Oxidative stress-induced decreased expression of FABP5 leads to mitochondrial damage and survival disorder of decidual stromal cells in women with recurrent spontaneous abortion.

BACKGROUND

The survival of decidual stromal cells (DSCs) at the maternal-fetal interface is critical for maintaining pregnancy. Dysfunction of DSCs is a significant contributor to recurrent spontaneous abortion (RSA), though the precise regulatory mechanisms remain elusive. Here, we report a marked downregulation of fatty acid-binding protein 5 (FABP5) in decidual tissues and DSCs from RSA donors, suggesting its potential role in RSA pathogenesis.

METHODS

Using decidual tissues and DSCs from normal pregnancy (NP) and RSA donors, we quantified FABP5 expression via qPCR, Western blot, immunofluorescence, and immunohistochemistry. Cellular viability and apoptosis were assessed through CCK8 assays, Ki67 staining, flow cytometry, and TUNEL assays. Mitochondrial integrity and function were evaluated by JC-1 staining, COXIV immunostaining, and ATP quantification. RNA sequencing (RNA-seq) identified downstream targets of FABP5. The migratory and invasive capacities of human extravillous trophoblast cells line (HTR-8/SVneo) were examined via wound healing and transwell assays.

RESULTS

FABP5 expression was significantly reduced in decidual tissues and DSCs from RSA donors, as well as in tert-butyl hydroperoxide (TBHP)-induced oxidative stress models in vitro. siRNA-mediated FABP5 knockdown triggered mitochondrial dysfunction and apoptosis in DSCs, mechanistically linked to mitochondrial ribosomal protein L17 (MRPL17), a pivotal regulator of oxidative respiratory chain enzyme complex synthesis. MRPL17 overexpression alleviated these effects. Furthermore, FABP5 deficiency suppressed CXCL11 secretion, leading to diminished CXCR3 levels in HTR-8/SVneo cells and impairing their migration and invasion.

CONCLUSIONS

Our findings demonstrate that FABP5 downregulation compromises DSC survival by disrupting MRPL17-dependent mitochondrial function, thereby attenuating CXCL11/CXCR3 mediated trophoblast invasion and migration. This study unveils a novel FABP5/MRPL17/CXCL11/CXCR3 axis in RSA pathogenesis, highlighting FABP5 as a potential therapeutic target for pregnancy maintenance.