Abstract
BackgroundMicrocystins 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.MethodsAdult 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.ConclusionsMC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.
Highlights
Cyanobacterial blooms and the production of secondary metabolites cyanotoxins represent a serious public health hazard to humans and animals worldwide since the cyanotoxins can be accumulated in aquatic organisms and transferred to higher trophic levels [1,2]
Effect of Microcystins LR (MC-LR) on the Sperm production To determine whether MC-LR administration affects the spermatogenesis of mice, mice were treated with MC-LR at various concentrations (0, 3.75, 7.50, 15.00 and 30.00 mg/kg body weight per day), at the indicated time point, the epididymides were removed and minced to release sperm into the medium. the sperm quantity was measured using a hemacytometer
At day 1, there was no difference of the epididymal sperm production between various concentrations of MC-LR and the control group ((0 mg/kg/day MC-LR)
Summary
Cyanobacterial blooms and the production of secondary metabolites cyanotoxins represent a serious public health hazard to humans and animals worldwide since the cyanotoxins can be accumulated in aquatic organisms and transferred to higher trophic levels [1,2]. One of the most frequently studied cyanotoxins is the cyclic heptapeptide hepatotoxins called microcystins (MCs) due to their wide distribution and high toxicity. More than 80 analogues of MCs have been identified, with microcystin-LR (MC-LR) being the most common and toxic [3]. It was reported that MCs accumulated mainly in liver and were known for their hepatotoxic effects [7]. MCs could accumulate in heart, kidney and embryo, resulting in toxicity to those organs [8]. 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. This study aimed to investigate the MC-LRinduced toxicity in the reproductive system of mouse and focus on the HPG axis
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