Oxidized high-density lipoprotein enhances endocrine disorders and ovarian damage in rats.

ABSTRACT: Previous findings have highlighted the association between oxidized high-density lipoprotein (ox-HDL) and polycystic ovary syndrome (PCOS) development; however, the underlying mechanism remains unclear. Under such context, the present study aimed to investigate the mechanism underlying the involvement of ox-HDL in PCOS in relation to the p65/micro-RNA-34a (miR-34a)/FOS axis. PCOS rat models were established with the injection of dehydroepiandrosterone (6 mg/100 g body weight). Both PCOS-modelled rats and granulosa cells (GCs) were received treatment with ox-HDL in order to identify its role in PCOS. Next, apoptosis and viability of GCs were detected with the application of TdT-mediated dUTP Nick-End Labeling and flow cytometry and Cell counting kit-8, respectively. A series of assays were performed to determine the interaction among ox-HDL, p65, miR-34a, FOS and nuclear factor-κB (NF-κB). The results revealed high expression of ox-HDL in PCOS, and enhanced endocrine disorders and ovarian damage in rats. ox-HDL promoted apoptosis of GCs and decreased its viability. ox-HDL activated NF-κB pathway and induced p65 phosphorylation to promote miR-34a expression. miR-34a targeted and inhibited FOS expression. In conclusion, our findings suggested that ox-HDL promoted the activation of p65 and transcription of miR-34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development.

SUBMITTER: Wang L 

PROVIDER: S-EPMC8419193 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature