Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

Wang, Xueting; Ding, Jie; Zou, Xiang; Jiang, Pengju; Du, Jing; Han, Xiaodong

doi:10.1016/j.toxicon.2016.10.011

Cited by 19 publications

(10 citation statements)

References 51 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: 89%

“…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%

“…In vivo, MC-LR affects the serum levels of hormones and their expression by affecting the HPG [45,46]. Through this axis, gonadotropin-releasing hormones (GnRHs) released from the hypothalamus stimulate the secretion of gonadotropin hormones (GtHs), including follicle-stimulating hormones (FSH) and luteinizing hormones (LH), by the pituitary.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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: 89%

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

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Casas-Rodríguez

Cameán

Jos

2022

Toxins

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“…Histological examination showed that the testis atrophied and the structure of seminiferous tubules was damaged in the MC group ( 18 ). The main function of Leydig cells is to produce androgen, which is necessary for spermatogenesis, maturation and the maintenance of libido ( 20 ). A decrease in testosterone may reflect damage of interstitial cells caused by MC-LR exposure.…”

Section: Discussionmentioning

confidence: 99%

Water Blooms—A Potential Threat to Male Reproduction: Clues From Aquatics and Rodents

Liu

2022

Front. Endocrinol.

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Toxic cyanobacteria blooms are a potential threat to global aquatic ecosystems and human health. Microcystin-leucine-arginine (MC-LR) is the most toxic variant of microcystins (MCs), and exposure to MCs can damage the male reproductive system. Two electronic databases were searched for controlled studies of rodents and fishes published before September 2020. Effect sizes were calculated for eight main reproductive parameters, including sperm count, sperm motility, sperm morphology, serum testosterone, testis weight, serum follicle stimulating hormone (FSH), serum luteinising hormone (LH) and serum estradiol. Nine meta-analyses of individual parameters were conducted using R version 4.0.2. Fifteen studies were included in the meta-analysis. In the studies of rodents, exposure to MC-LR by intraperitoneal injection or intragastric administration yielded statistically significant effects on sperm count (standardised mean difference (SMD) = -1.7426 (95% CI: -2.2098 to -1.2754)), abnormal sperm rate (SMD = 1.6714 (95% CI: 0.9702 to 2.3726)), sper5% CI: -3.9811 to -1.7834)), testis weight (SMD = -2.8822 (95% CI: -3.9811 to -1.7834)) and serum FSH (SMD = 0.4707 (95% CI: 0.0659 to 0.8756) changes in serum testosterone (SMD = 0.5521 (95% CI: 0.1652; 0.9391)) and estradiol (SMD = 0.6398 (95% CI: 0.1896 to 1.0900)) concentrations are considered to be statistically significant. Dose–response analysis reflected the dynamic changes of male reproductive function caused by MC. Short-term exposure to MC-LR can affect the function of the male reproductive system in rodents and fish. Elevated dosage or extended exposure time may worsen the damage. Human-related research on MC-LR exposure is very necessary to protect health and the water environment.

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“…MC exposure protocols frequently use intraperitoneal (i.p.) injection or oral gavage administration in order to control for measured dosing and delivery [ 12 , 25 , 29 , 30 , 31 ]. However, these two standard practice exposures for MC-LR toxicity produce drastically different lethal dose (LD50) estimates, with i.p.…”

Section: Introductionmentioning

confidence: 99%

Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice

Mrdjen

Morse

Ruch

et al. 2018

Toxins

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Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, and death in extreme circumstances. The goal of this study was to provide an accurate and comprehensive description of MC-LRs impacts on liver pathology, clinical chemistry, and gap junction intercellular communication (GJIC) in CD-1 male and female mice. Mice were exposed to 0, 3000, and 5000/4000 µg/kg/day MC-LR, daily for 7 days, and were necropsied on Day 8. Blood samples for clinical chemistry analysis were processed to serum, while liver sections were fixed for histopathology or evaluated for GJIC using fluorescent cut-load dye. Results show a dose-dependent relationship with MC-LR exposure and hepatocellular hypertrophy, degradation, and necrosis. Clinical chemistry parameters alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and cholesterol increased significantly in MC-LR exposed mice. Clinical chemistry parameter analysis showed significantly increased susceptibility to MC-LR in females compared to males. Changes in GJIC were not noted, but localization of hepatotoxicity near the central veins and midlobular areas was seen. Future toxicity studies involving MCs should consider response differences across sexes, differing MC congeners, and combinatorial exposures involving other cyanotoxins.

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Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

Cited by 19 publications

References 51 publications

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

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

Water Blooms—A Potential Threat to Male Reproduction: Clues From Aquatics and Rodents

Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice

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