PDF(Pubmed)
Abstract：
The reproductive homeobox X-linked (Rhox) genes encode transcription factors that are expressed selectively in reproductive tissues including the testis, epididymis, ovary, and placenta. While many Rhox genes are expressed in germ cells in the mouse testis, only Rhox8 is expressed exclusively in the Sertoli cells during embryonic and postnatal development, suggesting a possible role of Rhox8 in embryonic gonad development. Previously, Sertoli cell-specific knockdown of RHOX8 resulted in male subfertility due to germ cell defects. However, this knockdown model was limited in examining the functions of Rhox8 as RHOX8 knockdown occurred only postnatally, and there was still residual RHOX8 in the testis. In this study, we generated new Rhox8 knockout (KO) mice using the CRISPR/Cas9 system. Sex determination and fetal testis development were apparently normal in mutant mice. Fertility analysis showed a low fecundity in Rhox8 KO adult males, with disrupted spermatogenic cycles, increased germ cell apoptosis, and reduced sperm count and motility. Interestingly, Rhox8 KO testes showed an increase in testis size with dilated seminiferous tubules and rete testis, which might be affected by efferent duct (ED) Rhox8 ablation dysregulating the expression of metabolism and transport genes in the EDs. Taken together, the data presented in this study suggest that Rhox8 in the Sertoli cells is not essential for sex determination and embryonic testis differentiation but has an important role in complete spermatogenesis and optimal male fertility.
摘要：
生殖同源盒X连锁（Rhox）基因编码转录因子，这些转录因子在包括睾丸在内的生殖组织中选择性表达。附睾,子房,和胎盘。虽然许多Rhox基因在小鼠睾丸的生殖细胞中表达，只有Rhox8在胚胎和出生后发育期间在支持细胞中完全表达，提示Rhox8在胚胎性腺发育中的可能作用。以前,由于生殖细胞缺陷，RHOX8的支持细胞特异性敲除导致男性不育。然而,该敲低模型在检查Rhox8的功能方面受到限制，因为RHOX8敲低仅在出生后发生，睾丸中仍有残留的RHOX8。在这项研究中,我们使用CRISPR/Cas9系统产生了新的Rhox8敲除(KO)小鼠。突变小鼠的性别决定和胎儿睾丸发育显然正常。生育力分析显示，Rhox8KO成年男性的繁殖力较低，生精周期中断，生殖细胞凋亡增加，精子数量和活力降低。有趣的是,Rhox8KO睾丸显示睾丸大小增加，精细管和睾丸网扩张，这可能是由于输出管Rhox8消融失调影响了输出管中代谢和转运基因的表达。一起来看,这项研究中提供的数据表明，Sertoli细胞中的Rhox8对于性别决定和胚胎睾丸分化不是必需的，但在完整的精子发生和最佳的男性生育能力中具有重要作用。
