New approach for reproductive toxicity assessment: chromatoid bodies as a target for methylmercury and polychlorinated biphenyls in prepubertal male rats

Abstract

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.