a Center for Reproductive Biology, School of Biological Sciences , Washington State University , Pullman , WA , USA.
b Department of Biology , University of Texas at San Antonio , San Antonio , TX , USA.
Epigenetics. 2019 Jul;14(7):721-739. doi: 10.1080/15592294.2019.1614417. Epub 2019 May 13.
A number of environmental factors from nutrition to toxicants have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. This requires alterations in the germline (sperm or egg) epigenome. Previously, the agricultural fungicide vinclozolin was found to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate the developmental origins of the transgenerational DMRs during gametogenesis. Male control and vinclozolin lineage F3 generation rats were used as a source of embryonic day 13 (E13) primordial germ cells, embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus vinclozolin lineage samples were determined for each developmental stage. The top 100 statistically significant DMRs for each stage were compared. The developmental origins of the caudal epididymal sperm DMRs were assessed. The chromosomal locations and genomic features of the different stage DMRs were investigated. In addition, the DMR associated genes were identified. Previous studies have demonstrated alterations in the DMRs of primordial germ cells (PGCs). Interestingly, the majority of the DMRs identified in the current study for the caudal sperm originated during the spermatogenic process in the testis. A cascade of epigenetic alterations initiated in the PGCs appears to be required to alter the epigenetic programming during spermatogenesis to modify the sperm epigenome involved in the transgenerational epigenetic inheritance phenomenon.
许多环境因素，从营养到有毒物质，都被证明可以促进疾病和表型变异的表观遗传跨代遗传。这需要改变生殖细胞系（精子或卵子）的表观基因组。此前，农业杀真菌剂表氯醇被发现可以促进精子差异 DNA 甲基化区域（DMRs）的跨代遗传，这些 DMRs 被称为表观突变，有助于介导这种表观遗传遗传。本研究旨在研究配子发生过程中跨代 DMR 的发育起源。雄性对照和表氯醇谱系 F3 代大鼠被用作胚胎第 13 天（E13）原始生殖细胞、胚胎第 16 天（E16）精原细胞、出生后第 10 天（P10）精原细胞、成年粗线期精母细胞、圆形精子、附睾头精子和尾部精子的来源。确定了每个发育阶段对照与表氯醇谱系样本之间的 DMR。比较了每个阶段前 100 个统计学上显著的 DMR。评估了尾部附睾精子 DMR 的发育起源。研究了不同阶段 DMR 的染色体位置和基因组特征。此外，还鉴定了与 DMR 相关的基因。以前的研究已经证明了原始生殖细胞（PGCs）中的 DMR 发生了改变。有趣的是，本研究中为尾部精子确定的大多数 DMR 起源于睾丸中的精子发生过程。似乎需要在 PGC 中启动一系列表观遗传改变，以改变精子发生过程中的表观遗传编程，从而改变参与跨代表观遗传遗传现象的精子表观基因组。
