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Connective tissue growth factor is required for normal follicle development and ovulation.
- Source :
-
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2011 Oct; Vol. 25 (10), pp. 1740-59. Date of Electronic Publication: 2011 Aug 25. - Publication Year :
- 2011
-
Abstract
- Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis and secretion of which are hypothesized to be selectively regulated by activins and other members of the TGF-β superfamily. To investigate the in vivo roles of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple reproductive defects including disrupted follicle development, decreased ovulation rates, increased numbers of corpus luteum, and smaller but functionally normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading to increased levels of serum progesterone. We show that disrupted follicle development is accompanied by a significant increase in granulosa cell apoptosis. Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant decrease in oocytes ovulated, likely due to impaired ovulatory process. During analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show gene expression changes similar to our previously reported granulosa cell-specific knockouts of activin and Smad4, the common TGF-β family intracellular signaling protein. We also discovered a significant down-regulation of Adamts1, a progesterone-regulated gene that is critical for the remodeling of extracellular matrix surrounding granulosa cells of preovulatory follicles. These findings demonstrate that CTGF is a downstream mediator in TGF-β and progesterone signaling cascades and is necessary for normal follicle development and ovulation.
- Subjects :
- ADAM Proteins genetics
ADAM Proteins metabolism
ADAMTS1 Protein
Animals
Apoptosis
Connective Tissue Growth Factor deficiency
Connective Tissue Growth Factor genetics
Corpus Luteum growth & development
Corpus Luteum metabolism
Corpus Luteum pathology
Cumulus Cells metabolism
Cumulus Cells pathology
Decidua metabolism
Decidua pathology
Female
Gene Deletion
Gene Expression Regulation, Developmental
Infertility, Female blood
Infertility, Female metabolism
Infertility, Female pathology
Mice
Mice, Knockout
Models, Biological
Ovarian Follicle metabolism
Ovarian Follicle pathology
Progesterone blood
RNA, Messenger genetics
RNA, Messenger metabolism
Real-Time Polymerase Chain Reaction
Recombination, Genetic genetics
Time Factors
Connective Tissue Growth Factor metabolism
Ovarian Follicle growth & development
Ovulation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1944-9917
- Volume :
- 25
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular endocrinology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 21868453
- Full Text :
- https://doi.org/10.1210/me.2011-1045