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Review
. 2025 Jun;17(8):541-554.
doi: 10.1080/17501911.2025.2491298. Epub 2025 Apr 14.

Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects

Ryosuke Kobayashi  1 , Izuho Hatada  2   3
Affiliations
Review

Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects

Ryosuke Kobayashi et al. Epigenomics. 2025 Jun.

Abstract

Endometrial function, crucial for successful embryo implantation, is significantly influenced by epigenetic regulation. This review investigates the crucial roles of DNA methylation, histone modifications, chromatin remodeling, and RNA methylation in endometrial receptivity and implantation, based on a survey of recent literature on knockout mouse models with implantation defects. These models illuminate how epigenetic disruptions contribute to implantation failure, a significant human reproductive health concern. DNA methylation and histone modifications modulate endometrial receptivity by affecting gene silencing and chromatin structure, respectively. Chromatin remodeling factors also play a critical role in endometrial dynamics, influencing gene expression. Furthermore, RNA methylation emerges as critical in implantation through transcriptional and translational control. While human studies provide limited epigenetic snapshots, mouse models with suppressed epigenetic regulators reveal direct causal links between epigenetic alterations and implantation failure. Understanding these epigenetic interactions offers potential for novel therapies addressing reproductive disorders.

Keywords: DNA methylation; Embryo implantation; RNA methylation; chromatin remodeling; endometrium; histone modifications; infertility; mouse models.

Plain language summary

For a pregnancy to start, an embryo must implant in the uterus. The uterus lining (endometrium) must be prepared for embryo in advance, like soil for a seed. “Epigenetic switches” control how the endometrium develops by turning genes “on” or “off.” Studying mice with implantation problems helps us understand these epigenetic switches. This review, summarizes recent research on these mice, highlighting the importance of epigenetic switches for successful implantation. These knowledges could lead to new fertility treatments.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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