Hexachlorocyclohexane impairs human sperm motility by affecting lysine glutarylation and mitochondrial functions

Liu Yang; Guangquan Mei; Yebin Yang; Jiajun Cui; Shenglin Peng; Zhen Peng; Yimin Cheng

doi:10.1016/j.fct.2023.113991

Hexachlorocyclohexane impairs human sperm motility by affecting lysine glutarylation and mitochondrial functions

Food Chem Toxicol. 2023 Sep:179:113991. doi: 10.1016/j.fct.2023.113991. Epub 2023 Aug 16.

Authors

Liu Yang¹, Guangquan Mei², Yebin Yang³, Jiajun Cui⁴, Shenglin Peng⁵, Zhen Peng⁵, Yimin Cheng⁶

Affiliations

¹ Key Laboratory of Jiangxi University for Applied Chemistry and Chemical Biology, Yichun University, Yichun, China.
² Jiangxi Provincial Key Laboratory of Natural Active Pharmaceutical Constituents, Department of Chemistry and Bioengineering, Yichun University, Yichun, China; Key Laboratory of Jiangxi University for Applied Chemistry and Chemical Biology, Yichun University, Yichun, China.
³ College of Chemistry and Biological Engineering, Yichun University, Yichun, China.
⁴ Center for Translational Medicine, Department of Medicine, Yichun University, Yichun, China.
⁵ Yichun People's Hospital, Jiangxi Province, Yichun, China.
⁶ Jiangxi Provincial Key Laboratory of Natural Active Pharmaceutical Constituents, Department of Chemistry and Bioengineering, Yichun University, Yichun, China; Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, China; Center for Translational Medicine, Department of Medicine, Yichun University, Yichun, China. Electronic address: cym1169331029@outlook.com.

PMID: 37595880
DOI: 10.1016/j.fct.2023.113991

Abstract

Decreased sperm motility is a leading cause of male infertility and persistent organic pollutants are known to contribute significantly to the development of this disease. The effects of organochlorine pesticides such as hexachlorocyclohexane (HCH) on human sperm function and their mechanisms of action have received much attention, but are still not fully understood. Herein, we discovered that HCH has a concentration- and time-dependent inhibitory effect on human sperm motility in vitro. Moreover, HCH could reduce the levels of lysine glutarylation (Kglu) and glucose-6-phosphate dehydrogenase activity in sperm. Meanwhile, HCH could increase reactive oxygen species and thereby lead to mitochondrial depolarization and the down-regulation of adenosine triphosphate levels. In particular, we observed that sodium glutarate (Na-glu), the precursor of glutaryl-CoA, could alleviate the inhibitory effect of HCH on sperm Kglu levels, whereas the ROS scavenger N-acetyl-L-cysteine (NAC) had no effect. Intriguingly, both Na-glu and NAC were able to partially inhibit the HCH-induced increase in sperm ROS levels and impaired sperm motility. In conclusion, we propose that HCH inhibits sperm Kglu, leading to the disruption of mitochondrial energy metabolism, which in turn adversely affects sperm motility.

Keywords: Hexachlorocyclohexane; Human sperm; Lysine glutarylation; Mitochondrial dysfunction; Reactive oxygen species.

MeSH terms

Acetylcysteine
Hexachlorocyclohexane*
Humans
Lysine*
Male
Mitochondria
Reactive Oxygen Species
Semen
Sperm Motility

Substances

Hexachlorocyclohexane
Lysine
Reactive Oxygen Species
Acetylcysteine