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The PCO morphology results from increased follicular recruitment and persistence of antral follicles, a consequence of reduced follicular growth and atresia, and is driven by cell-specific gene expression changes that are poorly understood. Therefore, using RNA sequencing, cell-specific transcriptional changes were assessed in laser capture microdissection isolated antral follicular granulosa and theca cells from age 21 months control and prenatal T\u2013treated (100 mg intramuscular twice weekly from gestational day 30 to 90; term: 147 days) sheep. In controls, 3494 genes were differentially expressed between cell types with cell signaling, proliferation, extracellular matrix, immune, and tissue development genes enriched in theca; and mitochondrial, chromosomal, RNA, fatty acid, and cell cycle process genes enriched in granulosa cells. Prenatal T treatment 1) increased gene expression of transforming growth factor \u03b2 receptor 1 and exosome component 9, and decreased BCL6 corepressor like 1, BCL9 like, and MAPK interacting serine\/threonine kinase 2 in both cells, 2) induced differential expression of 92 genes that included increased mitochondrial, ribosome biogenesis, ribonucleoprotein, and ubiquitin, and decreased cell development and extracellular matrix-related pathways in granulosa cells, and 3) induced differential expression of 56 genes that included increased noncoding RNA processing, ribosome biogenesis, and mitochondrial matrix, and decreased transcription factor pathways in theca cells. These data indicate that follicular function is affected by genes involved in transforming growth factor signaling, extracellular matrix, mitochondria, epigenetics, and apoptosis both in a common as well as a cell-specific manner and suggest possible mechanistic pathways for prenatal T treatment\u2013induced PCO morphology in sheep.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa094","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T17:48:59Z","timestamp":1591724939000},"source":"Crossref","is-referenced-by-count":10,"title":["Developmental Programming: Sheep Granulosa and Theca Cell\u2013Specific Transcriptional Regulation by Prenatal Testosterone"],"prefix":"10.1210","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-7619","authenticated-orcid":false,"given":"Muraly","family":"Puttabyatappa","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dumesic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M","family":"Bakulski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-7212","authenticated-orcid":false,"given":"Vasantha","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"issue":"5","key":"2021121822272037300_CIT0001","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/er.2015-1018","article-title":"Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome","volume":"36","author":"Dumesic","year":"2015","journal-title":"Endocr Rev."},{"issue":"4","key":"2021121822272037300_CIT0002","doi-asserted-by":"crossref","first-page":"P1","DOI":"10.1530\/EJE-14-0253","article-title":"The polycystic ovary syndrome: a position statement from the European 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