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In ovariectomized mice, PNA impaired uterine closure during the implantation window, disrupted decidualization, and altered extracellular matrix\u2013 and inflammation-related gene expression. The effects were aggravated by the HF diet. In naturally mated, ovary-intact mice, PNA and HF diet affected decidual and placental gene expression, suggestive of placental dysfunction and inflammation, and induced fetal growth restriction. This study underlines the role of the uterus in adverse pregnancy outcomes in PCOS and identifies possible underlying mechanisms for future studies. Prepregnancy interventions targeting metabolic health and hyperandrogenism should be the next steps to optimize PCOS pregnancy outcomes.<\/jats:p>","DOI":"10.1126\/sciadv.adu3699","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T13:58:21Z","timestamp":1746799101000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Prenatally androgenized PCOS mice have ovary-independent uterine dysfunction and placental inflammation aggravated by high-fat diet"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5545-098X","authenticated-orcid":true,"given":"Lena","family":"Luyckx","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland."},{"name":"Research Group for Implantation, Placentation and Pregnancy, Department of Development and 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