Epigenetic processes in the male germline
Alan M. O’Doherty A C and Paul A. McGettigan B
+ Author Affiliations
- Author Affiliations
A School of Medicine and Medical Sciences, Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
B School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
C Corresponding author. Email: alan.odoherty@ucd.ie
Reproduction, Fertility and Development 27(5) 725-738 https://doi.org/10.1071/RD14167
Submitted: 20 May 2014 Accepted: 1 August 2014 Published: 9 September 2014
Abstract
Sperm undergo some of the most extensive chromatin modifications seen in mammalian biology. During male germline development, paternal DNA methylation marks are erased and established on a global scale through waves of demethylation and de novo methylation. As spermatogenesis progresses, the majority of the histones are removed and replaced by protamines, enabling a tighter packaging of the DNA and transcriptional shutdown. Following fertilisation, the paternal genome is rapidly reactivated, actively demethylated, the protamines are replaced with histones and the embryonic genome is activated. The development of new assays, made possible by high-throughput sequencing technology, has resulted in the revisiting of what was considered settled science regarding the state of DNA packaging in mammalian spermatozoa. Researchers have discovered that not all histones are replaced by protamines and, in certain experiments, various species of RNA have been detected in what was previously considered transcriptionally quiescent spermatozoa. Most controversially, several groups have suggested that environmental modifications of the epigenetic state of spermatozoa may operate as a non-DNA-based form of inheritance, a process known as ‘transgenerational epigenetic inheritance’. Other developments in the field include the increased focus on the involvement of short RNAs, such as microRNAs, long non-coding RNAs and piwi-interacting RNAs. There has also been an accumulation of evidence illustrating associations between defects in sperm DNA packaging and disease and fertility. In this paper we review the literature, recent findings and areas of controversy associated with epigenetic processes in the male germline, focusing on DNA methylation dynamics, non-coding RNAs, the biology of sperm chromatin packaging and transgenerational inheritance.
Additional keywords: chromatin, DNA methylation, gametogenesis, histones, non-coding RNA, spermatogenesis, spermatozoa, transgenerational inheritance.
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