Oncotarget

Research Papers: Immunology:

B7-H3 promoted proliferation of mouse spermatogonial stem cells via the PI3K signaling pathway

Xuedong Wei, Kai Li, Guangbo Zhang, Yuhua Huang, Jinxing Lv, Miao Li, Lun Zhao, Caibin Fan, Jinxian Pu, Jianquan Hou and Hexing Yuan _

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Oncotarget. 2018; 9:1542-1552. https://doi.org/10.18632/oncotarget.23457

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Abstract

Xuedong Wei1,*, Kai Li1,2,*, Guangbo Zhang3, Yuhua Huang1, Jinxing Lv1, Miao Li1, Lun Zhao1, Caibin Fan2, Jinxian Pu1, Jianquan Hou1 and Hexing Yuan1

1 Department of Urology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China

2 Department of Urology, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of China

3 Department of Clinical Immunology Laboratory, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Hexing Yuan, email:

Jianquan Hou, email:

Keywords: B7-H3; testis; mouse spermatogonial stem cell; proliferation; PI3K pathway; Immunology

Received: May 18, 2017 Accepted: December 06, 2017 Published: December 20, 2017

Abstract

Objective: We found seminal B7-H3 was associated with human sperm concentration. However, the mechanism is unclear. The purpose of this study was to investigate the expression of B7-H3 in mouse testis and determine the effects of B7-H3 on the proliferation of mouse spermatogonial stem cells (SSCs) and the underlying mechanisms.

Methods: B7-H3 expression in the testis of mice at different ages (3 weeks, 8 weeks, 4 months and 9 months) was detected by western blot and immunohistochemistry. CCK-8 were used to measure mouse SSCs proliferation after incubation with different concentrations of B7-H3 for 1-72 h in vitro. Flow cytometry was used to analyze the cell cycle of mouse SSCs after incubation with different concentrations of B7-H3 for 48 and 72 h. The signaling pathways involved were assessed by western blot.

Results: Four-month-old mice had the highest expression of B7-H3 in the testis, while 3-week-old mice had the lowest expression of B7-H3. B7-H3 was predominantly detected on the membrane and in the cytoplasm of Sertoli cells. Furthermore, B7-H3 promoted mouse SSCs proliferation and increased the percentage of cells in S+G2/M phase in a time- and dose-dependent manner in vitro. These effects were inhibited by LY294002, indicating the involvement of the phosphoinositide 3-kinase signaling pathway.

Conclusions: The expression of B7-H3 in mouse testis, especially Sertoli cells, was associated with mouse age. In vitro, B7-H3 promoted the proliferation and accelerated the cell cycle of mouse SSCs via the PI3K pathway, indicating a critical role of B7-H3 expressed by Sertoli cells in mouse spermatogenesis.


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