ITGA3 participates in the pathogenesis of recurrent spontaneous abortion by downregulating ULK1-mediated autophagy to inhibiting trophoblast function.

Recurrent spontaneous abortion (RSA) is a significant challenge encountered by couples of reproductive ages, with inadequate trophoblast invasion identified as a primary factor in RSA pathogenesis. However, the precise molecular mechanisms through which trophoblast cell dysfunction leads to RSA remain incompletely understood. Research has highlighted the critical role of integrins in embryo implantation and development. Although integrin α-3 (ITGA3) is recognized for its promotion of invasion in cancer cells, its involvement in miscarriage remains poorly characterized. This investigation initially assessed ITGA3 expression in villous tissues obtained from patients with RSA and patients with induced abortion. The findings demonstrated a notable reduction in ITGA3 levels in the villous tissues of patients with RSA compared with the control group. Subsequent in vitro analyses indicated that ITGA3 knockdown inhibited the migration, invasion, and proliferation of trophoblast cells. Through RNA sequencing and subsequent experimentation, it was revealed that ITGA3 regulated Unc51-like kinase 1 (ULK1)-mediated autophagy to influence trophoblast cell invasion, migration, and proliferation. Furthermore, utilizing a miscarriage animal model, the diminished expression of ITGA3 and ULK1 in the placentas of RSA mice was confirmed. In conclusion, the study findings suggest that the downregulation of ITGA3 suppresses ULK1 expression, consequently impeding autophagy to initiation and impeding trophoblast cell invasion and migration, thereby contributing to the pathological progression of RSA.NEW & NOTEWORTHY There is a strong correlation between the reduced expression of ITGA3 in villous tissues and RSA. ITGA3 facilitates the expression of ULK1, thereby promoting autophagy formation and elevating autophagy levels in trophoblast cells. Consequently, this enhances the invasion and migration abilities of trophoblast cells.