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Estrogen-dependent gene expression in the mouse ovary.

ABSTRACT: Estrogen (E) plays a pivotal role in regulating the female reproductive system, particularly the ovary. However, the number and type of ovarian genes influenced by estrogen remain to be fully elucidated. In this study, we have utilized wild-type (WT) and aromatase knockout (ArKO; estrogen free) mouse ovaries as an in vivo model to profile estrogen dependent genes. RNA from each individual ovary (n?=?3) was analyzed by a microarray-based screen using Illumina Sentrix Mouse WG-6 BeadChip (45,281 transcripts). Comparative analysis (GeneSpring) showed differential expression profiles of 450 genes influenced by E, with 291 genes up-regulated and 159 down-regulated by 2-fold or greater in the ArKO ovary compared to WT. Genes previously reported to be E regulated in ArKO ovaries were confirmed, in addition to novel genes not previously reported to be expressed or regulated by E in the ovary. Of genes involved in 5 diverse functional processes (hormonal processes, reproduction, sex differentiation and determination, apoptosis and cellular processes) 78 had estrogen-responsive elements (ERE). These analyses define the transcriptome regulated by E in the mouse ovary. Further analysis and investigation will increase our knowledge pertaining to how E influences follicular development and other ovarian functions.

SUBMITTER: Liew SH

PROVIDER: S-EPMC3036593 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Estrogen-dependent gene expression in the mouse ovary.

Liew Seng H SH Sarraj Mai A MA Drummond Ann E AE Findlay Jock K JK

PloS one 20110209 2

Estrogen (E) plays a pivotal role in regulating the female reproductive system, particularly the ovary. However, the number and type of ovarian genes influenced by estrogen remain to be fully elucidated. In this study, we have utilized wild-type (WT) and aromatase knockout (ArKO; estrogen free) mouse ovaries as an in vivo model to profile estrogen dependent genes. RNA from each individual ovary (n = 3) was analyzed by a microarray-based screen using Illumina Sentrix Mouse WG-6 BeadChip (45,281 t ...[more]

PMID: 21347412

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Project description:Within the ovary, Estrogen Receptor ? (ER?) is localized to the granulosa cells of growing follicles. 17?-estradiol (E2) acting via ER? augments the actions of follicle stimulating hormone in granulosa cells, leading to granulosa cell differentiation and formation of a preovulatory follicle. Adult ER?-null females are subfertile and possess ovaries with reduced numbers of growing follicles and corpora lutea. Because the majority of E2 production by granulosa cells occurs once puberty is reached, a role for ER? in the ovary prior to puberty has not been well examined. We now provide evidence that lack of ER? disrupts gene expression as early as post-natal day (PND) 13, and in particular, we identify a number of genes of the extracellular matrix (ECM) that are significantly higher in ER?-null follicles than in wildtype (WT) follicles. Considerable changes occur to the ECM occur during normal folliculogenesis to allow for the dramatic growth, cellular differentiation, and reorganization of the follicle from the primary to preovulatory stage. Using quantitative PCR and immunofluorescence, we now show that several ECM genes are aberrantly overexpressed in ER?-null follicles. We find that Collagen11a1, a protein highly expressed in cartilage, is significantly higher in ER?-null follicles than WT follicles as early as PND 13, and this heightened expression continues through PND 23-29 into adulthood. Similarly, Nidogen 2, a highly conserved basement membrane glycoprotein, is elevated in ER?-null follicles at PND 13 into adulthood, and is elevated specifically in the ER?-null focimatrix, a basal lamina-like matrix located between granulosa cells. Focimatrix laminin and Collagen IV expression were also higher in ER?-null ovaries than in WT ovaries at various ages. Our findings suggest two novel observations: a) that ER? regulates granulosa cell gene expression ovary prior to puberty, and b) that ER? regulates expression of ECM components in the mouse ovary.

Dataset Information

Estrogen-dependent gene expression in the mouse ovary.

Publications

Estrogen-dependent gene expression in the mouse ovary.

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