Sodium fluoride disrupts testosterone biosynthesis by affecting the steroidogenic pathway in TM3 Leydig cells

Fluorine is an essential trace element to which humans and animals are exposed through water, food, air and products used for dental health. Numerous studies have reported the detrimental effects of fluoride on testicular function and fertility; however, the underlying mechanisms of testosterone biosynthesis remain unclear. In this study, Leydig cells, the primary cells responsible for the production and regulation of steroid hormones in the testis, were used to elicit effects of sodium fluoride on the steroidogenic pathway. Leydig cells were treated with 0, 0.1, 1, 10 and 100 mg/L sodium fluoride for 24 h, respectively. The result of the study showed that sodium fluoride significantly decreased cell viability and cell proliferation, increased cell cytotoxicity and decreased the amounts of testosterone and 3′,5′-cyclic adenosine monophosphate levels in a concentration-dependent manner. Also, these results indicated that NaF suppressed the expression of steroidogenic genes (steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase type I and 17β-hydroxy dehydrogenase type III) and proteins (luteinizing hormone receptor, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase), by changing the mRNA expression levels of the transcription factors (steroidogenic factor-1, GATA binding protein-4, nerve growth factor IB and nuclear receptor subfamily 0 group B member 1).