RESUMO
Exposure of Sprague-Dawley (SD) rats to acrylamide (AA) or di-butyl-phthalate (DBP) from the 12th gestational day to the 16th postnatal week (PNW) has been shown to reduce the effectiveness of orchiopexy in recovering the testicular alterations associated with experimental cryptorchidism established at weaning. Herein, we provide information about the long-term effects of AA or DBP on the testes of cryptorchid/orchiopexic rats. Male offspring exposed in utero to 10 mg/kg/day AA or 500 mg/kg/day DBP underwent bilateral surgical cryptorchidism at the 3rd PNW and orchiopexy at the 6th week, with continuous exposure to the chemicals through diet until the 58th week. Regardless of the test chemical, there were severe qualitative/quantitative alterations in the seminiferous tubules and increased numbers of Leydig cells. There was an increase and decrease in the number of tubules with c-Kit- and placental alkaline phosphatase-labeled germ cells, respectively, as compared to those in the control group, suggesting an imbalance between apoptosis and cell proliferation processes. The histological scores of the testicular lesions at the end of this one-year study were higher than those in the previous 16-week study, indicating that exposure of rats to the toxicants AA or DBP enhanced the testicular alterations induced by the chemicals beginning at the intra-uterine life, and impaired the effectiveness of orchiopexy in restoring the testes to normal morphology. Although the present experimental protocol does not completely replicate the natural human undescended testes, our findings may contribute to understanding the alterations occurring in cryptorchid/orchiopexic testes potentially exposed to exogenous chemicals for extended periods.
RESUMO
Arsenic is a toxic metalloid widely present in the earth's crust, and is a proven human carcinogen. Chronic arsenic exposure mainly through drinking water causes skin, lung, and urinary bladder cancers, and is associated with liver, prostate, and kidney cancers, cardiovascular and neurological disorders, and diabetes. Several modes of action have been suggested in arsenic carcinogenesis. However, the molecular etiology of arsenic-induced cancer remains unclear. Recent evidence clearly indicates that gene expression modifications induced by arsenic may involve epigenetic alterations, including miRNA dysregulation. Many miRNAs have been implicated in different human cancers as a consequence of losses and or gains of miRNA function that contribute to cancer development. Progress in identifying miRNA dysregulation induced by arsenic has been made using different approaches and models. The present review discusses the recent data regarding dysregulated expression of miRNA in arsenic-induced malignant transformation in vitro, gaps in current understanding and deficiencies in current models for arsenic-induced carcinogenesis, and future directions of research that would improve our knowledge regarding the mechanisms involved in arsenic-induced carcinogenesis.
