AI Article Synopsis

  • Recurrent spontaneous abortion (RSA) occurs frequently in couples of reproductive age, with inadequate trophoblast invasion being a key factor in its development.
  • Research indicates that integrins, especially integrin α-3 (ITGA3), play an important role in embryo implantation, but its role in miscarriage has not been well studied.
  • This study found reduced ITGA3 levels in tissues from RSA patients, and through various methods, established that ITGA3 is crucial for trophoblast cell functions by regulating autophagy, ultimately affecting their ability to invade and migrate, contributing to RSA.

Article Abstract

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 cells dysfunction leads to RSA remain incompletely understood. Research has highlighted the critical role of integrins in embryo implantation and development. While 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 RSA patients and induced abortion patients. The findings demonstrated a notable reduction in ITGA3 levels in the villous tissues of RSA patients compared 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 ULK1-mediated autophagy to influence trophoblast cells 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 cells invasion and migration, thereby contributing to the pathological progression of RSA.

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Source
http://dx.doi.org/10.1152/ajpcell.00563.2024DOI Listing

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