The development of the Müllerian ducts into the female reproductive tract requires the coordination of multiple signaling pathways that regulate proliferation, apoptosis and differentiation. The Hippo pathway has been reported to interact with several pathways with established roles in Müllerian duct development, yet its potential roles in reproductive tract development and function remain mostly uncharacterized. The objective of this study was therefore to characterize the roles of the Hippo transcriptional coactivators YAP and TAZ in the female reproductive tract using transgenic mouse models. This report shows that the concomitant conditional inactivation of Yap and Taz in the mouse Müllerian duct mesenchyme results in postnatal developmental defects of the oviduct. Most notably, discontinuities in the myosalpinx layer lead to the progressive formation of cystic dilations of the isthmus. These defects prevented embryo transport and subsequent implantation in older animals, causing infertility. The loss of YAP/TAZ did not appear to affect other biological processes known to be required for the maintenance of oviductal wall integrity, such as TGF-β/SMAD and Notch signaling and the biogenesis of microRNAs, suggesting that the Hippo pathway acts independently of these processes to direct oviduct development. Taken together, these results suggest redundant and essential roles for YAP and TAZ in the postnatal development of the oviduct and the maintenance of its structural integrity.

中文翻译：

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YAP 和 TAZ 是出生后发育和维持输卵管结构完整性所必需的

苗勒管向女性生殖道的发育需要调节增殖、凋亡和分化的多种信号通路的协调。据报道，Hippo 通路与几种在苗勒管发育中具有既定作用的通路相互作用，但其在生殖道发育和功能中的潜在作用仍然大多未表征。因此，本研究的目的是使用转基因小鼠模型表征 Hippo 转录共激活因子 YAP 和 TAZ 在雌性生殖道中的作用。该报告显示，小鼠苗勒管间充质中 Yap 和 Taz 的伴随条件失活导致输卵管的出生后发育缺陷。最为显着地，输卵管层的不连续性导致峡部囊性扩张的逐渐形成。这些缺陷阻碍了老年动物的胚胎运输和随后的植入，从而导致不育。YAP/TAZ 的缺失似乎不影响其他已知维持输卵管壁完整性所需的生物过程，例如 TGF-β/SMAD 和 Notch 信号传导以及 microRNA 的生物发生，这表明 Hippo 通路的作用独立于这些过程指导输卵管发育。综上所述，这些结果表明 YAP 和 TAZ 在输卵管的出生后发育及其结构完整性的维护中发挥着多余和重要的作用。导致不孕。YAP/TAZ 的缺失似乎不会影响其他已知维持输卵管壁完整性所需的生物过程，例如 TGF-β/SMAD 和 Notch 信号传导以及 microRNA 的生物发生，这表明 Hippo 通路的作用独立于这些过程指导输卵管发育。综上所述，这些结果表明 YAP 和 TAZ 在输卵管的出生后发育及其结构完整性的维护中发挥着多余和重要的作用。导致不孕。YAP/TAZ 的缺失似乎不会影响其他已知维持输卵管壁完整性所需的生物过程，例如 TGF-β/SMAD 和 Notch 信号传导以及 microRNA 的生物发生，这表明 Hippo 通路的作用独立于这些过程指导输卵管发育。综上所述，这些结果表明 YAP 和 TAZ 在输卵管的出生后发育及其结构完整性的维护中发挥着多余和重要的作用。