Infertility is a complex condition influenced by genetic and biological factors. In men, it is often caused by abnormalities in chromosome number or structure, alterations in DNA structure, specific gene mutations, or missing segments of the Y chromosome. Recent studies have also highlighted the impact of epigenetic mechanisms-such as DNA methylation, histone modifications, and noncoding RNAs-on gene function and fertility. Abnormal methylation patterns, particularly in genes such as DNMT3A/B/L, H19, MEST, SOX30, and those involved in the piRNA pathway, have been linked to poor sperm production and reduced fertility. These epigenetic changes can lower sperm quality, impair embryo health, and decrease the chances of success with fertility treatments. The role of biological and epigenetic factors in female reproduction is more limited. This narrative review aims to examine well-established genetic and epigenetic mechanisms associated with infertility, with a focus on key molecular pathways and regulatory processes. A literature review was conducted to summarize the most relevant and recent publications addressing genetic and epigenetic mechanisms as contributing factors to human infertility.
Keywords: epigenetics; female infertility; male infertility; sperm DNA methylation; sperm non-coding RNAs.
Genetics and epigenetics of infertility Infertility is a complex health issue that can be caused by both genetic and biological factors. In men, common causes include problems with the number or structure of chromosomes, changes in DNA, specific gene mutations, or missing pieces of the Y chromosome. Research also shows that epigenetic mechanisms—changes that affect how genes work without altering the DNA sequence—play a role in fertility. These include DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). Abnormal methylation in certain genes, such as DNMT3A/B/L H19, MEST, SOX30, and genes involved in the piRNA pathway, has been linked to poor sperm production and reduced fertility. Such changes can lower sperm quality, harm embryo health, and reduce the success rates of fertility treatments. The influence of genetic and epigenetic factors in female reproduction was also reviewed, although there is less data available. This article summarizes current knowledge on the most important genetic and epigenetic mechanisms involved in infertility, focusing on key molecular pathways and regulatory processes. It is based on a review of recent and relevant scientific publications on this topic.
© The Author(s), 2025.