DNA methylation changes of apoptotic genes in organogenesis stage of mice embryos by maternal chlorpyrifos induction

Abstract

The continued use of pesticides is one of the requirements of modern agriculture. Investigations have shown that pesticides can alter gene methylation and expression and subsequently may lead to abortion or birth of embryos with teratogenic disorders. In present study, 30 female NMRI mouse were divided in three experimental groups which in the CPF group, intraperitoneal chlorpyrifos was injected, in the sham group, DMSO was injected, and the control group without injection. The mice were mated and utinized 10 days' post gestation. The number of embryos in each fertilized female, maternal weight, and liver fibrosis was evaluated. The apoptosis pathway genes (caspase3, caspase9) and protein expressions (pro-caspase3, caspase3) of the embryos were evaluated with qRT-PCR and western blot, respectively. The DNA methylation of caspase3 and caspase9 were also assessed. The number of embryos and obtained maternal weight from the CPF group was significantly lower than other two groups. The mRNA expression of Caspase3 and Caspase9 were significantly higher in the CPF group. The protein expression evaluation confirmed the results achieved at the mRNA level. The percentage of Caspase9 DNA methylation in embryos collected from the CPF group was higher compared to the others. It can be considered that consumption of chlorpyrifos toxin can alter the DNA methylation and increase the expression of apoptotic genes. Therefore, continuous use of chlopyrifos may affect pregnancy by increasing the apoptosis pathway in the developing embryos which may lead to abortion or teratogenic disorders in newborn infants.