Epigenetic regulation by DNA methylation, histone modifications and chromatin remodeling complexes in controlling spermatogenesis and their dysfunction with male infertility

作者：Yinghong Cui, Jiakun Deng, Yueling Zhang, Li Du, Fen Jiang, Chunyun Li, Wei Chen, Haibin Zhang, Zuping He · 发表于：Cellular and Molecular Life Sciences · 年份：2025 · DOI：10.1007/s00018-025-05831-5 · 被引用次数：14 · 研究领域：Epigenetics and DNA Methylation、Sperm and Testicular Function、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

As key factors of cellular development, epigenetic regulation can accurately control gene expression through multiple manners, e.g., DNA methylation, histone modification, and chromatin remodeling complexes (CRCs). Epigenetic factors play pivotal roles in various kinds of cell processes, including cell proliferation, differentiation, and apoptosis, and diseases may be resulted from their dysfunction. Spermatogenesis refers to the complex process by which spermatogonial stem cells (SSCs) self-renew and differentiate into the differentiating spermatogonia that further develop to spermatocytes and mature spermatids. Significantly, epigenetic regulation has recently been shown to mediate fate determinations of SSCs to ensure normal spermatogenesis. Interestingly, much progress has recently been made in epigenetic regulation and their dysfunction in controlling spermatogenesis and male infertility, respectively. In this review, we address the dynamic expression patterns, functions and mechanisms of DNA methylation, histone modification, and CRCs in mediating the development of SSCs and spermatogenesis, and we also discuss the association between epigenetic dysfunction and male infertility. We further point out the perspectives in epigenetic regulation on human spermatogenesis. Our review on the in-depth analysis of epigenetic regulatory mechanisms in normal and abnormal spermatogenesis not only helps us better understand the etiology of male infertility but also provides novel tar...