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

很明显，随着成熟精子蛋白质和RNA含量的不断变化，精子在附睾运输过程中会发生广泛的重塑。此外，越来越多的研究表明，表观遗传信息在精子成熟过程中会发生改变。在我博士研究的第一年，我发现胞嘧啶甲基化模式在附睾精子成熟期间是令人惊讶的动态变化。使用全基因组亚硫酸盐测序(WGBS)，我发现随着精子从睾丸通过附睾头、附睾体和附睾尾，DNA甲基化发生了广泛的变化。鉴于精子是一种高度甲基化和浓缩的细胞类型，附睾会导致精子的DNA甲基化重新编程，这是令人惊讶和新奇的。我的目标是解决DNA甲基化如何在不同精子群体之间发生变化的问题。我的方法是在体外总结与成熟相关的胞嘧啶甲基化动力学，以了解这些变化发生的机制。解决这些变化对潜在后代的意义并确定其机制 而导致甲基化变化的因素将对辅助生殖和理解父亲的环境如何影响孩子的幸福有着重要的影响。

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.