Transgenerational Effect of a Mixture of Pyrethroids in the Testis of Rats: A Transcriptome and Epigenome Analyses

Pyrethroids exert toxic effects on multiple organ systems, including the male reproductive tract. We previously demonstrated the toxicity of a mixture of pyrethroids in rats when administered at doses equivalent to human exposure. It is possible that the toxic effects observed in the exposed generations may be transmitted to the next generations. In this study, the transgenerational toxicity on the transcriptome and epigenome was evaluated in the testes of rats exposed to a mixture of pyrethroids and in the testes of rats obtained from subsequent generations (up to F3 generation). Exposure to a mixture of pyrethroids resulted in perturbations in the transcriptome in the course of the treatment and after three generations. Epigenome analyses revealed that 143 genes were differentially methylated in in the testes of pyrethroid treated rats (F0 generation), while it was 149, 142 and 116 in the testes of F1, F2 and F3 generation rats respectively. Interestingly, some of the differentially methylated genes/loci were related to male reproductive function in each of the generations. Eleven genes/loci displayed similar altered methylation status across the four generations, of which LOC100910657 (sperm motility kinase Y-like), LOC685793 (serine/threonine kinase) and Adam 28, are predicted to be strongly associated with male reproductive function, especially sperm function. Results of this study demonstrate that the toxicological effects caused by a mixture of pyrethroids can be transmitted to further generations even though the offspring were never exposed to the toxicants. The findings from this study reflect human settings and justifies the probable transgenerational effects due to pyrethroid exposure through food consumption.