It was reported that MCs accumulated mainly in liver and were known for their hepatotoxic effects. Moreover, MCs could also accumulate in heart, kidney and embryo, resulting in toxicity to those organs. Recently, several studies have demonstrated that MCs would exert negative effects on the male reproductive system and gonads are regarded as the second important target organs of MCs. It was reported that MCs could accumulate in testis and induce rat testis cell apoptosis, MCs could also induce morphological damages, cause significant decrease of sperm quality, and decline of serum hormones such as testosterone, follicular stimulating hormone and luteinizing hormone levels. However, molecular mechanisms underlying such reproductive toxicity of MCs are still unclear. A small subset of hypothalamic neurons expressing gonadotropin releasing hormone, the gonadotrope cells in anterior pituitary and the gonads form an integrated system hypothalamuspituitary-gonadal axis that is responsible for the adequate secretion of male hormones and normal spermatogenesis. The testes require stimulation by the pituitary gonadotropins such as luteinizing hormone and follicle-stimulating hormone, which are secreted in response to hypothalamic gonadotropin releasing hormone. The effect of LH and FSH on germ cell development is mediated by the androgen and FSH receptors that are present on Leydig and EX 527 citations Sertoli cells, respectively. Whereas FSH acts directly on the germinal epithelium and stimulates Sertoli cells to support spermatogenesis, LH promotes the Leydig cells to secrete testosterone which boosts sperm production and virilization and provides feedback to the hypothalamus and pituitary to regulate GnRH secretion. To date, few studies have been performed to evaluate the effects of MCs on HPG axis. The aim of the present study was to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. The results demonstrated that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes. To elucidate the associated possible mechanisms, the serum levels of testosterone, FSH and LH were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, GnRH and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. The exposure to MCs has been reported to induce reproductive toxicity to animals, however, the underlying mechanisms of reproductive toxicity of MCs are still unclear. In the present study, we demonstrated that exposure to different concentrations of MCLR significantly disturbed sperm production in the mice testis, which was associated with the suppression of GnRH expression that impaired the testosterone synthesis ability. Spermatogenesis is a complex process by which the spermatogonia mature gradually to spermatozoa through a series of events involving mitoses, meiosis and cellular differentiation.