Abstract
BackgroundEnvironmental impacts on a fetus can disrupt germ cell development leading to epimutations in mature germ cells. Paternal inheritance of adverse health effects through sperm epigenomes, including DNA methylomes, has been recognized in human and animal studies. However, the impacts of gestational exposure to a variety of environmental factors on the germ cell epigenomes are not fully investigated. Arsenic, a naturally occurring contaminant, is one of the most concerning environmental chemicals, that is causing serious health problems, including an increase in cancer, in highly contaminated areas worldwide. We previously showed that gestational arsenic exposure of pregnant C3H mice paternally induces hepatic tumor increase in the second generation (F2). In the present study, we have investigated the F1 sperm DNA methylomes genome-widely by one-base resolution analysis using a reduced representation bisulfite sequencing (RRBS) method.ResultsWe have clarified that gestational arsenic exposure increases hypomethylated cytosines in all the chromosomes and they are significantly overrepresented in the retrotransposon LINEs and LTRs, predominantly in the intergenic regions. Closer analyses of detailed annotated DNA sequences showed that hypomethylated cytosines are especially accumulated in the promoter regions of the active full-length L1MdA subfamily in LINEs, and 5′LTRs of the active IAPE subfamily in LTRs. This is the first report that has identified the specific positions of methylomes altered in the retrotransposon elements by environmental exposure, by genome-wide methylome analysis.ConclusionLowered DNA methylation potentially enhances L1MdA retrotransposition and cryptic promoter activity of 5′LTR for coding genes and non-coding RNAs. The present study has illuminated the environmental impacts on sperm DNA methylome establishment that can lead to augmented retrotransposon activities in germ cells and can cause harmful effects in the following generation.
Highlights
Environmental impacts on a fetus can disrupt germ cell development leading to epimutations in mature germ cells
The methylomes of F1 sperm were found to be less divergent with minor individual differences compared to those of normal livers and hepatic tumor tissues that were analyzed in our previous studies [18, 29] (Fig. 1a)
The average methylation levels of all CpG sites were 42.13 ± 0.04% in the control group and 41.90 ± 0.06% in the arsenic group. They were slightly lowered in autosomes and chromosome X and statistically significantly lowered in chrY of the arsenic group compared with the control group (Fig. 1b)
Summary
Environmental impacts on a fetus can disrupt germ cell development leading to epimutations in mature germ cells. Paternal inheritance of adverse health effects through sperm epigenomes, including DNA methylomes, has been recognized in human and animal studies. The impacts of gestational exposure to a variety of environmental factors on the germ cell epigenomes are not fully investigated. Nohara et al Epigenetics & Chromatin (2020) 13:53 animals Epigenomes, such as DNA methylomes, histone modifications and small RNAs of germ cells take pivotal roles in the inheritance, and paternal inheritance is exclusively attributed to the epigenomes of sperm [2, 3]. Gestational environmental exposure has been reported to affect epigenetic reprogramming leading to epimutations in mature germ cells and intergenerational and transgenerational outcomes [1, 2, 9]. The impacts of gestational exposure to a variety of environmental factors on the germ cell epigenomes are not fully clarified on molecular bases
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