Document Detail


Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest.
MedLine Citation:
PMID:  16269452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TGFbeta1 is implicated in regulation of ovarian function and the events of early pregnancy. We have investigated the effect of null mutation in the Tgfbeta1 gene on reproductive function in female mice. The reproductive capacity of TGFbeta1 null mutant females was severely impaired, leading to almost complete infertility. Onset of sexual maturity was delayed, after which ovarian function was disrupted, with extended ovarian cycles, irregular ovulation, and a 40% reduction in oocytes ovulated. Serum FSH and estrogen content were normal, but TGFbeta1 null mutant mice failed to display the characteristic proestrus surge in circulating LH. Ovarian hyperstimulation with exogenous gonadotropins elicited normal ovulation rates in TGFbeta1 null mutant mice. After mating with wild-type stud males, serum progesterone content was reduced by 75% associated with altered ovarian expression of mRNAs encoding steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase-1 and P450 17 alpha-hydroxylase/C17-20-lyase. Embryos recovered from TGFbeta1 null mutant females were developmentally arrested in the morula stage and rarely progressed to blastocysts. Attempts to rescue embryos by exogenous progesterone administration and in vitro culture were unsuccessful, and in vitro fertilization and culture experiments demonstrated that impaired development is unlikely to result from lack of maternal tract TGFbeta1. We conclude that embryo arrest is due to developmental incompetence in oocytes developed in a TGFbeta1-deficient follicular environment. This study demonstrates that TGFbeta1 is a critical determinant of normal ovarian function, operating through regulation of LH activity and generation of oocytes competent for embryonic development and successful initiation of pregnancy.
Authors:
Wendy V Ingman; Rebecca L Robker; Karen Woittiez; Sarah A Robertson
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-03
Journal Detail:
Title:  Endocrinology     Volume:  147     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-18     Completed Date:  2006-03-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  835-45     Citation Subset:  AIM; IM    
Affiliation:
Research Centre for Reproductive Health, Department of Obstetrics and Gynaecology, University of Adelaide, South Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Embryonic Development / physiology*
Estrous Cycle / physiology
Female
Infertility, Female / genetics,  metabolism*
Mice
Mice, Knockout
Mice, SCID
Mutation*
Ovary / metabolism
Ovulation / metabolism
Ovum / physiology
Pregnancy
Pregnancy, Animal / metabolism*
Progesterone / metabolism*
Sexual Maturation / genetics,  physiology*
Transforming Growth Factor beta / genetics*,  metabolism
Transforming Growth Factor beta1
Chemical
Reg. No./Substance:
0/Tgfb1 protein, mouse; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 57-83-0/Progesterone

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


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