The Enantioseletive Effect On Estrogen Metabolism By Four Pesticides

Chiral pesticides are used more and more popular. In this study, we employed typical chiral pesticides as model compounds, JEG-3 cell lines as in vitro model and assessed enantioselective disruption of these chiral pestisides towards the metabolic pathway of GnRH-mediated and estrogen derived from cholesterol synthesis. Besides, we desired to evaluate the potential risks of these compounds to maternal-fetal health. The results of real-time PCR revealed that these 4 typical chiral pesticides exhibited strong influence on these genes, including GnRH and its receptor, genes corresponding to enzymes of the steroidogenesis pathway and HLA-G. The enantioselective potential of endocrine disruption effect caused by the four chiral pestisides to these genes were as follows: R-(–)-o,p′-DDT >S-(+)-o,p′-DDT, S-(+)-AF > R-(–)-AF. The groups of 1R-cis-PM and 1S-trans-PM > 1S-cis-PM and 1R-trans-PM, (-)-Leptophos >(+)-Leptophos (p<0.05).The results of o,p′-DDT indicated that the effection of chiral contaminants were not merely on androgen steroid hormones or estrogen steroid hormones, but also showed disorder of endocrine regulation in vivo. Data of AF concerning on the steroidogenesis genes indicated that two enantiomers were not acted as a simple addition when mixed as equalmole. The endocrine disrupting effects of (-)-Leptophos was much stronger than (+)-Leptophos. To my best of my knowledge, our data firstly indicated that the enantioseletive effect of mammal and aquatic animal are different. o,p′-DDT and its two enantiomers exhibited significant up regulation on matrix metalloproteinases genes (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinases genes (TIMP 1, 3, 4). Besides, they also had the potential to promote invasiveness of breast cancer cell. What's more, our data showed that the disturbance of o,p'-DDT on invasiveness related genes were enantioselective. We hypothesis that the influence on cell invasiveness induced by o,p′-DDT and its two enantiomers may act both through classical ER and non-classical pathway.Conclusionlly, all factors should be taken into consideration about the health risk assessment of chiral pesticides such as cytotoxicity, reproduction disruption and oxidative stress. In particulary, it is imperative for assessing the enantioselective interference on internal steroidogenesis.