Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.
Department of Developmental Genetics, Wakayama Medical University, Kimiidera 811-1, Wakayama City, Wakayama 641-8509, Japan.
Int J Mol Sci. 2021 Jan 26;22(3):1211. doi: 10.3390/ijms22031211.
The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.
沃尔夫管（WDs）和缪勒管（MDs）。大多数女性生殖管道（FRT）包括输卵管、子宫角和子宫颈都来源于 MDs。人们普遍认为 MDs 的形成依赖于尿生殖原基内预先形成的 WDs。在这里，我们发现 Hedgehog（Hh）信号调节下的 WD 间充质与胚胎期和出生后时期 FRT 的发育过程密切相关。Sonic hedgehog（Shh）的缺失，即唯一在 WDs 中特异性表达的 Hh 配体，阻止了 MD 间充质沿着径向轴影响子宫生长。体内细胞追踪方法表明，WD 退化后，对 WD 衍生的 Hh 信号有反应的特定细胞继续存在于发育中的 FRT 中，并逐渐有助于形成各种组织，如平滑肌、子宫内膜基质和血管，在小鼠子宫中。因此，我们的研究提供了一个依赖 WD 的 FRT 新的发育机制。
