Affiliation:
1. School of Public Health Lanzhou University Lanzhou China
2. Henan Institute of Advanced Technology Zhengzhou University Zhengzhou China
3. Key Laboratory of Materials Physics and Anhui Key Laboratory of Nanomaterials and Nanotechnology Institute of Solid State Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences Hefei China
4. Reproductive Medicine Center Gansu Provincial Maternity and Child‐care Hospital Lanzhou China
Abstract
AbstractThe present study was designed to investigate the role of miR‐708‐5p/p38 mitogen‐activated protein kinase (MAPK) pathway during the mechanism of selenium nanoparticles (Nano‐Se) against nickel (Ni)‐induced testosterone synthesis disorder in rat Leydig cells. We conducted all procedures based on in vitro culture of rat primary Leydig cells. After treating Leydig cells with Nano‐Se and NiSO4 alone or in combination for 24 h, we determined the cell viability, reactive oxygen species (ROS) levels, testosterone production, and the protein expression of key enzymes involved in testosterone biosynthesis: steroidogenic acute regulatory (StAR) and cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A1). The results indicated that Nano‐Se antagonized cytotoxicity and eliminated ROS generation induced by NiSO4, suppressed p38 MAPK protein phosphorylation and reduced miR‐708‐5p expression. Importantly, we found that Nano‐Se upregulated the expression of testosterone synthase and increased testosterone production in Leydig cells. Furthermore, we investigated the effects of p38 MAPK and miR‐708‐5p using their specific inhibitor during Nano‐Se against Ni‐induced testosterone synthesis disorder. The results showed that Ni‐inhibited testosterone secretion was alleviated by Nano‐Se co‐treatment with p38 MAPK specific inhibitor SB203580 and miR‐708‐5p inhibitor, respectively. In conclusion, these findings suggested Nano‐Se could inhibit miR‐708‐5p/p38 MAPK pathway, and up‐regulate the key enzymes protein expression for testosterone synthesis, thereby antagonizing Ni‐induced disorder of testosterone synthesis in Leydig cells.
Funder
Natural Science Foundation of Gansu Province
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine