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ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 2018 Oct 15; Vol. 474, pp. 214-226. Date of Electronic Publication: 2018 Mar 24. - Publication Year :
- 2018
-
Abstract
- Estrogen receptor 2 (ESR2) plays a critical role in folliculogenesis and ovulation. Disruption of ESR2-function in the rats results in female infertility due to failure of ovulation. Ovulation failure occurred in two distinct rat models, a null mutant and a DNA binding domain (DBD) mutant of ESR2, indicating that transcriptional regulation by ESR2 is indispensable for ovulation. To define the regulatory role of ESR2 in preovulatory follicular maturation and ovulation, we investigated ovarian responsiveness to exogenous gonadotropins in prepubertal females. Granulosa cells (GCs) play a vital role in follicle maturation and ovulation, and ESR2-dependent estrogen signaling is predominant in GCs, therefore, we examined the differential expression of gonadotropin-induced genes in GCs. Of 32,623 genes detected by RNA-sequencing, 1696 were differentially expressed in Esr2-mutant rats (789 downregulated, and 907 upregulated, absolute fold change 2, FDR p < 0.05). Molecular pathway analyses indicated that these differentially expressed genes are involved in steroidogenesis, follicle maturation, and ovulation. Many of these genes are known regulators of ovarian function and a subset were also disrupted in Esr2-mutant mice. Interestingly, Kiss1 was identified as one of the differentially expressed genes implicating a potential role within the follicle and its regulation by ESR2. Our findings indicate that ESR2 regulates key genes in GCs that are essential for follicle maturation and ovulation in the rat.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Estrogen Receptor beta genetics
Female
Fertility genetics
Gene Expression Profiling
Gonadotropins pharmacology
Mutation genetics
Rats, Sprague-Dawley
Reproducibility of Results
Signal Transduction drug effects
Signal Transduction genetics
Cell Differentiation genetics
Estrogen Receptor beta metabolism
Gene Expression Regulation
Granulosa Cells cytology
Granulosa Cells metabolism
Ovulation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8057
- Volume :
- 474
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 29580824
- Full Text :
- https://doi.org/10.1016/j.mce.2018.03.012