Investigation of the Effects of Xenoestrogens on the Protein Levels of the Estrogen Receptors

Abstract

There has been an increase in reports of male reproductive disorders that include male infertility and testicular cancer worldwide. It has been suggested that agents such as xenoestrogens could be responsible. Xenoestrogens are chemical compounds that mimic the action of estrogens by binding to the estrogen receptors (ERs). The response ofa testicular cell line to estrogenic pesticides was examined. The effect of estrogenic pesticides on the growth and protein levels of ERα and ERβ of mouse Sertoli cells was investigated. Pyrethroids are widely used insecticides due to their insecticidal potency and low mammalian toxicity. In this study, the estrogenicity ofpyrethroid chemicals were tested using the yeast estrogen screen (YES) assay. The toxic effects of the pyrethroid compounds cypermethrin, 3-(4-hydroxy-phenoxy)benzyl alcohol (metabolite of permethrin), and the commercial product (Ripcord Plus) were evaluated. The Sertoli cells were exposed to pyrethroids at concentrations of 0.36 nM and 36 µM (cypermethrin and Ripcord Plus), and 0.69 nM and 69 µM (metabolite) for 100 h. The expression of the ERs was analysed through the use of Enzyme Linked ImmunoSorbent Assay (ELISA) experiments. The most toxic pyrethroid was the metabolite, followed by Ripcord Plus then cypermethrin. Overall the exposure of the cells to cypermethrin (36 µM), Ripcord Plus (36 µM) and the metabolite (69 µM) caused a significant decrease (p<0.05) in ERα levels. In the cultures exposed to the metabolite (69 µM), there was also a significant increase in ERβ levels. There appears to be a relation between cell toxicity and an increase in ERβ levels, which supports the theory that ERβ promotes apoptosis. Pyrethroids are rapidly excreted from the body, and it is unknown if there is accumulation in the male testes. Male fertility could be affected through molecular mechanisms involving the ERs, should cells in the male testes be exposed to these pyrethroids at physiologically relevant concentrations.