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Yet, further studies are required to understand the effects of elevated androgens on cell type\u2010specific placental dysfunction and fetal development. Therefore, a PCOS\u2010like mouse model induced by continuous androgen exposure is examined. The PCOS\u2010mice exhibited impaired placental and embryonic development, resulting in mid\u2010gestation lethality. Co\u2010treatment with the androgen receptor blocker, flutamide, prevents these phenotypes including germ cell specification. Comprehensive profiling of the placenta by whole\u2010genome bisulfite and RNA sequencing shows a reduced proportion of trophoblast precursors, possibly due to the downregulation of\n                    <jats:italic>Cdx2<\/jats:italic>\n                    expression. Reduced expression of\n                    <jats:italic>Gcm1<\/jats:italic>\n                    ,\n                    <jats:italic>Synb<\/jats:italic>\n                    , and\n                    <jats:italic>Prl3b1<\/jats:italic>\n                    is associated with reduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairs placental labyrinth formation. Importantly, human trophoblast organoids exposed to androgens exhibit analogous changes, showing impaired trophoblast differentiation as a key feature in PCOS\u2010related pregnancy complications. These findings provide new insights into the potential cellular targets for future treatments.\n                  <\/jats:p>","DOI":"10.1002\/advs.202309429","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:40:00Z","timestamp":1722300000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-0140","authenticated-orcid":false,"given":"Haojiang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  Stockholm 17177 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