Roya Askarian - medical biochemistry

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. The main epigenetic mechanisms of gene expression regulation are represented by DNA methylation, histone modifications, and small, non-coding RNAs. 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(impairment of male fertility due to alterations in sperm number and morphology), (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. Recent studies have demonstrated the presence of unique consensus DNA sequence motifs, zinc finger motifs, and G-quadruplex sequences in transgenerational DMR in sperm, which, by the interaction of molecular factors, could induce alterations of the chromatin structure and accessibility of proteins with DNA methyltransferases altering de novo DNA methylation patterns. Several environmental and lifestyle factors (stress, physical activity, alcohol intake, smoke, shift work) are known to affect male and female fertility , and in many cases, they have been shown to influence the occurrence of epigenetic modifications with implications for human diseases. It can be suggested that in the next future, the study of epigenetics and epigenomics will likely represent a crucial step in the diagnostic workup of the infertile male, especially in cases submitted to ART, where it will be necessary to select adequately functional sperm to avoid the epigenetic alteration impact on the procedure. Surprisingly, seminal plasma may affect offspring independently of sperm, by stimulating the production of embryotrophic cytokines and growth factors by the female reproductive tract. The alteration of this process induces abnormal fat deposition and metabolic phenotype in the offspring, particularly in the males.Most importantly, the possibility that paternal lifestyle could affect the health of the offspring during lifetime opens a novel and exacting scenario in the prevention of common, late onset diseases. 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.

Male infertility, Gametogenesis, Epigenetics, DNA methylation, Transgenerational effect