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The aim of this review is to address how DoHAD plays an important role in the phenotypic expression of polycystic ovary syndrome (PCOS), the most common endocrinopathy of women characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. Clinical studies of PCOS women are integrated with findings from relevant animal models to show how intergenerational transmission of these central components of PCOS are programmed through an altered maternal endocrine\u2013metabolic environment that adversely affects the female fetus and long-term offspring health. Prenatal testosterone treatment in monkeys and sheep have been particularly crucial in our understanding of developmental programming of PCOS because organ system differentiation in these species, as in humans, occurs during fetal life. These animal models, along with altricial rodents, produce permanent PCOS-like phenotypes variably characterized by LH hypersecretion from reduced steroid-negative feedback, hyperandrogenism, ovulatory dysfunction, increased adiposity, impaired glucose-insulin homeostasis and other metabolic abnormalities. The review concludes that DoHAD underlies the phenotypic expression of PCOS through an altered maternal endocrine\u2013metabolic environment that can induce epigenetic modifications of fetal genetic susceptibility to PCOS after birth. It calls for improved maternal endocrine\u2013metabolic health of PCOS women to lower their risks of pregnancy-related complications and to potentially reduce intergenerational susceptibility to PCOS and its metabolic derangements in offspring.<\/jats:p>","DOI":"10.1530\/rep-19-0197","type":"journal-article","created":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T08:39:15Z","timestamp":1564735155000},"page":"R1-R13","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":88,"title":["Mechanisms of intergenerational transmission of polycystic ovary syndrome"],"prefix":"10.1093","volume":"159","author":[{"given":"Daniel A","family":"Dumesic","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology , David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis R","family":"Hoyos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology , David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio D","family":"Chazenbalk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology , David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajanigandha","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology , David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasantha","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center , University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2026010712211095100_bib5","article-title":"The prenatally androgenized female rhesus monkey as a model for PCOS","author":"Abbott","year":"1997","journal-title":"Androgen Excess Disorders in Women"},{"key":"2026010712211095100_bib7","doi-asserted-by":"crossref","DOI":"10.1201\/9780203910948.ch10","article-title":"Prenatal androgen excess programs for polycystic ovarian syndrome in female rhesus monkeys","author":"Abbott","year":"2002","journal-title":"Polycystic Ovary Syndrome"},{"key":"2026010712211095100_bib1","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1093\/humupd\/dmi013","article-title":"Androgen excess fetal programming of 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