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Microcystin-LR induces ovarian injury and apoptosis in mice via activating apoptosis signal-regulating kinase 1-mediated P38/JNK pathway.

Authors :
Du X
Liu H
Liu X
Chen X
Yuan L
Ma Y
Huang H
Wang Y
Wang R
Zhang S
Tian Z
Shi L
Zhang H
Source :
Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2021 Apr 15; Vol. 213, pp. 112066. Date of Electronic Publication: 2021 Feb 18.
Publication Year :
2021

Abstract

As an emerging pollutant in the aquatic environment, microcystin-LR (MC-LR) can enter the body through multiple pathways, and then induce apoptosis and gonadal damage, affecting reproductive function. Previous studies focused on male reproductive toxicity induced by MC-LR neglecting its effects on females. The apoptotic signal-regulated kinase 1 (ASK1) is an upstream protein of P38/JNK pathway, closely associated with apoptosis and organ damage. However, the role of ASK1 in MC-LR-induced reproductive toxicity is unclear. Therefore, this study investigated the role of ASK1 in mouse ovarian injury and apoptosis induced by MC-LR. After MC-LR exposure, ASK1 expression in mouse ovarian granulosa cells was increased at the protein and mRNA levels, and decreased following pretreatment by antioxidant N-acetylcysteine, suggesting that MC-LR-induced oxidative stress has a regulatory role in ASK1 expression. Inhibition of ASK1 expression with siASK1 and NQDI-1 could effectively alleviate MC-LR-induced mitochondrial membrane potential damage and apoptosis in ovarian granulosa cells, as well as pathological damage, apoptosis and the decreased gonadal index in ovaries of C57BL/6 mice. Moreover, the P38/JNK pathway and downstream apoptosis-related proteins (P-P38, P-JNK, P-P53, Fas) and genes (MKK4, MKK3, Ddit3, Mef2c) were activated in vivo and vitro, but their activation was restrained after ASK1 inhibition. Data presented herein suggest that the ASK1-mediated P38/JNK pathway is involved in ovarian injury and apoptosis induced by MC-LR in mice. It is confirmed that ASK1 has an important role in MC-LR-induced ovarian injury, which provides new insights for preventing MCs-induced reproductive toxicity in females.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2414
Volume :
213
Database :
MEDLINE
Journal :
Ecotoxicology and environmental safety
Publication Type :
Academic Journal
Accession number :
33610944
Full Text :
https://doi.org/10.1016/j.ecoenv.2021.112066