Androgen Receptor Plays a Vital Role in Benomyl- or Carbendazim-Induced Reproductive and Developmental Toxicity and Endocrine-Disrupting Activity in Rats

Abstract

Benomyl and its metabolite carbendazim were reported to induce reproductive and developmental toxicity and endocrine-disrupting activity in rats. The exactly underlying mechanism of reproductive and developmental toxicity and endocrine-disrupting activity still remain unclear. Based on our unpublished data it showed that the antiandrogen flutamide can completely recover the reproductive and developmental toxicity including embryolethality induced by benomyl and carbendazim in rats. This manuscript aimed to review and generalize the results based on our previous reports. Androgen receptor might play an important role in benomyl-and carbendazim-induced reproductive and developmental toxicity and endocrine-disrupting activity. The evidences were (1) andro-gen-and androgen receptor-dependent mechanisms are possibly involved in carben-dazim-induced toxicity; (2) carbendazim exposure in utero displays a transient and weak androgenic effect and reduces flutamide antiandrogenicity in male rats; (3) antagonistic effect of flutamide on the carbendazim-androgenic effect on mRNA and protein levels; (4) benomyl and carbendazim exhibit an androgenic effect, leading to increase weight of ventral prostate and seminal vesicles and uterine fluid retention in young adult rats. The molecular underlying mechanism of reproductive and developmental toxicity and endocrine-disrupting activity induced by benomyl and carbendazim through androgen receptor need to be further investigated.