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

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

doi:10.1016/j.ecoenv.2020.111748

Cited by 13 publications

(6 citation statements)

References 39 publications

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“…MC-LR lowered the T, LH, and FSH serum levels and decreased testis weight and sperm concentration in rats after 28 days of exposure [71], and, similarly, decreased serum T concentrations, impaired sperm quality, and led to testicular injury in mice chronically exposed to low-dose exposures of MC-LR (3-6 months) [83]. Numerous studies have reported a decrease in T levels after exposure to MC-LR in mammals [46,71,72,[75][76][77][81][82][83][84]. However, the response in the case of FSH and LH levels or the expression of FSH and LH genes after toxin exposure was more variable: sometimes it decreased [71,72]; at times it increased [46,80,83,84]; and even initial increases were followed by decreases in mice exposed to MC-LR [45,46].…”

Section: Androgenic/antiandrogenic Effects Of Mcs and Consequences On...mentioning

confidence: 90%

“…The androgenic/antiandrogenic effects of MCs and their potential influence on the reproduction of males are shown in Table 2. Most of the studies were carried out in vivo on mammals, while in vitro studies were less frequent, highlighting the research performed with a double strategy, using in vivo and parallel in vitro assays [45,46,[71][72][73][74][75][76][77]. Moreover, only a few studies have been performed using fish [78] and, occasionally, the effects of MC-LR have been explored in amphibians [79,80] and crustaceans [81,82].…”

Section: Androgenic/antiandrogenic Effects Of Mcs and Consequences On...mentioning

confidence: 99%

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Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review

Casas-Rodríguez

Cameán

Jos

2022

Toxins

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Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of ED on humans, mammals, and aquatic organisms, this work aimed to review the state-of-the-art regarding the toxic effects of MCs and CYN at this level. It has been evidenced that MCs have been more extensively investigated than CYN. Reported results are contradictory, with the presence or absence of effects, but experimental conditions also vary to a great extent. In general, both toxins have shown ED activity mediated by very different mechanisms, such as estrogenic responses via a binding estrogen receptor (ER), pathological changes in several organs and cells (testis, ovarian cells), and a decreased gonad-somatic index. Moreover, toxic effects mediated by reactive oxygen species (ROS), changes in transcriptional responses on several endocrine axes and steroidogenesis-related genes, and changes in hormone levels have also been reported. Further research is required in a risk assessment frame because official protocols for assessment of endocrine disrupters have not been used. Moreover, the use of advanced techniques would aid in deciphering cyanotoxins dose-response relationships in relation to their ED potential.

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Section: Androgenic/antiandrogenic Effects Of Mcs and Consequences On...mentioning

confidence: 90%

Section: Androgenic/antiandrogenic Effects Of Mcs and Consequences On...mentioning

confidence: 99%

Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review

Casas-Rodríguez

Cameán

Jos

2022

Toxins

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“…The mechanisms of MCs neurotoxicity were reviewed by different researchers [ 282 , 283 ]. Thus, MC-LR can induce apoptosis and atrophy of gonadotropin-releasing hormone (GnRH) neurons in rats’ hypothalamus [ 284 , 285 ]. Although the molecular mechanism of MC-LR- induced apoptosis remains elusive, growing evidence supports that MCs and other cyanobacterial toxins, such as cylindrospermopsin, act as endocrine disruptors [ 286 , 287 ].…”

Section: Mechanisms Of Brain Toxicitymentioning

confidence: 99%

Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases

Nugumanova

Ponomarev

Askarova

et al. 2023

Toxins

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Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. Major mechanisms related to the neurotoxicity of cyanobacteria compounds include (1) blocking of key proteins and channels; (2) inhibition of essential enzymes in mammalian cells such as protein phosphatases and phosphoprotein phosphatases as well as new molecular targets such as toll-like receptors 4 and 8. One of the widely discussed implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids. Recent research provides evidence that non-proteinogenic amino acid BMAA produced by cyanobacteria have multiple effects on translation process and bypasses the proof-reading ability of the aminoacyl-tRNA-synthetase. Aberrant proteins generated by non-canonical translation may be a factor in neuronal death and neurodegeneration. We hypothesize that the production of cyanopeptides and non-canonical amino acids is a more general mechanism, leading to mistranslation, affecting protein homeostasis, and targeting mitochondria in eukaryotic cells. It can be evolutionarily ancient and initially developed to control phytoplankton communities during algal blooms. Outcompeting gut symbiotic microorganisms may lead to dysbiosis, increased gut permeability, a shift in blood-brain-barrier functionality, and eventually, mitochondrial dysfunction in high-energy demanding neurons. A better understanding of the interaction between cyanopeptides metabolism and the nervous system will be crucial to target or to prevent neurodegenerative diseases.

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“…Although postnatal GnRH neurons have previously been suggested to undergo apoptotic death following exposure to toxins ( 71 , 72 ), death as a cause of postnatal GnRH neuronal loss has never been documented in the whole organism. More indirect evidence suggests postnatal GnRH neurons may, more frequently, undergo de-differentiation and completely lose their ability to produce GnRH.…”

Section: The Maintenance Of Postnatal Gnrh Neuronsmentioning

confidence: 99%

The initiation and maintenance of gonadotropin-releasing hormone neuron identity in congenital hypogonadotropic hypogonadism

Chung

Tsai

2023

Front. Endocrinol.

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Neurons that secrete gonadotropin-releasing hormone (GnRH) drive vertebrate reproduction. Genetic lesions that disrupt these neurons in humans lead to congenital hypogonadotropic hypogonadism (CHH) and reproductive failure. Studies on CHH have largely focused on the disruption of prenatal GnRH neuronal migration and postnatal GnRH secretory activity. However, recent evidence suggests a need to also focus on how GnRH neurons initiate and maintain their identity during prenatal and postnatal periods. This review will provide a brief overview of what is known about these processes and several gaps in our knowledge, with an emphasis on how disruption of GnRH neuronal identity can lead to CHH phenotypes.

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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

Cited by 13 publications

References 39 publications

Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review

Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review

Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases

The initiation and maintenance of gonadotropin-releasing hormone neuron identity in congenital hypogonadotropic hypogonadism

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