Department of Pharmacy, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Commun Biol. 2024 Nov 19;7(1):1535. doi: 10.1038/s42003-024-07233-y.
Dietary modifications to overcome infertility have attracted attention; however, scientifically substantiated information on specific dietary components affecting fertility and their mechanisms is limited. Herein, we investigated diet-induced, reversible infertility in female mice lacking the heterodimer of ATP-binding cassette transporters G5 and G8 (ABCG5/G8), which functions as a lipid exporter in the intestine. We found that dietary phytosterols, especially β-sitosterol and brassicasterol, which are substrates of ABCG5/G8, have potent but reversible reproductive toxicities in mice. Mechanistically, these phytosterols inhibited ovarian folliculogenesis and reduced egg quality by enhancing polycomb repressive complex 2-mediated histone H3 trimethylation at lysine 27 in the ovary. Clinical analyses showed that serum phytosterol levels were significantly and negatively correlated with the blastocyst development rate of fertilized eggs in women undergoing in vitro fertilization, suggesting that phytosterols affect egg quality in both humans and mice. Thus, avoiding excessive intake of certain phytosterols would be beneficial for female reproductive health.
饮食调整以克服不孕已引起关注；然而，关于影响生育力的特定饮食成分及其机制的科学依据信息有限。在此，我们研究了缺乏作为肠道脂质外排体的 ABC 转运蛋白 G5 和 G8（ABCG5/G8）异二聚体的雌性小鼠的饮食诱导的、可逆转的不孕。我们发现膳食植物甾醇，尤其是 ABCG5/G8 的底物β-谷甾醇和菜油甾醇，对小鼠具有潜在但可逆转的生殖毒性。在机制上，这些植物甾醇通过增强多梳抑制复合物 2 介导的组蛋白 H3 在卵巢中的赖氨酸 27 处的三甲基化，抑制了卵泡发生并降低了卵子质量。临床分析表明，进行体外受精的妇女的血清植物甾醇水平与受精卵的囊胚发育率呈显著负相关，这表明植物甾醇会影响人和小鼠的卵子质量。因此，避免过量摄入某些植物甾醇将有益于女性生殖健康。
