Yu Jun-Jie, Qi Hong-Yu, Zhao Zhan, Yang Yu, Zhang Shuang-Yi, Tan Fu-Qing, Yang Wan-Xi
The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
School of Medicine, Zhejiang University, Hangzhou 310003, China.
Int J Mol Sci. 2025 Jun 4;26(11):5378. doi: 10.3390/ijms26115378.
Hedgehog (HH) signaling plays important roles in the development of the nervous system (Sonic hedgehog), bone, cartilage (Indian Hedgehog) and testis (Desert Hedgehog). Research on HH and testes has mostly been conducted in -knockout mice and rats, etc. The relationship between HH and cellular junctions has mostly been found in the nervous system and intestine. However, few research studies concerning the link between HH signaling and cell junctions in testis function have been reported. We identified the members of HH signaling that are involved in testes: , , , and . has only one homolog in and is expressed in several types of germ cells in the testes. We found that Kif27 colocalized with Ci in the testes. The knockdown of induced enlarged interstitial spaces of the seminiferous tubules. A biotin-streptavidin immunofluorescence experiment indicated that the hemolymph-testis barrier (HTB) was disrupted. Western blot results showed that pinin, HH signaling and cell proliferation- and apoptosis-related protein levels were downregulated. Further immunofluorescent results showed the dislocation of several junction proteins, the abnormality of F-actin and the slowdown of germ cell proliferation and apoptosis. While β-catenin entered the spermatocyte nucleus, it did not activate Wnt-β-catenin signaling, which indicated that the disturbance of the cell cycle in germ cells was not caused by Wnt-β-catenin signaling. In summary, HH signaling plays some roles beyond our understanding in the regulation of the HTB and the germ cell cycle in testes.
刺猬信号通路（HH）在神经系统（音猬因子）、骨骼、软骨（印度刺猬因子）和睾丸（沙漠刺猬因子）的发育中发挥着重要作用。关于HH与睾丸的研究大多是在基因敲除小鼠和大鼠等动物中进行的。HH与细胞连接的关系大多在神经系统和肠道中被发现。然而，关于HH信号通路与睾丸功能中细胞连接之间联系的研究报道很少。我们确定了参与睾丸的HH信号通路成员： 、 、 、 和 。 在 中只有一个同源物，并且在睾丸中的几种生殖细胞类型中表达。我们发现Kif27在睾丸中与Ci共定位。 的敲低导致生精小管间质空间增大。生物素 - 链霉亲和素免疫荧光实验表明血睾屏障（HTB）被破坏。蛋白质印迹结果显示桥粒斑蛋白、HH信号通路以及与细胞增殖和凋亡相关的蛋白质水平下调。进一步的免疫荧光结果显示几种连接蛋白错位、F - 肌动蛋白异常以及生殖细胞增殖和凋亡减缓。虽然β - 连环蛋白进入精母细胞核，但它并未激活Wnt - β - 连环蛋白信号通路，这表明生殖细胞中细胞周期的紊乱不是由Wnt - β - 连环蛋白信号通路引起的。总之，HH信号通路在睾丸血睾屏障和生殖细胞周期的调节中发挥着一些超出我们认知的作用。
