The role of epigenetics in spermatogenesis

Abstract

Male germ cells have a unique morphology and function to facilitate fertilization. Sperm deoxyribonucleic acid (DNA) is highly condensed to protect the paternal genome during transfer from male to oocyte. Sperm cells undergo extensive epigenetic modifications during differentiation to become a mature spermatozoon. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling are substantial regulators of spermatogenesis. DNA hypermethylation is associated with gene silencing. Meanwhile, hypomethylation is associated with gene expression. In sperm cells, promoters of developmental genes are highly hypomethylated. Proper DNA methylation is essential for embryo development. Histone modifications are chemical modifications that change the DNA-binding capacity of histones and the accessibility of regulatory factors to the DNA, thereby altering gene expression. Phosphorylation, methylation, acetylation, and ubiquitination are primary modifications of lysine and serine residues on histone tails. In addition to somatic histones, testis-specific histone variants are expressed, including histone H2B in mature sperm. The replacement of histones with protamines is a crucial step in spermatogenesis. Histone hyperacetylation induces a loose chromatin structure and facilitates topoisomerase-induced DNA strand breaks. As a result, histones are replaced with transition proteins. Next, the transition proteins are replaced with protamines that induce compaction of sperm DNA. This review provides an overview of epigenetic changes during spermatogenesis.

Smoking-induced genetic and epigenetic alterations in infertile men

“…Epigenetics is the study of mitotically and/or meiotically heritable modifications regulating genome activity without any impact on DNA sequences. Proper regulation of epigenetic processes including DNA methylation, histone modifications and nuclear protein transitions, and noncoding RNAs during gonadal development and spermatogenesis is crucial for the maintenance of embryonic development and normal sperm function (Guerrero‐Bosagna & Skinner, ; Gunes & Kulac, ; Rajender, Avery, & Agarwal, ). Fertilisation status and sperm function may be affected by changes during the epigenetic process.…”

Independent validation of body fluid-specific CpG markers and construction of a robust multiplex assay

“…However, marker SE2, showing hypermethylation of semen only, was chosen over DACT1. Due to epigenetic reprogramming, spermatozoa are expected to be hypomethylated [21] making marker SE2 even more interesting for semen identification since it is a rare example of hypermethylation.…”

Casein‐ and pea‐enriched high‐protein diet can take care of the reprotoxic effects of arsenic in male rats

“…Moreover, the chromatin condensation, which is considered a valuable index of sperm DNA quality (Auger, Mesbah, Huber, & Dadoune, 1990), also got adversely affected. In the chromatin condensation process, typically, the histones are swapped with transition proteins, which are further threaded with protamines essential for compaction of sperm DNA in the mature spermatozoa (Gunes & Kulac, 2013). Aniline blue primarily stains the lysine‐rich histones of immature spermatozoa, but not the arginine‐ and cysteine‐rich protamines and, therefore, detects the degree of chromatin compaction or maturation.…”