In the past decade, environmental problems, which have attracted worldwide attention, are particularly serious in developing countries. Water bloom is one of the most serious environmental issues (Zhang et al. 2011). Cyanobacteria blooms have caused the death of a large number of fishes and lead to extremely serious damage to the marine ecosystem. Although the Chinese government has been controlling cyanobacteria blooms in Taihu Lake for a long time, they are still rampant, which have drawn the attention of the World Health Organization (Wang et al. 2013). Although we are not directly exposed to MCs, they can enter the human body through the consumption of aquatic animals, including fish, frogs, plankton or aquatic plants, and are finally distributed in various organs of the body (Meng et al. 2020).
To our knowledge, this is the first meta-analysis that focuses on the negative effects of MC-LR on the male reproductive system. We quantitatively evaluated the effects of MCs on multiple parameters of the male reproductive system. We evaluated a total of 15 publications to summarise their findings. Amongst them, 9 focused on the effects of MCs on the rodent reproductive system, and the rest focused on fishes. The metrics included sperm count, abnormal sperm rate, sperm motility, testis weight, serum testosterone, serum estradiol, and serum FSH and LH. According to the results of the meta-analysis, MCs can lead to dysfunction of the male reproductive system, indicating that cyanobacteria bloom pollution should be treated as soon as possible.
In total, nine individual meta-analyses in our systematic review were undertaken to calculate the pooled SMD of MC exposure. Amongst them, seven meta-analyses reached statistical significance (P < 0.05), and four meta-analyses showed significant positive associations. According to the data of rodent studies, sperm count (SMD = -1.7426 (95% CI: -2.2098 to -1.2754)), sperm motility (SMD = -2.8822 (95% CI: -3.9811 to -1.7834)) abnormal sperm rate (SMD = 1.6714 (95% CI: 0.9702 to 2.3726)) and serum FSH (SMD = 0.4707 (95% CI: 0.0659 to 0.8756)) demonstrated significant positive associations. According to the data of fish studies, significant positive associations were found in serum testosterone (SMD = 0.5521 (95% CI: 0.1652; 0.9391)) and serum estradiol (SMD = 0.6398 (95% CI: 0.1896 to 1.0900)). In the two remaining meta-analyses, although no significant correlation was found, serum testosterone and serum LH were still affected by MCs.
Most meta-analyses had a high degree of heterogeneity, which is typical in this research field. This may be attributed to factors such as differences in research design, drug purity and individual differences of experimental subjects. When we conducted subgroup analysis based only on the exposure dose or exposure time, the heterogeneity of the study decreased.
Interestingly, when we analysed the dose–response relationship, most of the results were consistent with our speculation. With the increase of exposure time and dose, the sperm count and sperm motility showed a downward trend. However, the changes of serum sex hormones, such as testosterone, FSH and LH, were not obvious with the increase of exposure time and dose. Interestingly, after exposure to low dose of MCs, a small increase in serum testosterone, FSH and LH was observed, whereas high dose of MC-LR significantly decreased the serum testosterone, FSH and LH, which suggests that high MC-LR concentration has strong toxicity.
Jia et al. found a large amount of MC-LR accumulation in the testes of Rana nigromaculata by immunofluorescence staining. They found that the down-regulation of Hsd17b3 gene expression led to the inhibition of T synthesis, and that the up-regulation of CYP19A1 gene expression directly stimulated the transformation of testosterone to estradiol (Zhang et al. 2013). In another study, the endocrine function of the male black spot frog was affected after exposure to 1 µg/LMC in fresh water (Chen et al. 2011). MCs can affect the neurological function, sperm count, sperm motility, sperm viability, sperm progressive motility and sperm viability of rats. Histological examination showed that the testis atrophied and the structure of seminiferous tubules was damaged in the MC group (Li et al. 2006). The main function of Leydig cells is to produce androgen, which is necessary for spermatogenesis, maturation and the maintenance of libido (Wang et al. 2014). A decrease in testosterone may reflect damage of interstitial cells caused by MC-LR exposure. As noted above, MCs likely pass through the blood–testis barrier and affect the spermatogenesis of the testis and the production of testosterone, resulting in the weakening of libido in male rats.
At present, the mechanism by which MC-LR affects the male reproductive system is unclear. Fish studies have found that MC-LR may delay gonadal maturation by interfering with the growth hormone/insulin-like growth factor system. Moreover, the gonadal development of males was found to be more easily affected by MC-LR than that of females (Hou et al. 2017). However, Qin Qiao et al. found that female zebrafish are more vulnerable to MC-LR exposure than males (Qiao et al. 2013). In mouse studies, MC-LR can induce immune response of Sertoli cells, germ cells and interstitial cells by activating phosphatidylinositol 3-kinase/AKT/nuclear factor kappa B, thus producing proinflammatory cytokines and chemokines and damaging the function of the main testicular cells, which is crucial to the spermatogenic function and testosterone level of the testis (Chen et al. 2017).
This study has several limitations. The relationship between MC exposure and male reproductive system damage was affected by many factors, which may be the cause of heterogeneity, and the exposure time and dose may be the source of heterogeneity. In addition, no studies have focused on daily exposure of MCs in humans. Thus, the optimal exposure dose of MCs is still unknown. Despite these limitations, our findings have practical implications. We evaluated the effects of MC exposure on the reproductive system of mice and fish. In addition, we conducted several subgroup analyses to explore the effects of several key factors on the study. Furthermore, the dose–response relationship curve can be used to intuitively observe the relationship between short-term and long-term exposure, as well as between low-dose and high-dose exposure.