FGF7 downregulation impairs endometrial receptivity and decidualization via ERK/JNK pathways, contributing to recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) affects 2-5% of women globally, with nearly half of cases remaining unexplained despite various identified etiologies. This significant reproductive challenge highlights a critical gap in understanding the molecular mechanisms governing successful pregnancy. Impaired endometrial receptivity—the uterus's ability to accept an embryo—is a key factor in RSA pathogenesis. Current standard-of-care often lacks targeted interventions for these unexplained cases, underscoring the need for novel therapeutic strategies focusing on fundamental cellular processes like proliferation, apoptosis, and decidualization.

Researchers investigated the role of fibroblast growth factor 7 (FGF7) in recurrent spontaneous abortion (RSA) and impaired endometrial receptivity. They employed bioinformatic analyses alongside experimental approaches using human decidual tissues, as well as cultured human endometrial stromal cells (HESCs) and Ishikawa cells. The study probed the regulatory patterns of FGF7 and its impact on essential cellular processes. Key endpoints included assessing HESC proliferation, apoptosis, and the process of decidualization under conditions of FGF7 suppression (downregulated by approximately 50%). They also explored the involvement of extracellular signal-regulated kinase (ERK) and C-Jun N-Terminal kinase (JNK) pathways.

The study revealed a significant correlation between FGF7 downregulation and disruptions in crucial cellular processes. FGF7 expression was decreased by approximately 50% (p < 0.05) in decidual tissues from RSA patients. This suppression was directly linked to impaired human endometrial stromal cell (HESC) proliferation and altered apoptosis, both pivotal aspects in RSA pathogenesis.

Notably, FGF7 suppression led to significant disruptions in decidualization processes, which are essential for successful embryo implantation and the maintenance of pregnancy. These detrimental effects on endometrial receptivity and decidualization were found to be mediated via the extracellular signal-regulated kinase (ERK) and C-Jun N-Terminal kinase (JNK) pathways. The findings deepen the understanding of the molecular dynamics underlying impaired endometrial receptivity in RSA, highlighting FGF7's critical role.