Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2020; 12(6): 500-513
Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.500
Cytotoxicity of nonylphenol on spermatogonial stem cells via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway
Jun-Hao Lei, Wen Yan, Chun-Hua Luo, Yu-Ming Guo, Yang-Yang Zhang, Xing-Huan Wang, Xin-Jun Su
Jun-Hao Lei, Chun-Hua Luo, Yu-Ming Guo, Yang-Yang Zhang, Xing-Huan Wang, Xin-Jun Su, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
Wen Yan, Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
Xing-Huan Wang, Center for Evidence-based and Translational Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: Guo YM, Zhang YY and Yan W collected and analyzed the data; Lei JH and Luo CH drafted the manuscript; Su XJ and Wang XH commented in detail on the manuscript; All authors read and approved the final manuscript.
Supported by Health and Family Planning Committee Joint Fund Project of Hubei Province, No. WJ2018H0020; Fundamental Research Funds for the Central Universities, No. 2042016kf0187 and No. 2042017kf0068; and Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund, No. znpy2016022.
Institutional animal care and use committee statement: All animal experiments conformed to the Guidelines for Animal Care and Use of the Model Animal Research Institute at Wuhan Myhalic Biotechnology Co., Ltd. (approval No. HLK-20180522-01).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xin-Jun Su, MA, Chief Doctor, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, Donghu Road No. 169, Wuhan 430071, Hubei Province, China. 13697326659@139.com
Received: December 18, 2019
Peer-review started: December 18, 2019
First decision: February 20, 2020
Revised: March 17, 2020
Accepted: April 8, 2020
Article in press: April 8, 2020
Published online: June 26, 2020
ARTICLE HIGHLIGHTS
Research background

Infertility has become a social problem that needs to be solved urgently in the world. Apart from the infertility caused by female causes, infertility caused by male oligozoospermia has gradually been valued. Previous studies have confirmed that nonylphenol (NP) widely used in daily life can reduce male sperm counts, but the underlying mechanism is still unclear. Studying the specific mechanism of NP-induced oligospermia could provide some ideas for the treatment of NP-induced oligospermia.

Research motivation

NP has been shown to affect sperm activity, but the mechanism is currently unknown. Spermatogonial stem cells (SCCs) can eventually differentiate into sperm. We aim to study whether NP can affect the proliferation, differentiation and potential mechanism of SSCs in order to provide ideas for clinical treatment of male oligospermia caused by NP.

Research objectives

To study the effect and potential mechanism of NP on SSCs.

Research methods

SSCs were treated with NP at 0, 10, 20 or 30 μmol. MTT was used to detect the effect of NP on the proliferation of SSCs. Flow cytometry, reverse transcription polymerase chain reaction and western blot were used to detect the effect of NP on the proliferation, apoptosis, oxidative stress and stemness maintenance of SSCs. The effects of NP on phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was also measured by western blot.

Research results

Different concentrations of NP (10, 20 or 30 μmol) could inhibit the proliferation of SSCs, reduce the expression of cell differentiation and stem maintenance related factors and promote apoptosis and the release of oxidative stress factors. We further examined the effect of NP on the PI3K/AKT/mTOR pathway, and the results showed that NP can significantly inhibit the activity of the PI3K/AKT/mTOR pathway. Among all NP concentrations, 30 μmol had the greatest effect.

Research conclusions

NP reduced the proliferation, differentiation and stemness maintenance of SSCs while promoting apoptosis and oxidative stress, and the mechanism may be related to the PI3K/AKT/mTOR pathway, providing a potential method for the treatment of male infertility.

Research perspectives

In this study, we demonstrated in vitro that NP could promote apoptosis and oxidative stress of SSCs and reduce the proliferation, differentiation and stem maintenance of SSCs, and the mechanism may be related to the PI3K/AKT/mTOR pathway. Therefore, we speculate that promoting the activity of the PI3K/AKT/mTOR pathway may help relieve male oligozoospermia caused by NP, and we will use PI3K/AKT/mTOR pathway agonist to verify our conjecture in the following studies in vivo.