Replication-independent DNA methylation dynamics during post-testicular sperm maturation

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It has become apparent that sperm are extensively remodeled during epididymal transit, with ongoing changes to the protein and RNA content of maturing sperm. In addition, an increasing number of studies have shown that epigenetic information is modified during the process of sperm maturation. During the first year of my PhD studies, I have discovered that cytosine methylation patterns are surprisingly dynamic during sperm maturation in the epididymis. Using whole genome bisulfite sequencing (WGBS), I identified widespread changes in DNA methylation as sperm move from the testes through the caput, corpus, and cauda of the epididymis. Given that sperm are a highly methylated and condensed cell type, it is surprising and novel that epididymal transit results in any DNA methylation reprogramming of sperm. I aim to address the question of how DNA methylation changes occur between different sperm populations. My approach is to recapitulate maturation-associated cytosine methylation dynamics in vitro to understand the mechanism by which these changes are occurring. Resolving what these changes mean for potential offspring and determining the mechanisms and factors leading to changes in methylation will have significant implications for both assisted reproduction, and for understanding how a father's environment impacts his children's well being.