Methionine regulates maternal-fetal immune tolerance and endometrial receptivity by enhancing embryonic IL-5 secretion

作者：Shuang Cai, Bangxin Xue, Siyu Li, Xinyu Wang, Xiangzhou Zeng, Xiangzhou Zeng, Zhekun Zhu, Xinyin Fan, Yijin Zou, Haitao Yu, Shiyan Qiao, Xiangfang Zeng, Xiangfang Zeng · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.115291 · 被引用次数：17 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Birth, Development, and Health

Endometrial receptivity and maternal-fetal immune tolerance are two crucial processes for a successful pregnancy. However, the molecular mechanisms of nutrition involved are largely unexplored. Here, we showed that maternal methionine supply significantly improved pregnancy outcomes, which was closely related to interleukin-5 (IL-5) concentration. Mechanistically, methionine induced embryonic IL-5 secretion, which enhanced the conversion of CD4 + T cells to IL-5 + Th2 cells in the uterus, thereby improving maternal-fetal immune tolerance. Meanwhile, methionine-mediated IL-5 secretion activated the nuclear factor κB (NF-κB) pathway and enhanced integrin αvβ3 expression in endometrial cells, which improved endometrial receptivity. Further, methionine strongly influenced the DNA methylation and transcription levels of the transcription factor eomesodermin ( Eomes ), which bound directly to the IL-5 promoter region and inhibited IL-5 transcription. Methionine modulated IL-5 transcription, maternal-fetal immune tolerance, and endometrial receptivity via its effects on Eomes . This study reveals the crucial functions of methionine and IL-5 and offers a potential nutritional strategy for successful pregnancy.