormone Exposure Require Androgen Receptor in Kisspeptin Cells"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7765-4200","authenticated-orcid":false,"given":"Emily V","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-2746","authenticated-orcid":false,"given":"Chengxian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-2294","authenticated-orcid":false,"given":"Jessica","family":"Cassin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-3781","authenticated-orcid":false,"given":"Michelle Y","family":"He","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-2305","authenticated-orcid":false,"given":"Ryan D","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-7608","authenticated-orcid":false,"given":"Genevieve E","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-8857","authenticated-orcid":false,"given":"Karen J","family":"Tonsfeldt","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-0410","authenticated-orcid":false,"given":"Pamela L","family":"Mellon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"2021101306534045500_CIT0001","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."},{"issue":"10","key":"2021101306534045500_CIT0002","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1093\/humrep\/17.10.2573","article-title":"Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization","volume":"17","author":"Sir-Petermann","year":"2002","journal-title":"Hum Reprod."},{"issue":"5","key":"2021101306534045500_CIT0003","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3109\/01443615.2010.485254","article-title":"Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels","volume":"30","author":"Barry","year":"2010","journal-title":"J Obstet Gynaecol."},{"issue":"5","key":"2021101306534045500_CIT0004","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1210\/jc.2009-2651","article-title":"Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels","volume":"95","author":"Anderson","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021101306534045500_CIT0005","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ejogrb.2012.10.015","article-title":"Placental steroidogenesis in pregnant women with polycystic ovary syndrome","volume":"166","author":"Maliqueo","year":"2013","journal-title":"Eur J Obstet Gynecol Reprod Biol."},{"issue":"12","key":"2021101306534045500_CIT0006","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1038\/s41591-019-0666-1","article-title":"Prenatal androgen exposure and 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