Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.500
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
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.
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.
To study the effect and potential mechanism of NP on SSCs.
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.
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.
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.
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.