Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

Abstract

The correlation between epigenetics and human reproduction represents a very interesting field of study, mainly due to the possible transgenerational effects related to epigenetic modifications of male and female gametes. In the present review, we focused our attention to the role played by epigenetics on male reproduction, evidencing at least four different levels at which sperm epigenetic modifications could affect reproduction: (1) spermatogenesis failure; (2) embryo development; (3) outcome of assisted reproduction technique (ART) protocols, mainly as concerning genomic imprinting; and (4) long-term effects during the offspring lifetime. The environmental agents responsible for epigenetic modifications are also examined, suggesting that the control of paternal lifestyle prior to conception could represent in the next future a novel hot topic in the management of human reproduction.

Keywords: DNA methylation; Epigenetics; Gametogenesis; Male infertility; Transgenerational effect.

Fig. 1

Epigenetic modifications during spermatogenesis. During the different steps of spermatogenesis, several epigenetic modifications involving DNA methylations and histone modifications occur. (1) PGCs undergo a process of demethylation involving DNA (with erasure of genomic imprinting) and histones (namely, K4 and K9 residues of H3). Also, a process of H4 deacetylation is present. DNMT3A, DNMT3B, and DNMT3L are expressed at this time. (2) In spermatogonia, a progressive DNA methylation occurs, with establishment of paternal methylation. (3) In spermatocytes, H3K9 and H3K4 methylation is observed. (4) In round spermatids, H4 becomes hyperacetylated, DNMT1 is expressed, and the transition from histones to TPs occurs. (5) Elongated spermatids show a maintenance of DNA methylation, together with H3K9 demethylation. The transition from TPs to protamines occurs at this step. (6) In spermatozoa, the genomic imprinting is maintained

Fig. 2

Epigenetic alterations induced by lifestyle and environmental factors (diet, smoking, radiation, alcohol consumption, etc.) can have substantial effects on the sperm function. As a first consequence, these modifications can induce sperm alterations leading to impairment of male fertility. When fertilization occurs, spontaneously or by ART, transgenerational epigenetic effects can be observed, in details leading to (1) alterations of embryo development, (2) congenital diseases at birth, and (3) late onset diseases (obesity, hypertension, diabetes, etc.) in the adult life