Paternal preconception phthalate exposure alters sperm methylome and embryonic programming

• DOI: 10.1016/j.envint.2021.106693
• Publication Date: 2021-06-10T12:03:28Z
• Authors: Oladele A. Oluway...; Chelsea Marcho; Haotian Wu; Emily Houle; Stephen A. Krawetz; Alexander Suvorov; Jesse Mager; J. Richard Pilsner
• Keywords: Differentially methylated regions

Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites males were associated with altered methylation blastocyst-stage embryo To corroborate this, we examined the effect of preconception exposure di(2-ethylhexyl) (DEHP) on genome-wide DNA gene expression profiles mice. Eight-week old C57BL/6J male mice exposed either a vehicle control, low, or high dose DEHP (2.5 25 mg/kg/weight, respectively) for 67 days (~2 spermatogenic cycles) mated unexposed females. Reduced representation bisulfite sequencing (RRBS) epididymal was performed gastrulation stage embryos collected RRBS transcriptome analyses both embryonic extra-embryonic lineages. Male resulted 704 differentially methylated regions (DMRs; q-value < 0.05; ≥10% change) sperm, 1,716 DMRs embryonic, 3,181 tissue. Of these, 29 overlapped between F1 tissues, half which concordant changes F0 generations. transcriptomes at E7.5 also by including developmental families such as Hox, Gata, Sox. Additionally, ontology expressed genes enrichment multiple processes development, pattern specification morphogenesis. These data indicate spermatogenesis adult may represent sensitive window alters methylome well developing embryo.