The mechanisms of prenatal cadmium (Cd) exposure cause adverse effect transmission to future generations that remain unclear. In this study, pregnant SD rats were orally dosed with Cd (0, 0.5, 2.0, and 8.0 mg/kg/day) from gestation day 1 until birth. F1 female rats were mated with untreated males for F2 generation. In both generations, after prenatal Cd exposure, histopathological examinations showed testicular development disorder. A significant decrease in serum testosterone (T) was observed in the F1 rats, but a significant increase in serum T was observed in the F2 rats. Moreover, both the F1 and F2 rats had different patterns of mRNA and protein expression for testicular steroidogenic factor 1 (SF-1) and steroidogenic enzymes at postnatal days (PNDs) 21 and 56. We also found that rno-miR-328a-5 and rno-miR-10b-5p significantly changed and TargetScan software showed that both of these microRNAs targeted SF-1 and steroidogenic acute regulatory (StAR), respectively. Overall, the results indicate that prenatal Cd exposure causes male reproductive problems in a multigenerational manner. In addition, SF-1 signaling was disrupted and the expressions of microRNAs were affected, which may be an important target for Cd-induced reproductive toxicity in offspring.
Keywords: Cadmium; F1; F2; MicroRNAs; Steroidogenic factor 1; Testosterone.
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