N-acetylcysteine alleviated bisphenol A-induced testicular DNA hypermethylation of rare minnow (Gobiocypris rarus) by increasing cysteine contents

Cong Yuan; Lihong Wang; Long Zhu; Benhui Ran; Xue Xue; Zaizhao Wang

doi:10.1016/j.ecoenv.2019.02.035

N-acetylcysteine alleviated bisphenol A-induced testicular DNA hypermethylation of rare minnow (Gobiocypris rarus) by increasing cysteine contents

Ecotoxicol Environ Saf. 2019 May 30:173:243-250. doi: 10.1016/j.ecoenv.2019.02.035. Epub 2019 Feb 14.

Authors

Cong Yuan¹, Lihong Wang², Long Zhu², Benhui Ran², Xue Xue², Zaizhao Wang³

Affiliations

¹ College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi 712100, China; Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
² College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi 712100, China.
³ College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi 712100, China. Electronic address: zzwang@nwsuaf.edu.cn.

PMID: 30772714
DOI: 10.1016/j.ecoenv.2019.02.035

Abstract

Ubiquitous BPA exposure resulted in DNA methylation errors and oxidative stress. Numerous studies have demonstrated that oxidative stress can lead to changes in DNA methylation levels and supplementation with antioxidants, including N-acetylcysteine (NAC), was able to restore these changes. Our previous study supposed that BPA-induced de novo synthesis of glutathione (GSH) promoted DNA methylation process in Gobiocypris rarus testes. To validate this conjecture and explore the protective effects of NAC on BPA toxicity, the present study was carried out. Adult male G. rarus was treated with 225 μg L^-1 BPA and/or NAC for 7 days. The sperm motility and DNA integrity of G. rarus were determined. Meanwhile, the levels of 5-methylcytosine (5mC), GSH, hydrogen peroxide (H₂O₂), DNA methyltransferase proteins (DNMTs), γ-glutamyl cysteine synthetase (GCS), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), nicotinamide adenine dinucleotide phosphate (NADPH) and cysteine in the testes were detected. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Results indicated that NAC addition resulted in increase of cysteine contents and partially inhibited the BPA-induced DNA hypermethylation of G. rarus testes. In addition, the changes in DNA methylation levels in the testes after BPA and/or NAC treatment might be controlled by DNA methylation process that mediated by DNMTs. Moreover, BPA exposure caused oxidative stress in the testes and the elimination of H₂O₂ might be mainly accomplished by CAT while it changed to mainly through GPx after NAC supplement. Finally, the positive response of testicular antioxidant enzyme system and the antioxidant activity of NAC itself protected sperm motility and DNA integrity from oxidative damage in each group.

Keywords: Bisphenol A; DNA methylation; Gobiocypris rarus; N-acetylcysteine; Oxidative stress.

MeSH terms

Acetylcysteine / pharmacology*
Animals
Antioxidants / pharmacology*
Benzhydryl Compounds / toxicity*
Cyprinidae / metabolism*
DNA Methylation / drug effects
Male
Phenols / toxicity*
Sperm Motility / drug effects
Testis / drug effects
Testis / metabolism

Substances

Antioxidants
Benzhydryl Compounds
Phenols
bisphenol A
Acetylcysteine