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      Effect of Cyanotoxins on the Hypothalamic–Pituitary–Gonadal Axis in Male Adult Mouse

      1 , 2 , 3 , *

      PLoS ONE

      Public Library of Science

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          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.


          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.


          MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

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          Most cited references 34

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          Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants.

          The cyclic heptapeptide, microcystin-LR, inhibits protein phosphatases 1 (PP1) and 2A (PP2A) with Ki values below 0.1 nM. Protein phosphatase 2B is inhibited 1000-fold less potently, while six other phosphatases and eight protein kinases tested are unaffected. These results are strikingly similar to those obtained with the tumour promoter okadaic acid. We establish that okadaic acid prevents the binding of microcystin-LR to PP2A, and that protein inhibitors 1 and 2 prevent the binding of microcystin-LR to PP1. We discuss the possibility that inhibition of PP1 and PP2A accounts for the extreme toxicity of microcystin-LR, and indicate its potential value in the detection and analysis of protein kinases and phosphatases.
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            The central role of Sertoli cells in spermatogenesis.

             M D Griswold (1998)
            Sertoli cells are the somatic cells of the testis that are essential for testis formation and spermatogenesis. Sertoli cells facilitate the progression of germ cells to spermatozoa via direct contact and by controlling the environment milieu within the seminiferous tubules. The regulation of spermatogenesis by FSH and testosterone occurs by the action of these hormones on the Sertoli cells. While the action of testosterone is necessary for spermatogenesis, the action of FSH minimally serves to promote spermatogenic output by increasing the number of Sertoli cells. Copyright 1998 Academic Press.
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              Ecotoxicological effects of selected cyanobacterial secondary metabolites: a short review.

              Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Many of them are able to produce a wide range of toxic secondary metabolites. These cyanobacterial toxins can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production of secondary metabolites and endotoxins, which could be toxic to animals and plants. Many of the freshwater cyanobacterial blooms include species of the toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ in mechanisms of uptake, affected organs, and molecular mode of action. In this review, the main focus is the aquatic environment and the effects of these toxins to the organisms living there. Some basic toxic mechanisms will be discussed in comparison to the mammalian system.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                6 November 2014
                : 9
                : 11
                [1 ]Department of Endocrinology, the Affiliated Drum Tower Hospital, Nanjing Medical University, Nanjing, China
                [2 ]Department of Respiratory Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, China
                [3 ]Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China
                Clermont Université, France
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: XX. Performed the experiments: XX AZ. Analyzed the data: XX HX. Contributed reagents/materials/analysis tools: XX HX AZ. Wrote the paper: XX HX. Contribution type: XX HX AZ.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 9
                This project was funded by the National Natural Science Foundation of China under the grant 81200587. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Biology and Life Sciences
                Chemical Ecology
                Toxin Binding
                Earth Sciences
                Marine and Aquatic Sciences
                Aquatic Environments
                Freshwater Environments
                Ecology and Environmental Sciences



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