Microcystin-leucine arginine induced the apoptosis of GnRH neurons by activating the endoplasmic reticulum stress resulting in a decrease of serum testosterone level in mice.

Haibo Jin, Jiwei Hou, Xiannan Meng, Tan Ma, Bo Wang, Zhenyu Liu, Xiaoxuan Sha, Jie Ding, Xiaodong Han

Ecotoxicology and environmental safety 2021 Jan 15

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Microcystin-leucine arginine (MC-LR) is a kind of toxin produced by cyanobacterial, resulting in decrease of testosterone levels in serum and leading to impaired spermatogenesis. Gonadotropin-releasing hormone (GnRH) neurons play crucial roles in the regulation of testosterone release. Meanwhile, it has been demonstrated that MC-LR is capable of entering the GnRH neurons and inducing apoptosis. Nevertheless, the molecular mechanism of MC-LR induced apoptosis of GnRH neurons remains elusive. In present study, we found that MC-LR inhibited the cell viability of GT1-7 cells. In addition, we discovered apoptosis of GnRH neurons and GT1-7 cells treated with MC-LR. And increased intracellular ROS production and the release of intracellular Ca2+ were all observed following exposure to MC-LR. Furthermore, we also found the endoplasmic reticulum stress (ERs) and autophagy were activated by MC-LR. Additionally, pretreatment of the ERs inhibitor (4-Phenyl butyric acid) reduced the apoptotic rate of GT1-7 cells comparing with MC-LR exposure alone. Comparing with MC-LR treatment alone, apoptotic cell death was increased by pretreatment of GT1-7 cells with an autophagy inhibitor (3-methyladenine). Together, our data implicated that the treatment of MC-LR induced the apoptosis of GnRH neurons by activating the ERs resulting in a decrease of serum testosterone level in mice. Autophagy is a protective cellular process which was activated by ER stress and thus protected cells from apoptosis upon MC-LR exposure. Copyright © 2020. Published by Elsevier Inc.

Citation

Haibo Jin, Jiwei Hou, Xiannan Meng, Tan Ma, Bo Wang, Zhenyu Liu, Xiaoxuan Sha, Jie Ding, Xiaodong Han. Microcystin-leucine arginine induced the apoptosis of GnRH neurons by activating the endoplasmic reticulum stress resulting in a decrease of serum testosterone level in mice. Ecotoxicology and environmental safety. 2021 Jan 15;208:111748