Chiga Masahiko, Ohmori Tomoko, Ohba Takashi, Katabuchi Hidetaka, Nishinakamura Ryuichi
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Int J Dev Biol. 2014;58(9):663-8. doi: 10.1387/ijdb.140261rn.
The Müllerian duct gives rise to female reproductive organs, such as the oviduct and uterus. During gestation, the Wolffian duct, which generates male reproductive organs and the kidney, is formed, and the Müllerian duct then elongates caudally along the preformed Wolffian duct. Anatomical separation of these two ducts in chick embryos demonstrated that the Wolffian duct is required for Müllerian duct formation. Likewise, a few reports supported this notion in mice, including studies on Wnt9b mutant mice and Wolffian duct-specific Lhx1 deletion. However, anatomical ablation of the Wolffian duct has not been established in mice. In this study, we addressed the importance of the interaction between these two reproductive ducts, by generating mice that specifically expressed a diphtheria toxin subunit in the Wolffian duct. While this genetic ablation of the Wolffian duct resulted in kidney hypoplasia/agenesis in both male and female mutant mice, the female mutant mice lacked the uterus, which is derived from the Müllerian duct. At mid-gestation, the Müllerian duct was truncated at the level where the mutant Wolffian duct was prematurely terminated, meaning that Müllerian duct elongation was dependent on the preformed Wolffian duct. However, Wnt9b expression in the Wolffian duct and the resultant canonical Wnt activity, as well as Lhx1 expression, were not affected in the mutant mice. These results suggest that the Wolffian duct regulates Müllerian duct elongation by currently unidentified mechanisms that are independent of canonical Wnt signaling or Lhx1 expression.
苗勒管发育形成女性生殖器官，如输卵管和子宫。在妊娠期间，生成男性生殖器官和肾脏的沃尔夫管形成，随后苗勒管沿着预先形成的沃尔夫管向尾端延伸。对鸡胚中这两条管道进行解剖分离显示，沃尔夫管是苗勒管形成所必需的。同样，一些报告在小鼠中也支持了这一观点，包括对Wnt9b突变小鼠和沃尔夫管特异性Lhx1缺失的研究。然而，在小鼠中尚未建立沃尔夫管的解剖学消融方法。在本研究中，我们通过构建在沃尔夫管中特异性表达白喉毒素亚基的小鼠，探讨了这两条生殖管道之间相互作用的重要性。虽然这种对沃尔夫管的基因消融导致雄性和雌性突变小鼠均出现肾发育不全/肾缺如，但雌性突变小鼠缺乏源自苗勒管的子宫。在妊娠中期，苗勒管在突变的沃尔夫管过早终止的水平处截断，这意味着苗勒管的延伸依赖于预先形成的沃尔夫管。然而，突变小鼠中沃尔夫管中的Wnt9b表达及由此产生的经典Wnt活性，以及Lhx1表达均未受到影响。这些结果表明，沃尔夫管通过目前尚未明确的机制调节苗勒管的延伸，这些机制独立于经典Wnt信号传导或Lhx1表达。
