| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 19, 2005
Accepted on October 21, 2005
1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest
Research Centre for Reproductive Health, Department of Obstetrics and Gynaecology, University of Adelaide, SA 5005, Australia
* To whom correspondence should be addressed. E-mail: sarah.robertson{at}adelaide.edu.au.
Transforming growth factor 
1 (TGF1) is implicated in regulation of ovarian function and the events of early pregnancy. We have investigated the effect of null mutation in the Tgf1 gene on reproductive function in female mice. The reproductive capacity of TGF1 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 TGF1 null mutant mice failed to display the characteristic proestrus surge in circulating LH. Ovarian hyperstimulation with exogenous gonadotrophins elicited normal ovulation rates in TGF1 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 HSD31 and P450c17. Embryos recovered from TGF1 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 TGF1. We conclude that embryo arrest is due to developmental incompetence in oocytes developed in a TGF1 deficient follicular environment. This study demonstrates that TGF1 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.
1 •
ovary •
oocyte •
follicle •
embryo •
LH •
progesterone
This article has been cited by other articles:
 |
|
 |
|
  Y.-J. Chen, M.-T. Lee, H.-C. Yao, P.-W. Hsiao, F.-C. Ke, and J.-J. Hwang Crucial Role of Estrogen Receptor-{alpha} Interaction with Transcription Coregulators in Follicle-Stimulating Hormone and Transforming Growth Factor {beta}1 Up-Regulation of Steroidogenesis in Rat Ovarian Granulosa Cells Endocrinology, September 1, 2008; 149(9): 4658 - 4668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. V. Ingman and R. L. Jones Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of cytokines in reproductive biology Hum. Reprod. Update, March 1, 2008; 14(2): 179 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. V. Ingman and S. A. Robertson Transforming Growth Factor-{beta}1 Null Mutation Causes Infertility in Male Mice Associated with Testosterone Deficiency and Sexual Dysfunction Endocrinology, August 1, 2007; 148(8): 4032 - 4043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Diaz, K. Wigglesworth, and J. J. Eppig Oocytes determine cumulus cell lineage in mouse ovarian follicles J. Cell Sci., April 15, 2007; 120(8): 1330 - 1340. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
