Single microcystin exposure impairs the hypothalamic-pituitary-gonadal axis at different levels in female rats

Industrial progress has resulted in the improper disposal of wastewater containing pollutants into rivers and lakes ( S. Liu, He, and Li 2022; H. Z. Zhang et al., 2011). Consequently, this process has led to an increase in the incidence of cyanobacteria proliferation, resulting in the production of microcystins (MCs) and harmful algal blooms (HABs) (Du, 2019). HABs have had a detrimental impact on the public health and economy of nearby communities. Currently, approximately 60,000 people suffer from the consequences of HABs every year (S. Liu, He, and Li 2022). Since 2007, the cost of cleaning up Taihu Lake in China has exceeded 16 billion US dollars (H. Zhang et al., 2013). In California, USA, the fishing season was delayed by 6 months as a consequence of HABs, resulting in over $25 million in relief aid being distributed to impacted fishing industries (Free et al. 2022; Holland and Jerry, 2020).

MCs are a group of cyclic heptapeptides in which amino acid residues 2 and 4 vary as L-amino acids. To date, more than 279 MC variants have been reported (Bouaïcha, 2019). Among these variants, MCs that contain leucine (L) at position 2 and arginine (R) at position 4 (MC-LR) are the most extensively studied due to their toxicity and prevalence (Mantzouki et al., 2018). MC-LR in water reservoirs has been reported to have a half-life of approximately one week. In some cases, a lag phase for biodegradation lasting from 9 to 14 days has been reported (Edwards et al., 2008; WHO 2020). However, the half-life of MC-LR in a natural system is estimated at 90–120 days per meter of water depth (Welker and Steinberg 2000). The half-life of MCs is species-specific, ranging from 0.7 to 3.5 days or 2.8–8.4 days in carp (Adamovský, 2007). MC-LR appears to be rapidly absorbed from the gastrointestinal tract into the bloodstream and is quickly transported to the liver, with MC-LR reaching the liver within 1 h after exposure and reaching maximum levels 3 h after exposure. The half-life of MCs in the blood is 3.3 h (Tencalla and Dietrich 1997).

MCs induce a variety of toxic responses in numerous organs, including the liver, kidney, lungs, and reproductive organs (Chen et al., 2016; Gorham et al., 2020; McLellan and Manderville 2017). MCs can enter cells through organic anion transporting polypeptides, leading to cytotoxic effects such as DNA damage, as well as dysfunction in the cytoskeleton, mitochondria, and endoplasmic reticulum, which are associated with inflammation and oxidative stress (Chen and Xie 2016). The primary route of human MC exposure is through the oral ingestion of contaminated water or food supplies (Díez-Quijada and Leticia, 2019; Vidal et al., 2017). The World Health Organization (WHO) recommends a lower provisional guideline value of 1.0 μg/L for MC-LR in drinking water (Buratti et al., 2017; WHO 2020). This recommendation is based on a 13-week study of MC-LR, in which a no-observed-adverse-effect level (NOAEL) of 40 μg/kg/day was established for pathology evaluation in mouse liver (Fawell et al., 1994). An uncertainty factor of 1000 was applied to calculate the tolerable daily intake (TDI) of 0.04 μg/kg/day (Fawell et al., 1994; WHO 2020). Despite concerns about MC-LR's impact on health, a wide range of MC-LR concentrations are still detected in water and fish/seafood samples across different continents, including America (water: 0.08–6.76 μg/L; fish/seafood: 1–11.54 ng/g), Africa (water: 0–2.59 mg/L; fish/seafood: not reported), Asia (water:0.03–31.77 μg/L; fish/seafood: 1.44–915.89 ng/g), and Europe (water: 0.006–62.4 μg/L; fish/seafood: 0.049–0.85 ng/g) (Amé and Valeria, 2010; Deblois et al., 2008; Fewer et al., 2009; Hu et al., 2015; Jia et al. 2016; Sedda et al., 2016; Shang et al., 2015; Simiyu et al., 2018; Singh and Kumar Asthana, 2014; Šulčius et al., 2015).

Exposure to MC-LR has been demonstrated to disrupt ovarian function, leading to altered estrous cyclicity, abnormal folliculogenesis, changes in sex hormone profiles, and increased ovarian oxidative stress and apoptosis (Chen et al., 2021; Liu, 2018; Wu et al., 2014). However, there is limited information available regarding the effects of MC on ovarian reserve, lipid accumulation, inflammation, angiogenesis, and metabolic parameters, such as body weight, serum lipid levels, and glucose metabolism. Additionally, little is known about how MC exposure affects HPG axis function in response to inflammation or the estrogen-negative feedback response following ovariectomy. Therefore, this study was designed to investigate the hypothesis that single exposure to MC-LR at environmentally relevant doses can lead to metabolic and HPG axis irregularities in female rats.

留言 (0)

沒有登入
gif