Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China.
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China.
Biochem Pharmacol. 2024 May;223:116193. doi: 10.1016/j.bcp.2024.116193. Epub 2024 Apr 4.
Ovarian aging leads to infertility and birth defects. We aimed to clarify the role of Indole-3-carbinol (I3C) in resistance to oxidative stress, apoptosis, and fibrosis in ovarian aging. I3C was administered via intraperitoneal injection for 3 weeks in young or old mice. Immunohistochemistry; Masson, Sirius red, and TUNEL staining; follicle counting; estrous cycle analysis; and Western blotting were used for validating the protective effect of I3C against ovarian senescence. Human granulosa-like tumor cell line and primary granulosa cells were used for in vitro assay. The results indicated that I3C inhibited ovarian fibrosis and apoptosis while increasing the number of primordial follicles. Mechanistic studies have shown that I3C promoted the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2) and upregulated the expression of heme oxygenase 1 (HO-1). Additionally, I3C increased cell viability and decreased lactate dehydrogenase, malondialdehyde, reactive oxygen species and JC-1 levels. Furthermore, the antioxidant effect of I3C was found to be dependent on the activation of Nrf2 and HO-1, as demonstrated by the disappearance of the effect upon inhibition of Nrf2 expression. In conclusion, I3C can alleviate the ovarian damage caused by aging and may be a protective agent to delay ovarian aging.
卵巢衰老导致不孕和出生缺陷。我们旨在阐明吲哚-3-甲醇 (I3C) 在抵抗氧化应激、细胞凋亡和纤维化方面对卵巢衰老的作用。年轻或年老的小鼠通过腹腔注射 I3C 3 周。免疫组织化学；马松、茜素红和 TUNEL 染色；卵泡计数；动情周期分析；以及 Western blot 用于验证 I3C 对卵巢衰老的保护作用。人颗粒细胞瘤系和原代颗粒细胞用于体外检测。结果表明，I3C 抑制卵巢纤维化和细胞凋亡，同时增加原始卵泡的数量。机制研究表明，I3C 促进核因子红细胞 2 相关因子 (Nrf2) 的核易位，并上调血红素加氧酶 1 (HO-1) 的表达。此外，I3C 增加了细胞活力，降低了乳酸脱氢酶、丙二醛、活性氧和 JC-1 水平。此外，I3C 的抗氧化作用依赖于 Nrf2 和 HO-1 的激活，如抑制 Nrf2 表达后作用消失所证明的那样。总之，I3C 可以减轻衰老引起的卵巢损伤，可能是一种保护剂，可延缓卵巢衰老。
