Reproduction and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, U.P., India.
Toxicol Appl Pharmacol. 2022 Sep 15;451:116173. doi: 10.1016/j.taap.2022.116173. Epub 2022 Jul 22.
The association between inflammation and metabolic disturbances leads to various female pathophysiological conditions. Bacterial lipopolysaccharide (LPS), found in the outer membrane of gram-negative bacteria, elicits an oxidative and inflammatory response that profoundly interferes with female reproductive health. We investigated the ameliorative action of melatonin on LPS-induced ovarian pathophysiology in golden hamsters, Mesocricetus auratus. Hamsters were administered with exogenous melatonin (5 mg/kg BW) and LPS (100 μg/kg BW) intraperitoneally for 7 days. LPS treatment impaired ovarian folliculogenesis as evident by histoarchitecture (elevated number of atretic follicles, reduced number of growing follicles and corpus luteum) and steroidogenesis (decreased aromatase/ERα, estradiol and progesterone). On the other hand, LPS administration also perturbed thyroid hormone (T3 and T4) homeostasis, ovarian melatonin receptor (MT-1) expression, antioxidant potential (SOD and catalase) and concomitantly elevated nitro-oxidative stress (decreased SOD, catalase and elevated CRP, TNFα and nitrate/nitrite level) and inflammatory load (NFĸB and COX-2) which culminated into ovarian follicular apoptosis (elevated caspase-3). LPS also disrupted metabolic homeostasis as indicated by hyperinsulinemia with a simultaneous decrease in ovarian IR/GLUT-4 and glucose content. Moreover, LPS treatment decreased expressions of key markers of ovarian physiology (SIRT-1, pErk1/2, PI3K and pAkt). Melatonin co-treatment with LPS improve these detrimental changes proposing melatonin as a potent therapeutic candidate against ovarian dysfunction induced by endotoxin.
炎症与代谢紊乱之间的关联导致了各种女性生理病理状况。细菌脂多糖（LPS）存在于革兰氏阴性菌的外膜中，可引发氧化和炎症反应，严重干扰女性生殖健康。我们研究了褪黑素对内毒素诱导的金黄仓鼠（Mesocricetus auratus）卵巢病理生理学的改善作用。仓鼠经腹腔给予外源性褪黑素（5mg/kgBW）和 LPS（100μg/kgBW），共 7 天。LPS 处理破坏了卵巢卵泡发生，表现为组织学结构（闭锁卵泡数量增加，生长卵泡和黄体数量减少）和甾体生成（芳香化酶/ERα、雌二醇和孕酮减少）。另一方面，LPS 给药还扰乱了甲状腺激素（T3 和 T4）稳态、卵巢褪黑素受体（MT-1）表达、抗氧化潜力（SOD 和过氧化氢酶），并同时升高了硝基氧化应激（SOD、过氧化氢酶减少，CRP、TNFα 和硝酸盐/亚硝酸盐水平升高）和炎症负荷（NFκB 和 COX-2），导致卵巢卵泡细胞凋亡（caspase-3 升高）。LPS 还破坏了代谢稳态，表现为高胰岛素血症，同时伴有卵巢 IR/GLUT-4 和葡萄糖含量减少。此外，LPS 处理降低了卵巢生理学关键标志物的表达（SIRT-1、pErk1/2、PI3K 和 pAkt）。褪黑素与 LPS 共同处理可改善这些不利变化，表明褪黑素是对抗内毒素诱导的卵巢功能障碍的有效治疗候选物。
