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

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

  • Ecotoxicol Environ Saf. 2021 Apr 15;213:112066. doi: 10.1016/j.ecoenv.2021.112066.
Xingde Du 1 Haohao Liu 1 Xiaohui Liu 2 Xinghai Chen 3 Le Yuan 1 Ya Ma 1 Hui Huang 1 Yueqin Wang 1 Rui Wang 1 Shiyu Zhang 1 Zhihui Tian 1 Linjia Shi 1 Huizhen Zhang 4
Affiliations

Affiliations

  • 1 College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
  • 2 School of Basic Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China.
  • 3 Department of Chemistry and Biochemistry, St Mary's University, San Antonio, TX 78228, USA.
  • 4 College of Public Health, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
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.

Keywords

Apoptosis; Apoptosis signal-regulating kinase 1; Microcystin-LR; Ovarian injury; Reproductive toxicity.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19566
    98.03%, ASK1 Inhibitor