Abstract
Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by which oxidative stress acts on MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy. In the present study, immortalized murine ovarian granular cells (KK-1 cells) were exposed to 8.5, 17, and 34 μg/mL (IC50) of MC-LR with or without N-acetyl-l-cysteine (NAC, 10 mM) for 24 h, and C57BL/6 mice were treated with 12.5, 25.0, and 40.0 μg/kg⋅bw of MC-LR with or without NAC (200 mg/kg⋅bw) for 14 days. The results revealed that MC-LR could induce cells apoptosis and morphologic changes in ovarian tissues, induce oxidative stress by stimulating the generation of reactive oxygen species (ROS), destroying antioxidant capacity, and subsequently trigger ERs and autophagy by inducing the hyper-expression of ATG12, ATG5, ATG16, EIF2α (phosphorylated at S51), CHOP, XBP1, GRP78, Beclin1, and PERK (Thr980). Furthermore, NAC pretreatment partly inhibited MC-LR-induced ERs and autophagy via the PERK/ATG12 and XBP1/Beclin1 pathways. These results suggest that oxidative stress mediated MC-LR-induced ERs and autophagy in KK-1 cells and C57BL/6 mice ovaries. Therefore, oxidative stress plays an important role in female toxicity induced by MC-LR.
Highlights
Due to the aggravating environmental pollution, including water pollution, the relationship between the decline in human fertility and environmental exposure has attracted worldwide attention
microcystin-leucine arginine (MC-LR) band was found in low-dose group (In vitro: 8.5 μg/mL, In vivo: 12.5 μg/kg), higher-dose group and NAC+MC-LR group, which indicated that MC-LR could enter into KK-1 cells or ovarian tissue
The present study revealed that oxidative stress is essential for MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy in KK-1 cells and C57BL/6 mice ovaries
Summary
Due to the aggravating environmental pollution, including water pollution, the relationship between the decline in human fertility and environmental exposure has attracted worldwide attention. MC is a family of cyclic heptapeptide intracellular toxins released by cyanobacteria in eutrophication water, and has been regarded as a major health hazard to humans. MC-LR-Induced ERs and Autophagy (Puddick et al, 2014; Qi et al, 2015; Bouhaddada et al, 2016), and microcystin-leucine arginine (MC-LR) is one of the most common and potent variants (Kaasalainen et al, 2012). MC is soluble in water, heat-resistant and chemically stable (Merel et al, 2013; Pavagadhi and Balasubramanian, 2013), and it is difficult to remove from nature water used for drinking water supply by existing processing methods. It is hard to prevent harm when humans and animals are exposed to MC via diet, breathing, and skin contact (Zhang et al, 2009; Zhang D. et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
