ESRRG downregulation in early spontaneous abortion induces mitochondrial damage, leading to impaired trophoblast function

Background: Early spontaneous abortion (ESA) is recognized as the most common complication during pregnancy and is often linked to dysfunction in the trophoblast and placenta. Studies suggest that downregulation of trophoblast oestrogen-related receptor gamma (ESRRG) may play a significant role in the impairment of placental function. In light of these findings, we evaluated the impact of ESRRG on trophoblast and placental function in ESAs, aiming to uncover new targets for diagnosis and treatment.

Patients/Materials and methods: Bioinformatics methods were used to analyse differentially expressed genes in the trophoblast of ESA patients and normal controls. ESA Patients and controls were recruited and the villus tissues were collected. Protein and mRNA levels were determined by western blot and qRT-PCR, respectively. Mitochondrial morphological changes in trophoblasts were observed via transmission electron microscopy. CCK8 and Transwell assays were conducted with ESRRG-knockdown HTR-8/SVneo cells. MitoSOX staining, JC-1 assays and ATP quantification were used to assess mitochondrial function in vitro. In addition, Esrrg was overexpressed in ICR female mice, and the number of embryos in the uterus was determined.

Results: The expression of ESRRG was significantly decreased in the placental villous tissue of ESA patients, accompanied by abnormal mitochondrial morphology and decreased ATP levels in trophoblast cells. Impaired proliferation, invasion, migration and tube formation abilities were observed in ESRRG-downregulated HTR-8/SVneo cells, as well as impaired mitochondrial function. ESRRG overexpression was associated with improved trophoblast functionality in a lipopolysaccharide-induced abortion model in ICR mice, leading to an increased number of retained embryos in the uterus.

Conclusion: In summary, this study revealed that ESRRG downregulation plays an important role in ESA, providing new targets for diagnosis and treatment.

ESRRG; Early spontaneous abortion; mitochondria; trophoblast dysfunction.