INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Loss of GATA-6 and GATA-4 in Granulosa Cells Blocks Folliculogenesis, Ovulation, and Follicle Stimulating Hormone Receptor Expression Leading to Female Infertility

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/10562

Files in this item

File Description Format
PDF 2474.full.pdf (2MB) Main Article PDF
Title: Loss of GATA-6 and GATA-4 in Granulosa Cells Blocks Folliculogenesis, Ovulation, and Follicle Stimulating Hormone Receptor Expression Leading to Female Infertility
Author(s): Bennett, Jill; Wu, Yan-Guang; Gossen, Jan; Zhou, Ping; Stocco, Carlos
Abstract: Single GATA-6 (G6gcko), GATA-4 (G4gcko), and double GATA-4/6 (G4/6gcko) granulosa cell-specific knockout mice were generated to further investigate the role of GATA transcription factors in ovarian function in vivo. No reproductive defects were found in G6gcko animals. G4gcko animals were subfertile as indicated by the reduced number of pups per litter and the release of significantly fewer oocytes at ovulation. In marked contrast, G4/6gcko females fail to ovulate and are infertile. Furthermore, G4/6gcko females had irregular estrous cycles, which correlate with the abnormal ovarian histology found in unstimulated adult G4/6gcko females showing lack of follicular development and increased follicular atresia. Moreover, treatment with exogenous gonadotropins did not rescue folliculogenesis or ovulation in double-knockout G4/6gcko mice. In addition, ovary weight and estradiol levels were significantly reduced in G4gcko and G4/6gcko animals when compared with control and G6gcko mice. Aromatase, P450scc, and LH receptor expression was significantly lower in G4gcko and G4/6gcko mice when compared with control animals. Most prominently, FSH receptor (FSHR) protein was undetectable in granulosa cells of G4gcko and G4/6gcko. Accordingly, gel shift and reporter assays revealed that GATA-4 binds and stimulates the activity of the FSHR promoter. These results demonstrate that GATA-4 and GATA-6 are needed for normal ovarian function. Our data are consistent with a role for GATA-4 in the regulation of the FSHR gene and provide a possible molecular mechanism to explain the fertility defects observed in animals with deficient GATA expression in the ovary.
Issue Date: 2012-05
Publisher: Endocrine Society
Citation Info: Bennett, J. Wu, Y. G. Gossen, J. Zhou, P. Stocco, C.. (2012). "Loss of GATA-6 and GATA-4 in Granulosa Cells Blocks Folliculogenesis, Ovulation, and Follicle Stimulating Hormone Receptor Expression Leading to Female Infertility." Endocrinology. 2012 May;153(5):2474-85 doi: 10.1210/en.2011-1969
Type: Article
Description: This is a copy of an article published in Endocrinology © 2012 Endocrine Society. endo.endojournals.org/ doi: 10.1210/en.2011-1969
URI: http://hdl.handle.net/10027/10562
ISSN: 0013-7227
Sponsor: National Institutes of Health Grants R01HD057110 and R21HD066233. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/ National Institutes of Health (SCCPIR) Grant U54-HD28934.
Date Available in INDIGO: 2013-11-19
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 242
China 131
Russian Federation 24
United Kingdom 11
Ukraine 11

Browse

My Account

Information

Access Key