Fertility Preservation Lab, Guangdong-Hong Kong Metabolism and Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China.
Clin Transl Med. 2023 Oct;13(10):e1236. doi: 10.1002/ctm2.1236.
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.
揭示肠道微生物群及其代谢物是否与昼夜节律紊乱导致的卵母细胞质量下降相关，并寻找改善卵母细胞质量的可能方法。
建立了持续光照暴露的小鼠模型。分析卵母细胞质量、胚胎发育、微生物代谢物和肠道微生物群。进行肠道微生物代谢物的胃内给药，以确认肠道微生物群与卵母细胞质量和胚胎发育的关系。
首先，我们发现持续光照暴露的小鼠卵母细胞质量和胚胎发育下降。通过代谢组学分析和 16S rDNA-seq，我们发现由于胆酸（如石胆酸）的显著减少，维生素 D 的肠道吸收能力降低，这与 Turicibacter 的丰度增加显著相关。随后，血液中的抗苗勒管激素（AMH）激素和卵泡液中的褪黑素浓度降低，这是卵母细胞质量和早期胚胎发育下降的主要原因，而注射维生素 D3（VD3）可得到挽救。其次，褪黑素通过增加石胆酸的浓度和降低肠道氧化应激代谢物的浓度来挽救卵母细胞质量和胚胎发育。第三，我们发现了 6 种可挽救卵母细胞质量和早期胚胎发育的代谢物，其中 30mg/kg 的石胆酸和 15mg/kg 的 NorDCA 具有最佳的挽救效果。
这些发现证实了卵巢功能与肠道微生物群通过微生物代谢物调节之间的联系，并为改善卵巢功能具有潜在价值。
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