Endometrial aging is accompanied by H3K27ac and PGR loss by Yue Wang & Ping Zhou & Hongying Shan & Xiyao Liu & Ming Cheng & Zhenhong Ye & Xiunan Chen & Baoying Liao & Tianliu Peng & Chenxi Xiao & Ziying Huang & Yunshu Dong & Yang Yu & Heng Pan & Rong Li instant download

Endometrial aging is accompanied by H3K27ac and PGR loss by Yue Wang & Ping Zhou & Hongying Shan & Xiyao Liu & Ming Cheng & Zhenhong Ye & Xiunan Chen & Baoying Liao & Tianliu Peng & Chenxi Xiao & Ziying Huang & Yunshu Dong & Yang Yu & Heng Pan & Rong Li instant download

Whether and how endometrial aging afects fertility remains unclear. In our in-house clinical cohort at the Center for Reproductive Medicine of Peking University Third Hospital (n = 1,149), we observed adverse pregnancy outcomes in the middle-aged group after excluding aneuploid embryos, implying the negative impact of endometrial aging on fertility. To understand endometrial aging, we performed comprehensive transcriptomic profling of the mid-secretory endometrium of young (<35 years) and middle-aged (≥35 years) patients. This analysis revealed that H3K27ac loss is linked to impaired endometrial receptivity in the middle-aged group. We eliminated H3K27ac in young human endometrial stromal cells and observed reduced progesterone receptor (PGR), a critical regulator of endometrial receptivity. Lastly, we validated the association between H3K27ac/PGR loss and uterine aging in a mouse model. Our fndings establish H3K27ac as a critical regulator of PGR and demonstrate that endometrial H3K27ac loss is associated with aging-related fertility decline. This work provides valuable insights into enhancing the safety and efcacy of assisted reproductive technologies in future clinical practices.