PDF(Pubmed)
Abstract：
Androgen excess and metabolic abnormality largely contribute to the pathogenesis of polycystic ovarian syndrome (PCOS), which primarily precipitates ovarian dysfunction and infertility in reproductive-age women. Impaired mitochondrial function and epigenetic alteration have been linked to the development of PCOS. However, it is unknown whether acetate would exert a therapeutic effect on ovarian mitochondrial dysfunction in PCOS. Herein, the study hypothesized that acetate reverses ovarian mitochondrial dysfunction in experimental PCOS rat model, possibly through modulation of mitofusin-2 (MFn2). Eight-week-old female Wistar rats were randomized into four groups (n = 5). Induction of PCOS was performed by 1 mg/kg letrozole (p.o.), administered for 21 days. Thereafter, the rats were treated with acetate (200 mg/kg; p.o.) for 6 weeks. The PCOS rats demonstrated androgen excess, multiple ovarian cysts, elevated anti-mullerian hormone and leptin and decreased SHBG, adiponectin and 17-β estradiol with corresponding increase in ovarian transforming growth factor-β1. Additionally, inflammation (tumor growth factor and nuclear factor-kB), elevated caspase-6, decreased hypoxia-inducible factor-1α and elevated histone deacetylase-2 (HDAC2) were observed in the ovaries of PCOS rats, while mitochondrial abnormality with evidence of decreased adenosine triphosphate synthase and MFn2 was observed in rats with PCOS. Treatment with acetate reversed the alterations. The present results collectively suggest that acetate ameliorates ovarian mitochondrial abnormality, a beneficial effect that is accompanied by MFn2 with consequent normalization of reproductive-endocrine profile and ovarian function. Perhaps, the present data provide hope for PCOS individuals that suffer infertility.
摘要：
雄激素过量和代谢异常在很大程度上促进了多囊卵巢综合征(PCOS)的发病,主要导致育龄妇女卵巢功能障碍和不孕。线粒体功能受损和表观遗传改变与PCOS的发展有关。然而,乙酸盐是否对PCOS患者卵巢线粒体功能障碍有治疗作用尚不清楚.在这里，本研究假设乙酸盐逆转PCOS大鼠模型中的卵巢线粒体功能障碍,可能通过mitofusin-2（MFn2）的调制。将8周龄雌性Wistar大鼠随机分为4组(n=5)。PCOS的诱导是通过1mg/kg来曲唑（p.o.），给药21天。此后,用乙酸盐(200mg/kg;p.o.)处理大鼠6周。PCOS大鼠表现出雄激素过量，多发性卵巢囊肿,抗苗勒管激素和瘦素升高，SHBG降低，脂联素和17-β雌二醇与卵巢转化生长因子-β1相应增加。此外,炎症（肿瘤生长因子和核因子-kB），在PCOS大鼠的卵巢中观察到caspase-6升高，缺氧诱导因子-1α降低和组蛋白去乙酰化酶-2（HDAC2）升高，在PCOS大鼠中观察到线粒体异常，有三磷酸腺苷合酶和MFn2降低的证据。用乙酸盐处理逆转了这种改变。目前的结果共同表明，乙酸盐改善卵巢线粒体异常，伴随着MFn2的有益作用，随之而来的生殖内分泌特征和卵巢功能的正常化。也许,目前的数据为患有不孕症的PCOS患者提供了希望.
