Luyckx Lena, Myllykangas Milena, Saarela Ulla, Virtanen Nikke, Hurskainen Elisa, Savolainen Audrey, Ollikainen Nadja, Norlén Anna-Karin, Ohlsson Claes, Poutanen Matti, Velde Greetje Vande, Arffman Riikka K, Prunskaite-Hyyryläinen Renata, Vriens Joris, Piltonen Terhi T
Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland.
Research Group for Implantation, Placentation and Pregnancy, Department of Development and Regeneration, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium.
Sci Adv. 2025 May 9;11(19):eadu3699. doi: 10.1126/sciadv.adu3699.
Polycystic ovary syndrome (PCOS) is a common hyperandrogenic and metabolic condition in women. The syndrome is linked to subfertility and pregnancy complications, yet the independent effects of exposure to hyperandrogenism and obesity on endometrial function remain unclear. Here, PCOS-like mice were generated using prenatal androgenization (PNA) with dihydrotestosterone, followed by a prepubertal high-fat (HF) or standard diet. In ovariectomized mice, PNA impaired uterine closure during the implantation window, disrupted decidualization, and altered extracellular matrix- 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.
多囊卵巢综合征（PCOS）是一种常见的女性高雄激素血症和代谢性疾病。该综合征与生育力低下和妊娠并发症有关，但高雄激素血症和肥胖对子宫内膜功能的独立影响仍不清楚。在此，通过用二氢睾酮进行产前雄激素化（PNA），然后在青春期前给予高脂（HF）或标准饮食，生成了PCOS样小鼠。在去卵巢小鼠中，PNA损害了着床窗口期的子宫闭合，破坏了蜕膜化，并改变了细胞外基质和炎症相关基因的表达。高脂饮食加剧了这些影响。在自然交配、卵巢完整的小鼠中，PNA和高脂饮食影响了蜕膜和胎盘基因的表达，提示胎盘功能障碍和炎症，并导致胎儿生长受限。这项研究强调了子宫在PCOS不良妊娠结局中的作用，并确定了未来研究可能的潜在机制。针对代谢健康和高雄激素血症的孕前干预措施应是优化PCOS妊娠结局的下一步措施。
