Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan.
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Chronobiol Int. 2023 Aug;40(8):1004-1027. doi: 10.1080/07420528.2023.2241902. Epub 2023 Aug 7.
Environmental 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.
环境因素，如睡眠限制，通过引起高胰岛素血症、高雄激素血症、胰岛素抵抗和寡排卵或无排卵，导致多囊卵巢综合征（PCOS）。本研究旨在评估昼夜节律紊乱对生殖和代谢功能的影响，并研究 MitoQ10 和热水浴治疗（HTT）的潜在治疗益处。将 60 只雌性大鼠分为 6 组：对照组、MitoQ10 组、HTT 组和 3 组由持续光照（L/L）诱导的 PCOS 组。通过血清生化测量、卵巢大小的超声评估和 14 周时的阴道涂片检查，确认 L/L 诱导的 PCOS 的生殖、内分泌和结构表现。随后，将大鼠分为 L/L（未治疗）、L/L+MitoQ10 治疗和 L/L+HTT 治疗组。在第 22 周末，所有大鼠均被处死。MitoQ10 或 HTT 的治疗部分逆转了 PCOS 的生殖、内分泌和结构特征，导致孤立子宫收缩的振幅降低、卵巢囊性变化和大小以及子宫内膜厚度降低。此外，两种干预措施均改善了升高的血清抗苗勒管激素（AMH）、 kisspeptin、纤维连接蛋白-1、解整合素和金属蛋白酶 19（ADAMTS-19）、脂质谱、稳态模型评估的胰岛素抵抗（HOMA-IR）、氧化应激标志物、卵巢组织中的雄激素受体（AR）及其转录靶基因 FKBP52 免疫染色和子宫雌激素受体α（ER-α）和 PR 免疫染色。总之，MitoQ10 补充和 HTT 显示出改善与昼夜节律紊乱诱导的 PCOS 相关的代谢、生殖和结构紊乱的潜力。这些发现表明这些干预措施在治疗女性 PCOS 方面具有潜在的治疗作用。
