Endometrial aging is accompanied by H3K27ac and PGR loss.

IF 17 Q1 CELL BIOLOGY

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-05-20 DOI:10.1038/s43587-025-00859-5

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

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Abstract

Whether and how endometrial aging affects 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 profiling 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 findings 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 efficacy of assisted reproductive technologies in future clinical practices.

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子宫内膜衰老伴随着H3K27ac和PGR的丢失。

子宫内膜老化是否以及如何影响生育能力仍不清楚。在我们北京大学第三医院生殖医学中心的内部临床队列中（n = 1149），我们观察到中年人在排除非整倍体胚胎后的不良妊娠结局，这表明子宫内膜老化对生育能力有负面影响。为了了解子宫内膜老化，我们对年轻(

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