Mouse Bone Mesenchymal Stem Cells Attenuate Apoptosis by Regulating the Bcl2/Caspase3 Signaling Pathway in Premature Ovarian Failure.

Abstract

Premature ovarian failure (POF) refers to ovarian failure and its occurrence and development are closely related to the apoptosis signaling pathway. However, the mechanism of bone mesenchymal stem cells (BMSCs) affect the regulation of apoptosis in POF has not been fully elucidated. The GSE128240 microarray dataset were downloaded from the Gene Expression Omnibus. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A mouse model of POF induced by cyclophosphamide (CTX) treatment was established. POF model mice were treated with mBMSCs for 4 weeks. Ovarian failure was evaluated by haematoxylin-eosin (HE) staining, the levels of oestradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH), and the number of follicles. Western blotting and immunohistochemical methods were used to measure the levels of Bcl-2, Bax and Caspase-3 proteins in the ovarian tissue of mice. Total of 1816 differentially expressed genes (DEGs) identified. The PI3K-Akt signaling pathway and ovarian steroidogenesis were functionally enriched through GO enrichment and KEGG analyses. Furthermore, the number of follicles and E2 concentration were significantly increased, and the FSH and LH concentrations were significantly decreased in CTX-induced mice treated with mBMSCs. mBMSCs attenuated apoptosis in CTX-induced mouse ovaries. Levels of Bax and Caspase-3 proteins were significantly decreased in the ovarian tissue of CTX-treated mice and significantly increased after mBMSCs treatment. Thus, mBMSCs attenuated apoptosis in CTX-induced mouse ovaries by regulating the Bcl2/Caspase3 signaling pathway, effectively treating POF.