Ovarian Microvascular Endothelial Cell Migration Is Dysregulated in PMOS

The objective of this study is to investigate whether ovarian microvascular endothelial cells (OMECs) from women with polyendocrine metabolic ovarian syndrome (PMOMECs) exhibit altered angiogenic responses compared with cells from healthy oocyte donors (HOMECs). This is a laboratory-based cross-sectional study using HOMECs and PMOMECs obtained from discarded follicular aspirates. Expression of mRNA and protein for VEGF receptors (FLT1, KDR) and PGE2 receptors (PTGER1-4) were assessed using qPCR and immunofluorescence. OMECs were treated in vitro with VEGFA, PGE2, or receptor-selective agonists. Migration was quantified via porous membrane inserts and live cell tracking. Proliferation was measured via BrdU incorporation. FLT1 and KDR mRNA and protein levels were similar between HOMECs and PMOMECs. PTGER2 mRNA was higher and PTGER3 mRNA was lower in PMOMECs. VEGFA and PGE2 significantly stimulated migration and proliferation in HOMECs. In contrast, PMOMECs failed to exhibit increased migration in response to PGE2 or selective PTGER agonists, while VEGFA-induced migration remained comparable to migration of HOMECs. Live cell tracking revealed that PMOMEC migration resulted in decreased overall net distance traveled and reduced directional persistence (less linear movement) compared with HOMECs. These findings demonstrate that ovarian microvascular endothelial cells from women with PMOS display impaired angiogenic responses to PGE2, which may contribute to altered follicle growth and anovulation in PMOS.