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Updated: May 23, 2025

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
Endometrial aging is accompanied by H3K27ac and PGR loss
Yue Wang1,2,3,4, Ping Zhou1,2,3,4, Hongying Shan1,2,3,4
1State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
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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