Published online Nov 26, 2021. doi: 10.4252/wjsc.v13.i11.1797
Peer-review started: July 19, 2021
First decision: August 15, 2021
Revised: August 28, 2021
Accepted: September 15, 2021
Article in press: September 15, 2021
Published online: November 26, 2021
Human spermatogonial stem cells (SSCs) are the basis of spermatogenesis. However, little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.
To investigates the mechanisms involved in the proliferation of human SSCs.
To investigate the functions and mechanisms of mitogen-activated protein kinase kinase 7 (MKK7) during proliferation and apoptosis in human SSCs.
The expression of MKK7 in human testis was identified using immunohistochemistry and western blotting (WB). MKK7 was knocked down using small interfering RNA, and cell proliferation and apoptosis were detected by WB, EdU, cell counting kit-8 and fluorescence-activated cell sorting. After bioinformatic analysis, the interaction of MKK7 with c-Jun N-terminal kinases (JNKs) was verified by protein co-immunoprecipitation and WB. The phosphorylation of JNKs was inhibited by SP600125, and the phenotypic changes were detected by WB, cell counting kit-8 and fluorescence-activated cell sorting.
MKK7 is mainly expressed in human SSCs, and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis. MKK7 mediated the phosphorylation of JNKs, and after inhibiting the phosphorylation of JNKs, the phenotypic changes of the cells were similar to those after MKK7 downregulation. The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis, suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.
MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs. Abnormal expression of MKK7 may impair human spermatogenesis.
This study intended to reveal the role and regulatory mechanism of MKK7 in the regulation of SSC development and spermatogenesis in humans, which can provide a scientific basis for the etiological interpretation and molecular diagnosis of male infertility. It also provided new molecular targets for the clinical treatment of male infertility and the development of contraceptives.