Impaired decidualization and angiogenesis in eutopic endometrium of endometriosis: insights from in vitro models†.

Endometriosis markedly compromises female fertility, and although endometrial dysfunction likely plays a role in this pathology, its precise mechanistic contributions remain poorly understood. This study aims to investigate the decidualization and angiogenic capacity of eutopic endometrial in endometriosis patients. The study enrolled 30 participants, including 15 infertile patients with endometriosis (EMS group) and 15 patients with benign gynecological conditions who underwent laparoscopic treatment (negative control group, NC group). Immunohistochemistry, F-actin staining, qRT-PCR, Western blot, ELISA, and tube formation assays were used to analyze decidual endometrial stromal cell (ESC) morphology, measure protein expression associated with decidualization and angiogenesis. Secretory phase endometrium from endometriosis patients EMS group showed significantly reduced expression of decidual markers (PRL, IGFBP1, HOXA10, BMP2) and angiogenic-related proteins (ANG2, VEGFA, VEGFR1) versus NC group. Primary ESCs isolated from proliferative phase endometrium tissue of endometriosis patients showed impaired decidualization under hormonal induction, with attenuated morphological transformation, downregulated decidual-related proteins (P < 0.05). Angiogenic dysfunction was evidenced by decreased VEGFA secretion (P = 0.026), reduced angiogenic-related proteins (P < 0.05), and impaired HUVEC tube formation in cocultures (P < 0.05). Overall, endometriosis-associated infertility involves intrinsic defects in decidualization and angiogenesis. This may provide new perspectives for improving the reproductive outcomes of patients with endometriosis.