Overexpression of PD-L1 causes germ cells to slough from mouse seminiferous tubules via the PD-L1/PD-L1 interaction

作者：Fang, Lian; Feng, Rui; Liang, Weiye; Liu, Fang-Fang; Bian, Gan-lan; Yu, Caiyong; Guo, Hongmin; Cao, Yihui; Liu, Mingkai; Zuo, Jia; Peng, Yinglong; Zhao, Jie; Sun, Rui-Xia; Shan, Jiajie^*; Wang, Jian^*

来源：Journal of Cellular and Molecular Medicine, 2022, 26(10): 2908-2920.

DOI：10.1111/jcmm.17305

• adhesion
• germ cells
• PD-L1
• transgenic

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.

• 单位
  中国人民解放军第四军医大学; 河北医科大学; 西北工业大学