New Insights into Development of Female Reproductive Tract-Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development.

Ryuma Haraguchi,Aki Murashima,Riko Kitazawa,Gen Yamada,Sohei Kitazawa,Daisuke Matsumaru

doi:10.3390/ijms22031211

Abstract

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.

Highlights

The female reproductive tract (FRT) originates from the Mullerian ducts (MDs) that contribute to the formation of the oviducts, uterine horn and cervix [1,2,3]
Sonic hedgehog (Shh) mRNA was detected in the Wolffian ducts (WDs) epithelium (Figure 1A), as described in previous studies [15,16]
Hhsignal-responding progenitors located in the mesenchyme surrounding WD can contribute to distinct uterine components

Summary

Introduction

The female reproductive tract (FRT) originates from the Mullerian ducts (MDs) that contribute to the formation of the oviducts, uterine horn and cervix [1,2,3]. The formation of MDs depends on preformed Wolffian ducts (WDs) within the urogenital ridge [4,5]. Following WD formation, cells of the coelomic epithelium, a single layer of cells covering the entire body cavity, is specified to MD precursors by WD-derived inductive signals; MD precursors invaginate by linking with these canalizations and elongate caudally toward the urogenital sinus using WDs as “guide wires” [5]. Interactions between WDs and MDs are assumed to play roles in FRT formation because WDs localize close to the coelomic epithelium or MDs during embryogenesis. Wolffian-derived signals coupled with the BMP/Pax axis activate

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Conclusion