Endometrium dysfunctie bij PCOS: inzichten uit een muismodel, humane endometriale transcriptomics en organoïden

Successful pregnancy depends on the coordinated interaction between the embryo and the endometrium, which undergoes cyclical changes culminating in a short window of implantation. Disruption of this process contributes to implantation failure, abnormal placentation, and pregnancy complications. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, is associated with infertility and adverse pregnancy outcomes. While ovarian and hormonal aspects of PCOS have been extensively studied, endometrial dysfunction has received less attention. Emerging evidence indicates impaired decidualization and disrupted hormone signalling in the PCOS endometrium, yet the molecular mechanisms and the impact of excess body weight remain poorly understood. This study established two new models to investigate PCOS-related endometrial dysfunction, including a prenatally androgenized mouse model exposed to a high-energy diet, and a novel epithelial organoid model. Analyses revealed dysregulated inflammatory and receptivity pathways, with obesity further exacerbating endometrial and placental impairments. These changes reduced fertility in mice and impaired placental development, leading to compromised embryonic growth. Overall, the findings identify specific molecular features of PCOS endometrium, highlight hyperandrogenism and obesity as interacting drivers of reproductive dysfunction, and suggest therapeutic targets to improve fertility and pregnancy outcomes in affected women.