scholarly journals A gene regulatory network for Müllerian duct regression

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Malcolm M Moses ◽  
Richard R Behringer
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Reproductive Tract ◽  
Sex Differentiation ◽  
Female Reproductive Tract ◽  
Mullerian Duct ◽  
Male And Female ◽  
Müllerian Duct ◽  
New Genes ◽  
Gene Regulatory

Abstract Mammalian embryos initially develop progenitor tissues for both male and female reproductive tract organs, known as the Wolffian ducts and the Müllerian ducts, respectively. Ultimately, each individual develops a single set of male or female reproductive tract organs. Therefore, an essential step for sex differentiation is the regression of one duct and growth and differentiation of the other duct. In males, this requires Müllerian duct regression and Wolffian duct growth and differentiation. Müllerian duct regression is induced by the expression of Amh, encoding anti-Müllerian hormone, from the fetal testes. Subsequently, receptor-mediated signal transduction in mesenchymal cells surrounding the Müllerian duct epithelium leads to duct elimination. The genes that induce Amh transcription and the downstream signaling that results from Amh activity form a pathway. However, the molecular details of this pathway are currently unknown. A set of essential genes for AMH pathway function has been identified. More recently, transcriptome analysis of male and female Müllerian duct mesenchyme at an initial stage of regression has identified new genes that may mediate elimination of the Müllerian system. The evidence taken together can be used to generate an initial gene regulatory network describing the Amh pathway for Müllerian duct regression. An Amh gene regulatory network will be a useful tool to study Müllerian duct regression, sex differentiation, and its relationship to environmental influences.

scholarly journals Osterix functions downstream of anti-Müllerian hormone signaling to regulate Müllerian duct regression

2017 ◽  
Author(s):  
Rachel D. Mullen ◽  
Ying Wang ◽  
Bin Liu ◽  
Emma L. Moore ◽  
Richard R. Behringer
Keyword(s):  
Transforming Growth Factor Beta ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Mesenchymal Cells ◽  
Female Reproductive Tract ◽  
Mullerian Duct ◽  
Male And Female ◽  
Müllerian Duct

AbstractIn mammals, the developing reproductive tract primordium of male and female fetuses consists of the Wolffian duct and the Müllerian duct (MD), two epithelial tube pairs surrounded by mesenchyme. During male development, mesenchyme-epithelia interactions mediate MD regression to prevent its development into a uterus, oviduct and upper vagina. It is well established that transforming growth factor-beta family member anti-Müllerian hormone (AMH) secreted from the fetal testis and its type 1 and 2 receptors expressed in MD mesenchyme regulate MD regression. However, little is known about the molecular network regulating downstream actions of AMH signaling. To identify potential AMH-induced genes and regulatory networks controlling MD regression in a global non-biased manner, we examined transcriptome differences in MD mesenchyme between males (AMH signaling on) and females (AMH signaling off) by RNA-Seq analysis of purified fetal MD mesenchymal cells. This analysis found 82 genes up-regulated in males during MD regression and identified Osterix (Osx)/Sp7, a key transcriptional regulator of osteoblast differentiation and bone formation, as a novel downstream effector of AMH signaling during MD regression. Osx/OSX was expressed in a male-specific pattern in MD mesenchyme during MD regression. OSX expression was lost in mutant males without AMH signaling. In addition, transgenic mice ectopically expressing human AMH in females induced a male pattern of Osx expression. Together these results indicate that AMH signaling is necessary and sufficient for Osx expression in the MD mesenchyme. In addition, MD regression was delayed in Osx null males, identifying Osx as a new factor that regulates MD regression.SignificanceIn mammals, each embryo forms both male and female reproductive tract organ progenitor tissues. Anti-Müllerian hormone (AMH) secreted by fetal testes acts on mesenchyme cells adjacent to the Müllerian duct (MD) epithelium, the progenitor tissue of the female reproductive tract, to induce MD regression. While AMH and early AMH signaling components are elucidated, downstream gene networks directing this process are largely unknown. A global non-biased approach using whole transcriptome sequencing of fetal MD mesenchymal cells identified 82 factors as potential target genes of AMH including Osterix (Osx). Our findings provide in vivo evidence Osx is an AMH-induced gene that regulates MD regression. Identification of Osx may provide key insights into gene regulatory networks underlying MD regression and male sex differentiation.

scholarly journals Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract

2015 ◽  
Vol 25 (6) ◽  
pp. 1059-1073 ◽  
Author(s):  
Renata Prunskaite-Hyyryläinen ◽  
Ilya Skovorodkin ◽  
Qi Xu ◽  
Ilkka Miinalainen ◽  
Jingdong Shan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Mullerian Duct ◽  
Müllerian Duct ◽  
Directional Cell Migration

scholarly journals YAP and TAZ are required for the postnatal development and the maintenance of the structural integrity of the oviduct

Reproduction ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 307-318
Author(s):  
Philippe Godin ◽  
Mayra Tsoi ◽  
Marilène Paquet ◽  
Derek Boerboom
Keyword(s):  
Postnatal Development ◽  
Reproductive Tract ◽  
Structural Integrity ◽  
Hippo Pathway ◽  
Female Reproductive Tract ◽  
Mullerian Duct ◽  
Developmental Defects ◽  
Müllerian Duct ◽  
And Function ◽  
The Hippo Pathway

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 miRNA, 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.

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