Male Infertility: An Epigenetic Perspective

Abstract

Besides known genetic and environmental factors, research over the last two decades has shed light on several epigenetic mechanisms and their association with male infertility. The male germ line undergoes extensive epigenetic remodeling throughout fetal to adult life and is thus susceptible to environmental factors that can affect fertility. During fetal life, the primordial germ cells undergo removal of epigenetic marks (demethylation) followed by re-establishment of these marks according to the sex of the fetus, at the time of gonadal differentiation. Extensive programming of the epigenome occurs during the various phases of spermatogenesis, i.e., mitosis, meiosis, and spermiogenesis, leading to haploid-condensed spermatozoa with protamines as the major nucleoproteins. Shortly after fertilization, the sperm chromatin decondenses and the protamines are replaced by histones. The male pronucleus undergoes active demethylation. One such epigenetic phenomenon, genomic imprinting resulting in monoallelic expression of genes depending on the parent of origin, is involved in early embryogenesis. Aberrant methylation pattern of imprinting control region (ICR) of imprinted genes in the spermatozoa is associated with altered sperm morphology, count, and motility. This chapter provides a comprehensive overview of the epigenetic changes affecting spermatogenesis and male fertility.