Potential roles of epigenetic modifications in male reproductive development and function: a review on new approach for etiology of infertility

Document Type : Review Article


1 Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran

2 Islamic Azad University, Pharmaceutical Sciences Branch, Tehran, Iran

3 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Chemical Injuries Research Center, Systems biology and poisonings institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Department of Biochemistry, Islamic Azad University, Sari Branch, Sari, Iran, I.R. Iran

6 Vanak Square, Molla Sadra Street,Chemical Injuries Research Center, Baqiatallah University of Medical Sciences



Background: Recent studies have indicated that epigenetic alterations are critical for normal function and development of spermatozoa during fertilization process. This review will focus on the latest advances in epigenome profiling of the chromatin modifications during sperm development, as well as the potential roles of epigenetic mechanisms in the context of male infertility.

Methods: We performed a review of published studies considering the effect of epigenetic abnormalities on human spermatogenesis, sperm parameters quality, fertilization process, embryo development and live births. PubMed was searched for all experimental and clinical studies using the Keywords “epigenetic modifications”, “male infertility”, “spermatogenesis”, “embryo development” and “reproductive function”.

Results: Post-translational modifications of histone, DNA methylations, chromatin remodeling or rearrangement, and expression patterns of different non-coding RNAs (ncRNAs) are the most important types of epigenetic modifications that regulate spermatogenesis and fertilization process. Therefore, incorrect epigenetic modifications in testicular cells may be a molecular mechanism of male reproductive disorder and infertility. More importantly, abnormal patterns of epigenetic modifications or transgenerational phenotypes and miRNAs expression may be transmitted from one generation to the next through assisted reproductive techniques (ART) and cause increased risk of birth defects, infertility and congenital anomalies in children.

Conclusion: Epigenetics modifications must be considered as one of the main factors for the etiology of unexplained male infertility because infertile men may carry a higher risk of transmitting incorrect primary imprints to their offspring, indicating the need for more research into epigenetic alterations in persons undergoing ART.