Effects of low doses of carbendazim or iprodione either separately or in mixture on the pubertal rat seminiferous epithelium: An ex vivo study

Toxicol In Vitro. 2017 Dec;45(Pt 3):366-373. doi: 10.1016/j.tiv.2017.05.022. Epub 2017 May 30.

Abstract

It has been shown that non-cytotoxic doses of Carbendazim (CBZ), a broad-spectrum benzimidazole fungicide, possess endocrine-disrupting (androgen-like) actions, ex vivo, on the pubertal rat seminiferous epithelium. Iprodione (IPR), a dicarboximide fungicide, is also known to be an endocrine-disrupter (anti-androgen). The effect of a mixture of these two pesticides was investigated in the validated rat seminiferous tubule culture model. Cultures were performed in the absence or presence of CBZ 50nM or IPR 50nM either alone or in mixture (Mix), over a 3-week period. Mix exerted a dramatic effect on two proteins (Connexin 43 and Claudin-11) of the blood-testis barrier and possessed similar effects to IPR on some germ cell populations. The presence of IPR together with CBZ (Mix) cancelled the effect of CBZ on the increase of the androgen-dependent TP1 and TP2 mRNAs and on the decrease of ERα, ERβ mRNAs. Nevertheless, CBZ alone or IPR alone or Mix induced toxicity on spermatogenesis resulting in a decrease of round spermatids (the precursors of spermatozoa). These results strongly suggest that, even at these low concentrations, the effects of IPR and of CBZ are not solely dependent on their respective anti-androgenic and androgen-like effects and should involve several mechanisms of action.

Keywords: Carbendazim; Iprodione; Low doses; Mixture; Spermatogenesis; ex vivo study.

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / toxicity
  • Animals
  • Benzimidazoles / toxicity*
  • Blood-Testis Barrier / drug effects
  • Carbamates / toxicity*
  • Cells, Cultured
  • Claudins / biosynthesis
  • Claudins / genetics
  • Connexin 43 / biosynthesis
  • Connexin 43 / genetics
  • Endocrine Disruptors / toxicity*
  • Fungicides, Industrial / toxicity*
  • Gene Expression Regulation / drug effects
  • Hydantoins / toxicity*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Seminiferous Epithelium / drug effects*
  • Sexual Maturation
  • Spermatocytes / drug effects
  • Spermatogenesis / drug effects

Substances

  • Benzimidazoles
  • Carbamates
  • Claudins
  • Cldn11 protein, rat
  • Connexin 43
  • Endocrine Disruptors
  • Fungicides, Industrial
  • Gja1 protein, rat
  • Hydantoins
  • Aminoimidazole Carboxamide
  • carbendazim
  • iprodione