Arch Toxicol (2010) 84:53–61 DOI 10.1007/s00204-009-0479-y 123 ORGAN TOXICITY AND MECHANISMS Cypermethrin exposure during puberty disrupts testosterone synthesis via downregulating StAR in mouse testes Hua Wang · Qun Wang · Xian-Feng Zhao · Ping Liu · Xiu-Hong Meng · Tao Yu · Yan-Li Ji · Heng Zhang · Cheng Zhang · Ying Zhang · De-Xiang Xu Received: 15 July 2009 / Accepted: 8 October 2009 / Published online: 28 October 2009  Springer-Verlag 2009 Abstract Cypermethrin is a widely used synthetic pyre- throid insecticide. Previous studies showed that cypermeth- rin signiWcantly decreased the fertility and reduced the number of implantation sites and viable fetuses in females impregnated by males exposed to cypermethrin. As yet, lit- tle is known about the mechanism of cypermethrin-induced reproductive toxicity. In the present study, we investigated the eVects of cypermethrin exposure during puberty on ste- roidogenesis in mice. Young male mice were administered with cypermethrin (25 mg/kg) by gavage daily from post- natal day (PND) 35 to PND70. Results showed that the level of serum and testicular testosterone (T) was markedly decreased in cypermethrin-treated mice. Additional experi- ment showed that cypermethrin exposure during puberty markedly downregulated mRNA level of steroidogenic acute regulatory protein (StAR) in testes. Correspondingly, protein level of testicular StAR was signiWcantly decreased in cypermethrin-treated mice. Cypermethrin exposure dur- ing puberty did not aVect the number of Leydig cells in tes- tes. Although cypermethrin exposure during puberty did not aVect the weight of testes and epididymides, the number of sperm in the cauda epididymides was signiWcantly decreased in cypermethrin-treated mice. Taken together, these results indicate that cypermethrin exposure during puberty signiWcantly disrupts T synthesis via downregu- lating the expression of testicular StAR. The decreased T synthesis might be associated with cypermethrin-induced impairment in spermatogenesis in mice. Keywords Cypermethrin · Pyrethroid · Testes · Steroidogenesis · Testosterone · Steroidogenic acute regulatory protein (StAR) Introduction Cypermethrin is a synthetic pyrethroid insecticide, which has been commonly used to control noxious insects in agri- culture, forestry, horticulture, public health, and so forth. Cypermethrin is a well-known neurotoxicant (Dési et al. 1986; McDaniel and Moser 1993; Wolansky and Harrill 2008). In vivo studies showed that cypermethrin exposure resulted in alterations of motor function and impairments of neurobehaviors in rodents (McDaniel and Moser 1993; Wolansky et al. 2006, 2008). Like other synthetic pyre- throid insecticides, cypermethrin is also a mutagen (Bhunya and Pati 1988; Surrallés et al. 1995). An earlier study showed that a single dose of cypermethrin signiWcantly increased the frequency of sister chromatid exchange in mouse bone marrow cells (Chauhan et al. 1997). A recent study found that cypermethrin increased the incidence of sister chromatid exchange, chromosomal aberrations, and micronuclei in human peripheral lymphocytes (Kocaman and Topaktas 2009). Recently, pyrethroids have been found to have poten- tially adverse eVects on male reproduction. An earlier study showed that fenvalerate exposure to adult rats by inhalation obviously induced the decrease in testicular weight, epidid- ymal sperm counts, and sperm motility (Mani et al. 2002). In addition, the expression of testicular 17-hydroxysteroid dehydrogenase (17-HSD), a testosterone (T) biosynthetic Hua Wang, Qun Wang and Xian-Feng Zhao are contributed equally to this work. H. Wang · Q. Wang · X.-F. Zhao · P. Liu · X.-H. Meng · T. Yu · Y.-L. Ji · H. Zhang · C. Zhang · Y. Zhang · D.-X. Xu (&) Department of Toxicology, Anhui Medical University, Hefei 230032, China e-mail: xudex@mail.hf.ah.cn