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Wt1 functions in ovarian follicle development by regulating granulosa cell differentiation.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2014 Jan 15; Vol. 23 (2), pp. 333-41. Date of Electronic Publication: 2013 Sep 05. - Publication Year :
- 2014
-
Abstract
- The Wt1 gene encodes a nuclear transcription factor that is specifically expressed in ovarian granulosa cells. However, the physiological significance of Wt1 in ovarian follicle development remains elusive. In this study, we found that Wt1(+/R394W) mice were grossly normal, however, the females displayed severe reproductive defects. Only ∼15% of the Wt1(+/R394W) females became pregnant after mating with wild-type males, compared with 88.2% of control females. Further study revealed that the subfertility of Wt1(+/R394W) females was caused by aberrant ovarian follicle development. Compared with control females, the ovary size and the number of developing follicles was significantly decreased in Wt1 mutant ovaries which was very similar to premature ovarian failure (POF) in human patients. The results of in vitro studies demonstrated that the expression of follicle stimulating hormone receptor (FSHR), 3β-hydroxysteroid dehydrogenase and Aromatase was inhibited by Wt1 in granulosa cells, and mutation of Wt1 resulted in the upregulation of these genes and in the premature differentiation of granulosa cells. We also found that Wt1 was likely involved in granulosa cell development via the regulation of E-cadherin and Par6b expression. Mutation in Wt1 caused defects in polarity establishment in granulosa cells, which also likely contributed to the observed aberrant follicle development. The results of this study provide new mechanisms for understanding the regulation of ovarian follicle development and potential pathological cause of POF in human patients.
- Subjects :
- 3-Hydroxysteroid Dehydrogenases metabolism
Adaptor Proteins, Signal Transducing metabolism
Animals
Aromatase metabolism
Cadherins metabolism
Cell Differentiation
Cell Polarity
Female
Fertility
Gene Expression Regulation
Granulosa Cells pathology
Humans
Male
Mice
Ovarian Follicle pathology
Ovulation
Pregnancy
Primary Ovarian Insufficiency pathology
Receptors, FSH metabolism
WT1 Proteins genetics
Granulosa Cells cytology
Granulosa Cells metabolism
Ovarian Follicle physiology
WT1 Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 24009315
- Full Text :
- https://doi.org/10.1093/hmg/ddt423