The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome—a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men
Ariane Lismer, Xiaojian Shao, Marie-Charlotte Dumargne, Christine Lafleur, Romain Lambrot, Donovan Chan, Gunnar Toft, Jens Peter Bonde, Amanda J MacFarlane, Riana Bornman, Natalie Aneck-Hahn, Sean M. Patrick, Janice M. Bailey, C. de Jager, Vanessa Dumeaux, Jacquetta M. Trasler, Sarah Kimmins
Abstract
BACKGROUND: DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. OBJECTIVES: DDE serum levels between geographically diverse populations. METHODS: -DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. RESULTS: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. DISCUSSION: DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.