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

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.

2015 ◽  
Vol 25 (6) ◽  
pp. 1059-1073 ◽  
Author(s):  
Renata Prunskaite-Hyyryläinen ◽  
Ilya Skovorodkin ◽  
Qi Xu ◽  
Ilkka Miinalainen ◽  
Jingdong Shan ◽  
...  

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Malcolm M Moses ◽  
Richard R Behringer

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.


2017 ◽  
Author(s):  
Rachel D. Mullen ◽  
Ying Wang ◽  
Bin Liu ◽  
Emma L. Moore ◽  
Richard R. Behringer

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.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1416
Author(s):  
Qiuping Liu ◽  
Xiaomeng Liu ◽  
Guanbin Song

The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers. Its biological significance and deregulation in cancer have drawn increasing interest in the past few years. A fundamental understanding of the complexity of the Hippo pathway in cancer is crucial for improving future clinical interventions and therapy for cancers. In this review, we try to clarify the complex regulation and function of the Hippo signaling network in cancer development, including its role in signal transduction, metabolic regulation, and tumor development, as well as tumor therapies targeting the Hippo pathway.


2018 ◽  
Vol 19 (12) ◽  
pp. 4097 ◽  
Author(s):  
Karl Kerns ◽  
Michal Zigo ◽  
Peter Sutovsky

The importance of zinc for male fertility only emerged recently, being propelled in part by consumer interest in nutritional supplements containing ionic trace minerals. Here, we review the properties, biological roles and cellular mechanisms that are relevant to zinc function in the male reproductive system, survey available peer-reviewed data on nutritional zinc supplementation for fertility improvement in livestock animals and infertility therapy in men, and discuss the recently discovered signaling pathways involving zinc in sperm maturation and fertilization. Emphasis is on the zinc-interacting sperm proteome and its involvement in the regulation of sperm structure and function, from spermatogenesis and epididymal sperm maturation to sperm interactions with the female reproductive tract, capacitation, fertilization, and embryo development. Merits of dietary zinc supplementation and zinc inclusion into semen processing media are considered with livestock artificial insemination (AI) and human assisted reproductive therapy (ART) in mind. Collectively, the currently available data underline the importance of zinc ions for male fertility, which could be harnessed to improve human reproductive health and reproductive efficiency in agriculturally important livestock species. Further research will advance the field of sperm and fertilization biology, provide new research tools, and ultimately optimize semen processing procedures for human infertility therapy and livestock AI.


2004 ◽  
Vol 16 (4) ◽  
pp. 447 ◽  
Author(s):  
Lindsay Gillan ◽  
W. M. Chis Maxwell ◽  
Gareth Evans

Many years of research have been devoted to improving the fertility of preserved semen of small ruminants. There have been few significant advances in preservation in recent times, but considerable knowledge has been gained on the effect of preservation on the structure and function of spermatozoa. It has become evident that preservation greatly affects many sperm attributes, such as motility, respiratory activity, membrane status and DNA quality. Consequently, viability is reduced, transport in the female reproductive tract is inhibited, the timing of fertilisation is altered and embryo development is affected following insemination of preserved, compared to fresh spermatozoa. A greater understanding of their functional condition may lead to the development of methods of preventing these alterations or to improved methods of using the preserved spermatozoa for artificial insemination in their altered state.


2021 ◽  
Vol 17 ◽  
Author(s):  
Naina Kumar ◽  
Ashu Yadav

Aims: Present study was conducted to know presentations and nature of Müllerian-duct anomalies in rural women. Background: Müllerian anomalies are congenital defects of female reproductive tract resulting from faulty development and fusion of Müllerian ducts. Objectives: To identify common Müllerian anomalies, their presentation, radiological appearances, complications, associated renal anomalies in rural women of Northern India. Methods: Present observational study was conducted on 181 female patients with suspected Müllerian anomalies presenting to the outpatient department of Obstetrics and Gynecology with various complaints. Data included age, religion, menarche, previous pregnancy if any, duration of infertility, presenting complaints, type of Müllerian anomaly, incidental or symptomatic, diagnostic method, associated anomalies. Statistical analysis was done using SPSS 22.0 version software. Results: Of 181 patients, 16.5% were adolescents, 83.5% adult women with an overall mean (SD) age of 25.02 (5.96) years. Of these, 170 had true Müllerian-duct anomalies and 11 had defects other than Müllerian anomalies, hence excluded. Total 158(92.9%) patients were symptomatic and 12(7.1%) asymptomatic at presentation. The majority (75.9%) were diagnosed incidentally during their visit to the department for various complaints of which infertility (32.4%) was most common. Septate uterus (29.4%) was most common anomaly diagnosed followed by Müllerian agenesis/hypoplasia (22.9%). Around 11.2% cases had associated renal and collecting system anomalies with unilateral renal agenesis (47.4%) being most common. Conclusion: Hence, Müllerian-duct anomalies have diverse presentations and most of them are diagnosed incidentally. Other: The exact prevalence of Müllerian-duct anomalies may be high, especially in rural India due to lack of knowledge and societal pressures.


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