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

PD-L1 过度表达通过 PD-L1/PD-L1 相互作用导致生殖细胞从小鼠曲细精管脱落

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

Abstract

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.

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