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Gut microbiota–bile acid‐vitamin D axis plays an important role in determining oocyte quality and embryonic development

卵母细胞 胆酸 生物 胚胎发生 褪黑素 肠道菌群 代谢组学 男科 内分泌学 胆汁酸 胚胎 内科学 细胞生物学 生物化学 生物信息学 医学
作者
Ang Li,Fēi Li,Weihong Song,Zili Lei,Qing‐Yuan Sun,Shao-Yuan Liu,Changyin Zhou,Xue Zhang,Xiaozhen Li,Heide Schatten,Teng Zhang,Qing‐Yuan Sun,Xiang‐Hong Ou
出处
期刊:Clinical and translational medicine [Wiley]
卷期号:13 (10)
标识
DOI:10.1002/ctm2.1236
摘要

To reveal whether gut microbiota and their metabolites are correlated with oocyte quality decline caused by circadian rhythm disruption, and to search possible approaches for improving oocyte quality.A mouse model exposed to continuous light was established. The oocyte quality, embryonic development, microbial metabolites and gut microbiota were analyzed. Intragastric administration of microbial metabolites was conducted to confirm the relationship between gut microbiota and oocyte quality and embryonic development.Firstly, we found that oocyte quality and embryonic development decreased in mice exposed to continuous light. Through metabolomics profiling and 16S rDNA-seq, we found that the intestinal absorption capacity of vitamin D was decreased due to significant decrease of bile acids such as lithocholic acid (LCA), which was significantly associated with increased abundance of Turicibacter. Subsequently, the concentrations of anti-Mullerian hormone (AMH) hormone in blood and melatonin in follicular fluid were reduced, which is the main reason for the decline of oocyte quality and early embryonic development, and this was rescued by injection of vitamin D3 (VD3). Secondly, melatonin rescued oocyte quality and embryonic development by increasing the concentration of lithocholic acid and reducing the concentration of oxidative stress metabolites in the intestine. Thirdly, we found six metabolites that could rescue oocyte quality and early embryonic development, among which LCA of 30 mg/kg and NorDCA of 15 mg/kg had the best rescue effect.These findings confirm the link between ovarian function and gut microbiota regulation by microbial metabolites and have potential value for improving ovary function.
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