Ankolkar Mandar, Deshpande Sharvari S, Balasinor Nafisa H
Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
Andrologia. 2018 Oct;50(8):e13060. doi: 10.1111/and.13060. Epub 2018 Jun 19.
Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis. Endocrine disruption has been previously shown to affect reproductive outcome and sperm DNA methylation. This study aims to decipher the possibility of changes in nucleosome occupancy in sperm chromatin, induced by tamoxifen (selective oestrogen receptor modulator) and cyproterone acetate (androgen antagonist). We used next-generation sequencing approach (MNase-Seq) to identify changes in the nucleosome landscape of the spermatozoa. We demonstrated that endocrine disruption affects nucleosome occupancy at critical regions of the genome and many of them harbour genes relevant for embryogenesis. This study emphasises that environmental factors could affect embryo development by way of modulating male epigenetic factors.
精子染色质包装是一种非常复杂且受到高度调控的现象。虽然大部分精子染色质被鱼精蛋白取代，但仍有一些保留在核小体中。最近人们认识到，这些核小体是有意保留的，可能在胚胎发育的早期阶段对基因表达有贡献。先前已表明内分泌干扰会影响生殖结果和精子DNA甲基化。本研究旨在解读他莫昔芬（选择性雌激素受体调节剂）和醋酸环丙孕酮（雄激素拮抗剂）诱导精子染色质中核小体占有率变化的可能性。我们使用下一代测序方法（MNase-Seq）来识别精子核小体图谱的变化。我们证明内分泌干扰会影响基因组关键区域的核小体占有率，其中许多区域含有与胚胎发育相关的基因。这项研究强调环境因素可能通过调节男性表观遗传因素来影响胚胎发育。
