Epigenetic alterations in sperm cells from infertile patients

Abstract

Epigenetic modifications regulate chromatin conformation and transcription factor accessibility to regulatory regions of the genome, controlling gene expression without altering the DNA sequence itself and being stably transmitted throughout cell divisions. One of the most well studied epigenetic marks is DNA methylation, which controls the monoallelic, parental-dependent expression of imprinted genes. Paternal imprinting marks are established in the male germ line, so that the mature gametes - the spermatozoa - transmit correct imprints to the future embryo. Anomalies in the establishment of imprinting marks can affect embryonic and placental development and result in the birth of children carrying imprinting syndromes, such as Silver-Russell and Beckwith-Wiedemann syndromes. Here we review the literature on the observations of imprinting errors in the male gamete, in the context of disturbances in spermatogenesis resulting in male infertility, focusing on the evidence described by our group and others. We provide a clinical perspective on the implementation of sperm methylation analysis as a tool to improve diagnostic and therapeutic strategies in Assisted Reproduction Treatments (ART) and highlight the importance of understanding the molecular mechanisms underlying spermatogenic defects and male infertility.