Document Detail


Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis.
MedLine Citation:
PMID:  23288785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A significant number of patients with germline mutations in the Wilms' tumour 1 (WT1) gene, a transcriptional factor essential for early renal and gonadal development, display cryptorchidism or non-scrotal testis position. We show here that WT1 is expressed during development in the mouse gubernacular ligament connecting the testis to the abdominal wall. Conditional inactivation of Wt1 in the gubernaculum (GU-WT1KO animals) resulted in abnormal differentiation of the gubernacula during development and, in about 40% of adult males, unilateral, always left-sided, cryptorchidism. At birth the right testis was positioned above the processus vaginalis and eventually moved into the developing scrotal pouch. In affected mutants the left testis was displaced from the normal position and the left processus vaginalis failed to form. The analysis of testicular descent at different stages of postnatal development suggests that unilateral cryptorchidism might be caused by asymmetry in the positions of the abdominal organs providing a higher degree of mobility for the left testis. Spermatogenesis in GU-WT1KO animals was blocked in cryptorchid testes located in a high pararenal position, but was maintained in testes located in a low abdominal position. Conditional inactivation of both Wt1 and androgen receptor (Ar) genes in the gubernaculum led to a bilateral asymmetrical cryptorchidism in all mutant males, with the left testis again located higher than the right one. The malformations induced by WT1 and AR deficiency in the gubernaculum and processus vaginalis, in combination with mechanical constraints on testis descent, determine the final position of the testes. In summary, our data indicate that WT1 is directly involved in gubernaculum differentiation. Taken together, the results of the study underline the complex nature of testicular descent, with an involvement in this process of several genetic factors and developmental events.
Authors:
Elena M Kaftanovskaya; Giselle Neukirchner; Vicki Huff; Alexander I Agoulnik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-12
Journal Detail:
Title:  The Journal of pathology     Volume:  230     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-13     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  39-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cryptorchidism / genetics*
Female
Flow Cytometry
Gene Deletion
Gene Expression Regulation, Developmental / physiology*
Inguinal Canal / growth & development,  physiology
Kidney / growth & development,  physiology
Lac Operon
Male
Mice
Mice, Knockout
Receptors, Androgen / genetics
Testis / abnormalities*,  growth & development,  physiology*
WT1 Proteins / genetics*
Grant Support
ID/Acronym/Agency:
CA34936/CA/NCI NIH HHS; R01 HD037067/HD/NICHD NIH HHS; R01HD37067/HD/NICHD NIH HHS; R25 GM061347/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Androgen; 0/WT1 Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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