Defective uterine spiral artery remodelling and placental senescence in a pregnant rat model of polycystic ovary syndrome.

Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodelling. The mechanisms underlying this association are still unclear, as are whether hyperandrogenism and insulin resistance - the two common manifestations of polycystic ovary syndrome (PCOS) - affect uterine SpA remodelling. This study verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher foetal mortality. It also found that exposure to DHT and INS dysregulated the expression of angiogenesis-related genes in the uterus and placenta. It also decreased expression of endothelial nitric oxide synthase and matrix metallopeptidases 2 and 9, increased fibrotic collagen deposits in the uterus, and reduced expression of marker genes for SpA-associated trophoblast giant cells. These changes were related to a greater proportion of un-remodelled uterine SpAs and a smaller proportion of highly remodelled arteries in DHT+INS-exposed rats. Placentas from DHT+INS-exposed rats exhibited decreased basal and labyrinth zone regions, reduced maternal blood spaces, diminished labyrinth vascularity, and an imbalance in the abundance of vascular and smooth muscle proteins. Furthermore, placentas from DHT+INS-exposed rats showed expression of placental insufficiency markers and a significant increase in cell senescence-associated protein levels. Altogether, this work demonstrates increased pregnancy complications in PCOS may be mediated by problems with uterine SpA remodelling, placental functionality, and placental senescence.