Epigenetic Modifications, A New Approach to Male Infertility Etiology: A Review.

Recent studies have indicated that epigenetic alterations are critical for normal function and development of spermatozoa during the fertilization process. This review will focus on the latest advances in epigenome profiling of the chromatin modifications during sperm development, as well as the potential roles of epigenetic mechanisms in the context of male infertility. In this review, all data were collected from published studies that considered the effect of epigenetic abnormalities on human spermatogenesis, sperm parameters quality, fertilization process, embryo development and live births. The database PubMed was searched for all experimental and clinical studies using the Keywords "epigenetic modifications", "male infertility", "spermatogenesis", "embryo development" and "reproductive function". Post-translational modifications of histone, DNA methylations and chromatin remodeling are among the most common forms of epigenetic modifications that regulate all stages of spermatogenesis and fertilization process. Incorrect epigenetic modifications of certain genes involved in the spermatogenesis and sperm maturation may be a main reason of male reproductive disorder and infertility. Most importantly, abnormal patterns of epigenetic modifications or transgenerational phenotypes and miRNAs expression may be transmitted from one generation to the next through assisted reproductive techniques (ART) and cause an increased risk of birth defects, infertility and congenital anomalies in children. Epigenetic modifications must be considered as a one of the main factors of unexplained male infertility etiology. Due to high risk of transmitting incorrect primary imprints to offspring, there is a need for more research into epigenetic alterations in couples who benefit of ART support.

Regulatory Functions of MicroRNAs in Male Reproductive Health: A New Approach to Understanding Male Infertility.

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs (ncRNAs) that play critical roles in regulation of gene expression, especially at posttranscriptional level. Over the past decade, the degree to which miRNAs are involved in male infertility has become clear. They are expressed in a cell- or phase-specific manner during spermatogenesis and play crucial role in male reproductive health. Therefore, dysregulation of miRNAs in testicular cells can be considered as a molecular basis for reproductive failure and male infertility. The abnormal expression pattern of miRNAs can be transmitted to the offspring via assisted reproductive techniques (ART) and results in the birth of children with a higher risk of infertility, congenital abnormalities, and morbidity. This review expounds on the miRNAs reported to play essential roles in somatic cells development, germ cells differentiation, steroidogenesis, normal spermatogenesis, sperm maturation, and male infertility, as well as emphasizes their importance as minimally invasive biomarkers of male infertility.