DNA methylation in bull spermatozoa: evolutionary impacts, interindividual variability, and contribution to the embryo

Abstract

The DNA methylome of spermatozoa results from a unique epigenetic reprogramming crucial for chromatin compaction and the protection of the paternal genetic heritage. Although bull semen is widely used for artificial insemination (AI), little is known about the sperm epigenome in cattle. The purpose of this review is to synthetize recent work on the bull sperm methylome in light of the knowledge accumulated in humans and model species. We will address sperm-specific DNA methylation features and their potential evolutionary impacts, with particular emphasis on hypomethylated regions and repetitive elements. We will review recent examples of interindividual variability and intra-individual plasticity of the bull sperm methylome as related to fertility and age, respectively. Finally, we will address paternal methylome reprogramming after fertilization, as well as the mechanisms potentially involved in epigenetic inheritance, and provide some examples of disturbances that alter the dynamics of reprogramming in cattle. Because the selection of AI bulls is closely based on their genotypes, we will also discuss the complex interplay between sequence polymorphism and DNA methylation, which represents both a difficulty in addressing the role of DNA methylation in shaping phenotypes and an opportunity to better understand genome plasticity.

Sperm DNA Hypomethylation Proximal to Reproduction Pathway Genes in Maturing Elite Norwegian Red Bulls

“…Considering uniform condition and environment for raising and feeding the bulls, it is least likely that individual differences in DNA methylation here is driven by environmental factors. However, in addition to environmental factors, it has been shown that individual differences in sperm DNA methylation may be explained by epigenetic polymorphism phenomenon and interindividual genetic diversity (Kiefer and Perrier, 2019). In agreement with global sperm DNA methylome results presented here, previous research reported that DNA methylation levels in bull sperm is dynamic during puberty, becoming stable after the age of 1 year (Lambert et al, 2018).…”

“…For instance, it has been shown that sperm morphology, concentration and motility positively correlated with age in young tropical composite bulls (Fortes et al, 2012) and Austrian Simmental bulls (Fuerst-Waltl et al, 2006). Although several studies reported low methylation levels in different genomic features of bull sperm cells (Perrier et al, 2018;Zhou et al, 2018;Kiefer and Perrier, 2019), the methylation level is dynamic and recent evidence suggests that the bull sperm methylome correlates with age (Lambert et al, 2018).…”

Accelerating Onset of Puberty Through Modification of Early Life Nutrition Induces Modest but Persistent Changes in Bull Sperm DNA Methylation Profiles Post-puberty

“…After puberty and during spermatogenesis, DNA methylation patterns are essentially maintained, whereas profound rearrangements of DNA packaging (histone to protamine replacement, addition of sperm-specific histone variants, and histone post-translational modifications), and significant changes of sperm non-coding RNA content can be observed (Carrell, 2012;McSwiggin and O'Doherty, 2018). Any alterations of these dynamic epigenetic processes by intrinsic or environmental factors can potentially affect fertility, as well as influence the phenotype of the offspring (Chavatte-Palmer et al, 2016;Champroux et al, 2018;Kiefer and Perrier, 2020).…”

Role of Long Chain Fatty Acids in Developmental Programming in Ruminants

“…It has been described that the ruminants DNA is methylated at the 5-position of cytosine residues predominantly within guanine-cytosine (CpG) dinucleotides such that about 60–80% of CpGs within the genome are methylated [ 41 ]. This definition of epigenetics does not apply to spermatozoa, which are transcriptionally inactive and represent the ultimate form of cell differentiation, destined to give rise to a new individual after fertilization of an oocyte and not to daughter cells with a similar phenotype [ 42 ]. The differentiation of male germ cells into functional spermatozoa requires a unique epigenetic reprogramming involving large-scale DNA methylation changes, the replacement of most histones by protamines, and an accumulation of specific non-coding RNAs [ 32 ].…”

“…The differentiation of male germ cells into functional spermatozoa requires a unique epigenetic reprogramming involving large-scale DNA methylation changes, the replacement of most histones by protamines, and an accumulation of specific non-coding RNAs [ 32 ]. Even though transcription is barely detectable in mature sperm cells, the male germline differentiation programmed is orchestrated by a dynamic sequence of transcriptional regulations that are directly reliant on epigenetic reprogramming [ 42 ]. The biological processes described previously has been recognized with evidence supporting the biological epigenetic process [ 41 ]; however, a lack of evidence of the role of FA supplementation and its effects on the genome-wide DNA methylation profiles are still scarce and limited [ 30 ].…”