Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.
BACKGROUND
Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis.


METHODS
Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro.


RESULTS
MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice.


CONCLUSIONS
MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.
Department of Endocrinology, the Affiliated Drum Tower Hospital, Nanjing Medical University, Nanjing, China.
Xiaolu
X
Xiong
Department of Respiratory Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Anyuan
A
Zhong
Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
Huajun
H
Xu
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007985:Leydig Cells / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008387:Marine Toxins; D051379:Mice; D008810:Mice, Inbred C57BL; D052998:Microcystins / Q000008:administration & dosage*; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D008387:Marine Toxins; D052998:Microcystins; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C057862:cyanoginosin LR