Changes in testicular function proteins and sperm acrosome status in rats treated with valproic acid

Abstract

Valproic acid (VPA), an anti-epileptic drug, reduces testosterone levels and sperm quality. However, the degree to which testosterone levels and sperm quality are decreased under VPA treatment needs to be clarified. The aim of the present study was to investigate the testicular proteins involved in testosterone synthesis and spermatogenesis, histopathology and sperm acrosome status in VPA-treated rats. Adult rats were divided into control and experimental groups (n = 8 in each). Rats in the experimental group were treated with 500 mg kg–1, i.p., VPA for 10 consecutive days. Expression of Ki-67, tyrosine phosphorylated proteins and testicular steroidogenic proteins was examined. As expected, VPA-treated rats exhibited adverse changes in almost all reproductive parameters, particularly an increase in precocious acrosome reactions, compared with the control group. In addition, fibrosis of the tunica albuginea and tubule basement membrane was observed in testes from VPA-treated rats. Moreover, the expression of testicular Ki-67, cholesterol side-chain cleavage enzyme (P450scc) and phosphorylated proteins (41, 51 and 83 kDa) was decreased significantly in VPA-treated rats compared with control. In contrast, the expression of steroidogenic acute regulatory proteins in the VPA-treated group was significantly higher than in the control group. In conclusion, VPA treatment changes the expression of testicular proteins responsible for spermatogenesis and testosterone production, resulting in male infertility.