Disruption of androgen receptor signaling by chlorpyrifos (CPF) and its environmental degradation products: a structural insight.

Androgen-disruptors are chemicals that interfere with the biosynthesis, metabolism or function of endogenous androgens affecting normal male reproductive development and health. Several epidemiological studies have indicated a link between exposure to androgen disrupting chemicals with reduced sperm counts and increased infertility. The actions of androgens within target cells are transduced by the androgen receptors (ARs). Chlorpyrifos (CPF), a chlorinated organophosphorus pesticide, is known to cause impairment in both male and female reproductive systems. Recent publications have shown molecular interactions of CPF and its environmental degradation products with human progesterone receptor and human estrogen receptor. Exposure to CPF causes a marked reduction in sperm counts with lowering in serum testosterone level, which suggests possible molecular interaction of CPF with AR. The investigation to reveal the possibility and the extent of binding of CPF and some of its degradation products (chlorpyrifos-oxon [CPYO], desethyl chlorpyrifos [DEC], trichloromethoxypyridine [TMP] and trichloropyridinol [TCP]) with AR using molecular docking simulation are reported. The findings of the present docking, binding energy and molecular dynamics studies reveal that CPF and its degradation products may bind to ARs and act as a potent androgen disruptor.Communicated by Ramaswamy H. Sarma.