Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption

ABSTRACTEnvironmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.KEYWORDS: PCOSoxidative stresscircadian rhythmreproductive functionFKBP52Fibulin-1ADAMTS-19 Disclosure statementNo potential conflict of interest was reported by the author(s).Ethical approvalThis study followed the guidelines set by the Institutional Review Board of Hashemite University, which approved (15/2020) the experimental procedures, animal handling, sampling, and euthanasia. Animal handling adhered to the principles outlined in the Guide for Care and Use of Laboratory Animals (NIH publication no. 85–23, revised 2011).Data availability statementThe datasets used in the current study are available from the corresponding author upon reasonable request.Additional informationFundingThe work was supported by the Hashemite University [59/2020].