Hydrogen sulfide inhibits the rupture of fetal membranes throngh anti-aging pathways.

INTRODUCTION: To investigate the relationship between hydrogen sulfide(H2S) and the senescence level of the fetal membranes, and to elucidate how H2S affects the integrity of the fetal membranes. METHODS: The H2S and the senescence levels of fetal membranes, and the expressions of H2S synthase CBS and CSE were detected in the preterm (PT) group and the preterm premature ruptured membranes (pPROM) group. The effects of H2S donors and knockdown of CBS on the senescence level of amniotic epithelial cells, and the expression level of matrix metalloproteinases (MMPs) and epithelial-mesenchymal translation (EMT) were observed. RESULTS: The level of H2S in the fetal membranes in the pPROM group is significantly lower than that in the PT group matched for gestational age. The level of H2S is negatively correlated with the senescence level of fetal membranes. Treatment with H2S donors reduced cell senescence and MMPs expression, but did not affect EMT. CBS siRNA transfection accelerated the senescence of amniotic epithelial cells, and promoted the expression of MMPs and EMT occurrence, but l-cysteine could reverse these effects. DISCUSSION: Our study suggests that H2S, through its anti-aging effect, can influence the expression of MMPs and EMT, thereby contributing to the maintenance of fetal membrane integrity.

miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia.

PURPOSE: Dysregulated behaviors of trophoblast cells leading to defective placentation are considered the main cause of preeclampsia (PE). Abnormal miRNA expression profiles have been observed in PE placental tissue, indicating the significant role of miRNAs in PE development. This study aimed to investigate the expression of miR-101-5p in PE placental tissue and its biological functions. METHODS: The expression of miR-101-5p in placental tissue was detected by quantitative real-time PCR (qRT-PCR). The localization of miR-101-5p in term placental tissue and decidual tissue was determined by the fluorescence in situ hybridization (FISH)-immunofluorescence (IF) double labeling assay. The effect of miR-101-5p on the migration, invasion, proliferation, and apoptosis of the HTR8/SVneo trophoblast cells was investigated. Online databases combined with transcriptomics were used to identify potential target genes and related pathways of miR-101-5p. Finally, the interaction between miR-101-5p and the target gene was verified by qRT-PCT, WB, dual-luciferase reporter assay, and rescue experiments. RESULTS: The study found that miR-101-5p was upregulated in PE placental tissue compared to normal controls and was mainly located in various trophoblast cell subtypes in placental and decidual tissues. Overexpression of miR-101-5p impaired the migration and invasion of HTR8/SVneo cells. DUSP6 was identified as a potential downstream target of miR-101-5p. The expression of miR-101-5p was negatively correlated with DUSP6 expression in HTR8/SVneo cells, and miR-101-5p directly bound to the 3' UTR region of DUSP6. DUSP6 upregulation rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence of miR-101-5p overexpression. Additionally, miR-101-5p downregulated DUSP6, resulting in enhanced ERK1/2 phosphorylation. CONCLUSION: This study revealed that miR-101-5p inhibits the migration and invasion of HTR8/SVneo cells by regulating the DUSP6-ERK1/2 axis, providing a new molecular mechanism for the pathogenesis of PE.