Abnormal spermatogenesis following sodium fluoride exposure is associated with the downregulation of CREM and ACT in the mouse testis.

cAMP response element modulator (CREM) is involved in regulating gene expression in normal spermatogenesis. The transcriptional activity of CREM is partly regulated by activator of CREM in the testis (ACT). To investigate the effects of different concentrations of sodium fluoride (NaF) on the gene and protein expression of CREM and ACT in the mouse testis, sexually mature male Kunming mice were exposed to 50, 100, or 150 mg/L NaF in their drinking water for 90 days. NaF reduced the sperm count and viability and increased the percentage of malformed sperm in a dose-dependent manner. The mRNA expression of CREM and ACT was markedly downregulated in the NaF-treated groups. Furthermore, immunohistochemistry revealed that CREM and ACT proteins were decreased significantly in the 50, 100, and 150 mg/L NaF-treated groups compared to the control group. These findings indicate that the decreased gene and protein expression of CREM and ACT in the testis is associated with an impairment of reproductive functions by NaF.