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Characterization of the effects of Runx1 KO in the mouse adult ovary

ABSTRACT: In this study, we investigated the effects of Runx1 loss on ovarian pathogenesis in mice. Conditional loss of Runx1 in the somatic cells of the ovary led to an increased prevalence of ovarian tumors in aged mice. While ovaries from4.5 months old mice did not display tumors, they all contained abnormal follicle-like lesions. RNA-Sequencing analysis on 4.5 month old ovaries identified differentially expressed genes in Runx1 KO ovaries, including genes involved in metaplasia, ovarian cancer, epithelial cell development, tight junctions, cell-cell adhesion, and Wnt/beta-catenin pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE211241 | GEO | 2023/08/08

REPOSITORIES: GEO

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RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2

Project description:We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in various vertebrate species. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. To understand the function of Runx1 during fetal development of the ovary, we ablated Runx1 specifically in the somatic cell lineage of the fetal ovaries using Sf1-Cre . We compared ovarian differentiation in wild type, Runx1 and Foxl2 single knockouts, and Runx1/Foxl2 double knockout ovaries. Transcriptome comparisons of newborn ovaries revealed that loss of Runx1 or Foxl2 affected a similar set of genes: 41% of the genes affected by the loss of Runx1 were also changed by the loss of Foxl2. Despite these transcriptomic changes, granulosa cell identity was maintained during fetal life in both Runx1 or Foxl2 single knockout ovaries. However, the combined loss of Runx1/Foxl2 resulted in masculinization of the ovaries during fetal life. To further characterize the impacts of the combined loss of Runx1 and Foxl2 on ovarian differentiation, we compared the transcriptome of Runx1/Foxl2 DKO newborn ovaries with the transcriptomes of control, Runx1, or Foxl2 single KO ovaries.

2019-07-17 | GSE129038 | GEO

RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2

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Identification of genes regulated by long noncoding RNA H19 in the ovary.

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Arid1a deletion in collaboration with Pten deletion leads to ovarian tumorigenesis in mouse

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2011-11-15 | E-GEOD-21706 | biostudies-arrayexpress

Foxl2 functions in sex determination and histogenesis throughout mouse ovary development, analyzed by Agilent arrays

Project description:Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, i.e., Rspo1 and Wnt4. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit, to identify ovarian targets of Foxl2 that, along with some testis genes, were dysregulated during embryonic development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers. The results, including a comprehensive principal component analysis of published microarray datasets 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for a role in sex determination independent of FOXL2 (notably, the transcription factor, ZBTB7C) and in the generation of the ovarian reserve downstream of it (e.g., the cadherin-domain protein CLSTN2, or the sphingomyelin synthase, SGMS2). The gene inventory provides a framework to analyze the genetic bases of ovarian development and female fertility. Keywords: reference design Comparison of Foxl2+/+,+/- and -/- whole ovaries at 2 timepoints delineating follicle formation

2010-05-17 | E-GEOD-12942 | biostudies-arrayexpress

Arid1a deletion in collaboration with Pten deletion leads to ovarian tumorigenesis in mouse

2014-04-05 | GSE56531 | GEO

RNA Deep Sequencing Reveals Expression Patterns of Long Non-coding RNAs during Swine Ovary Development

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