Chapter 21 - Reproductive Disease Epigenetics

Abstract

Differentiation of the male and female gametes involves extremely well-regulated epigenetic and chromatin changes. An appropriate complement of the imprinted genes in the male and female gametes is essential to allow appropriate epigenetic regulation and development of the embryo. Therefore any perturbations of imprinting during the reproductive process have the potential to result in male or female infertility and/or subsequent anomalies. Epidemiological data in the human population and studies in animal models suggest that environmental exposures and diet may result in epigenetic changes, which may be linked to common multifactorial disorders and infertility. An abnormal pattern of sperm DNA methylation, sperm RNA content, and sperm chromatin gene poising has been reported in some infertile men. Also altered epigenetics is being detected in female reproductive anomalies such as polycystic ovary syndrome, endometriosis, and placental syndromes. Fortunately, reproductive dysfunction can be efficiently treated using assisted reproduction techniques. However, there are currently some concerns about whether the potential epigenetic immaturity of the gametes and the in vitro conditions used might result in epigenetic anomalies. While the vast majority of assisted reproduction children seem to be healthy, a slightly higher incidence of infants born with minor or major phenotypic or metabolic disturbances, or with known epigenetic syndromes such as Beckwith–Widemann, is under study. This chapter reviews the physiological epigenetic changes during reproduction and development, describes the main alterations associated with infertility or offspring defects potentially linked to epigenetics, and outlines the research frontiers currently being explored.