Mechanistic Drivers of Müllerian Duct Development and Differentiation Into the Oviduct.
Mechanistic Drivers of Müllerian Duct Development and Differentiation Into the Oviduct.
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DOI：
10.3389/fcell.2021.605301
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ahmed AA
中科院分区：
文献类型：
--
作者：
Santana Gonzalez L;Rota IA;Artibani M;Morotti M;Hu Z;Wietek N;Alsaadi A;Albukhari A;Sauka-Spengler T;Ahmed AA
生命的管道；动物的输卵管和人类的输卵管对于羊膜动物的生殖是至关重要的。它们连接卵巢和子宫，对生育至关重要。它们为配子维持、受精和着床前胚胎发育提供了适宜的环境。然而，严重的病理，如异位妊娠，恶性肿瘤和严重的感染，发生在输卵管。它们会对生育能力产生巨大影响，有些甚至会危及生命。尽管输卵管在生命中起着至关重要的作用，但人们对其前体结构<s:1>勒氏管的胚胎发育及其连续分化和成熟的分子驱动机制知之甚少。胆管是由上皮管腔和间质层组成的简单的初级管。它们分化为大多数成年女性生殖道（FRT）。<s:1>勒氏管形成的最早征象是前中肾体腔上皮增厚，形成两个不同祖细胞的基板。我们提出祖细胞的一个亚群经历部分上皮-间充质转化（pEMT），分化为未成熟的<s:1>勒氏管腔细胞，另一个亚群经历完全的上皮-间充质转化成为<s:1>勒氏间充质细胞。这些细胞内陷并增殖形成<s:1>勒氏管。随后，pEMT将被逆转，生成分化的上皮细胞，内衬完全形成的<s:1>勒氏管腔。前门管上皮细胞进一步分化为输卵管上皮亚型。本文综述了<s:1>勒氏管发育及其上段向输卵管分化过程的关键分子和遗传决定因素。此外，还对显示<s:1>勒氏型或输卵管表型的小鼠基因敲除系进行了广泛的全基因组调查。除了广泛确定的<s:1>勒氏管发育的遗传决定因素外，我们的研究还发现了几个基因的功能丧失与<s:1>勒氏管和/或输卵管的高外显率异常之间的惊人关联。值得注意的是，这些关联并没有得到详细的调查。最后，讨论了今后<s:1>勒管发展和导管的研究方向。
The conduits of life; the animal oviducts and human fallopian tubes are of paramount importance for reproduction in amniotes. They connect the ovary with the uterus and are essential for fertility. They provide the appropriate environment for gamete maintenance, fertilization and preimplantation embryonic development. However, serious pathologies, such as ectopic pregnancy, malignancy and severe infections, occur in the oviducts. They can have drastic effects on fertility, and some are life-threatening. Despite the crucial importance of the oviducts in life, relatively little is known about the molecular drivers underpinning the embryonic development of their precursor structures, the Müllerian ducts, and their successive differentiation and maturation. The Müllerian ducts are simple rudimentary tubes comprised of an epithelial lumen surrounded by a mesenchymal layer. They differentiate into most of the adult female reproductive tract (FRT). The earliest sign of Müllerian duct formation is the thickening of the anterior mesonephric coelomic epithelium to form a placode of two distinct progenitor cells. It is proposed that one subset of progenitor cells undergoes partial epithelial-mesenchymal transition (pEMT), differentiating into immature Müllerian luminal cells, and another subset undergoes complete EMT to become Müllerian mesenchymal cells. These cells invaginate and proliferate forming the Müllerian ducts. Subsequently, pEMT would be reversed to generate differentiated epithelial cells lining the fully formed Müllerian lumen. The anterior Müllerian epithelial cells further specialize into the oviduct epithelial subtypes. This review highlights the key established molecular and genetic determinants of the processes involved in Müllerian duct development and the differentiation of its upper segment into oviducts. Furthermore, an extensive genome-wide survey of mouse knockout lines displaying Müllerian or oviduct phenotypes was undertaken. In addition to widely established genetic determinants of Müllerian duct development, our search has identified surprising associations between loss-of-function of several genes and high-penetrance abnormalities in the Müllerian duct and/or oviducts. Remarkably, these associations have not been investigated in any detail. Finally, we discuss future directions for research on Müllerian duct development and oviducts.
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影响因子：
11.8
作者：
Carroll, TJ;Park, JS;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
9.8
作者：
De Tomasi, Lara;David, Pierre;Jeanpierre, Cecile
通讯作者：
Jeanpierre, Cecile
影响因子：
4
作者：
Chang, Xinyue;Qin, Yingying;Chen, Zi-Jiang
通讯作者：
Chen, Zi-Jiang
影响因子：
3.3
作者：
Brophy, Patrick D.;Rasmussen, Maria;Manak, J. Robert
通讯作者：
Manak, J. Robert
影响因子：
2.7
作者：
Ayers, K. L.;Cutting, A. D.;Smith, C. A.
通讯作者：
Smith, C. A.