Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong Province, China.
Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
Cell Rep Med. 2024 Aug 20;5(8):101678. doi: 10.1016/j.xcrm.2024.101678. Epub 2024 Aug 2.
Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, β-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or β-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, β-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that β-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.
化疗诱导的卵巢早衰（CIPOI）在接受癌症治疗的女性中引发性腺毒性，导致卵巢储备减少和生育能力下降，但目前尚无有效的治疗方法。在我们的研究中，顺铂诱导的 POI 小鼠模型中的粪便微生物群移植表明，肠道微生物组的失调会对 CIPOI 中的卵巢健康产生负面影响。多组学分析显示，与健康对照组相比，CIPOI 组中的雷氏乳杆菌及其代谢产物β-Resorcylic 酸显著减少。补充雷氏乳杆菌或β-RA 可减轻顺铂引起的激素紊乱、形态损伤和卵泡储备减少。最重要的是，β-RA 预处理可有效保护卵母细胞功能、胚胎发育和胎儿健康，从而防止化疗引起的生育能力下降。我们的研究结果表明，β-RA 抑制性别决定区 Y 框 7 的核积累，从而减少 Bcl-2 相关 X 激活并抑制颗粒细胞凋亡。这些发现强调了针对肠道-卵巢轴进行生育力保存的治疗潜力，可用于 CIPOI。
