Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice.

Abstract

The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development. Therefore, the aim of this study was to identify miRNA profiles in serum exosomes of mice induced to estropause and treated with 17β-estradiol (E2). Female mice were divided into three groups including control (CTL), injected with 4-Vinylcyclohexene diepoxide (VCD), and injected with VCD plus E2 (VCD + E₂). Estropause was confirmed by acyclicity and a significant reduction in the number of ovarian follicles (p < 0.05). Body mass gain during estropause was higher in VCD and VCD + E2 compared to CTL females (p = 0.02). Sequencing of miRNAs was performed from exosomes extracted from serum, and 402 miRNAs were detected. Eight miRNAs were differentially regulated between CTL and VCD groups, seven miRNAs regulated between CTL and VCD + E2 groups, and ten miRNAs regulated between VCD and VCD + E2 groups. Only miR-200a-3p and miR-200b-3p were up-regulated in both serum exosomes and ovarian tissue in both VCD groups, suggesting that these exosomal miRNAs could be associated with ovarian activity. In the hepatic tissue, only miR-370-3p (p = 0.02) was up-regulated in the VCD + E2 group, as observed in serum. Our results suggest that VCD-induced estropause and E2 replacement have an impact on the profile of serum exosomal miRNAs. The miR-200 family was increased in serum exosomes and ovarian tissue and may be a candidate biomarker of ovarian function.