Chapter 5 - Epigenetic Changes in the Paternal Germline

Abstract

Germ cells function to transmit genetic information from one generation to the next. In mammals, mature male germ cells are uniquely specialized in order to overcome the challenges associated with achieving fertilization within the female reproductive tract, and to provide a single chromosomal complement to offspring. Male germ cell development, including primordial germ cell and gonocyte development, and spermatogenesis, entails numerous epigenetic changes, such as DNA methylation, histone modification, histone variant incorporation, and small-RNA mediated processes, which promote meiosis and structural remodeling. Moreover, male germ cells must also be epigenetically reset, or reprogrammed, in order to establish a new generation. During embryonic development, primordial germ cells are cleared of somatically associated epigenetic marks, and new marks are established that are sex-specific as well as germline-specific. Additionally, after fertilization occurs, the paternal pronucleus is epigenetically reprogrammed in early zygotic stages, allowing for embryonic totipotency. While epigenetic reprogramming events are nearly genome-wide, some modifications are retained at select loci. Thus, it is possible that epigenetic information is transgenerationally inherited via the paternal germline. This chapter provides a comprehensive review on known epigenetic changes that occur during male germ cell development, as well as questions that remain unanswered in the field. Finally, clinical implications for altered epigenetic states are discussed.