College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Center of Reproductive Medicine, Amsterdam Research Institute Reproduction and Development, Academic Medical Center, University of Amsterdam 1105AZ, Amsterdam, Netherlands.
Zool Res. 2023 May 18;44(3):505-521. doi: 10.24272/j.issn.2095-8137.2022.440.
Bacterial or viral infections, such as , mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that plays an important role in regulating testicular immune homeostasis. Knockdown of in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that positively regulated the expression of , an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified - -NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.
细菌或病毒感染，如腮腺炎病毒、单纯疱疹病毒和寨卡病毒，破坏睾丸的免疫稳态，导致精子发生障碍和不育。值得注意的是，最近的研究表明，SARS-CoV-2 可以感染男性性腺并破坏支持细胞和间质细胞，导致男性生殖功能障碍。由于抗生素治疗存在许多副作用，因此寻找炎症损伤的替代治疗方法仍然至关重要。在这里，我们发现 在调节睾丸免疫稳态中起着重要作用。在雄性小鼠中敲低 会抑制精子发生，导致生精小管广泛的炎症反应，并导致生精上皮细胞丢失。染色质免疫沉淀测序 (ChIP-seq) 和 RNA 测序 (RNA-seq) 显示 正向调节 的表达， 是受体酪氨酸激酶 (RTK) 信号通路的抑制蛋白。此外，免疫沉淀-质谱 (IP-MS) 和共免疫沉淀 (Co-IP) 分析表明 SPRY1 与核因子 kappa B1 (NF-κB1) 结合，以阻止 p65 的核转位，抑制 NF-κB 信号的激活，防止睾丸中过度的炎症反应，并保护血睾屏障的完整性。鉴于在调节睾丸免疫稳态中鉴定出的这一新的 - -NF-κB 轴机制，我们的研究为人类和家畜生殖疾病的预防和治疗开辟了新途径。
