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Developmental Programming: Adipose Depot-Specific Transcriptional Regulation by Prenatal Testosterone Excess in a Sheep Model of PCOS

ABSTRACT: Developmental Programming: Adipose Depot-Specific Transcriptional Regulation by Prenatal Testosterone Excess in a Sheep Model of PCOS

PROVIDER: PRJNA665223 | ENA |

REPOSITORIES: ENA

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Developmental Programming: Adipose Depot-Specific Transcriptional Regulation by Prenatal Testosterone Excess in a Sheep Model of PCOS

Project description:This study seeks to undertake an assessment of the effects of prenatal exposure of female sheep to excess testosterone, the estrogen precursor, in four different adipose depots. The depots investigated are subcutaneous adipose tissue (SAT) - a fat beneath the skin storing >80% of total body fat in the human body, visceral adipose tissue (VAT) - an intra-abdominal fat primarily associated with digestive system organs, and smaller depots such as epicardial adipose tissue (ECAT) and perirenal adipose tissue (PRAT) that serve specialized functions associated with the organs/tissues in their proximity. The goals are to 1) determine gene expression and gene network profiles in the depots; 2) assess prenatal T-treatment induced disruptions in adipose depot-specific gene expression and gene networks; and 3) identify common and divergent gene and gene pathways underlying depot-specific disruption in prenatal T-treated female sheep.

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Developmental Programming: adipose depot-specific regulation of non-coding RNAs and their relation to coding RNA expression in prenatal testosterone and prenatal bisphenol-A -treated female sheep

Project description:Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female sheep. Adipocytes are key regulators of insulin sensitivity and tissue-specific differences in insulin sensitivity, coupled with adipose depot-specific changes in key mRNAs, were previously observed. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) regulators of gene expression would prevail to account for the direction of changes seen in mRNAs. Noncoding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific that were mutually exclusive suggestive of different regulatory entry points in this regulation.

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Developmental Programming: Sheep Granulosa and Theca Cell-Specific Transcriptional Regulation by Prenatal Testosterone

Project description:Prenatal testosterone treated sheep, similar to PCOS women, manifest reduced cyclicity, functional hyperandrogenism and polycystic ovary (PCO) morphology. The PCO morphology results from increased follicular recruitment and persistence of antral follicles, consequence of reduced follicular growth and atresia, and driven by cell-specific gene expression changes that are poorly understood. Therefore, utilizing RNA sequencing, cell-specific transcriptional changes were assessed in laser capture microdissection isolated antral follicular granulosa and theca cells from 21 months-of- age control and prenatal testosterone treated sheep.

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Prenatal programming: adverse cardiac programming by gestational testosterone excess.

Project description: Not available

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Gene regulatory activity associated with PCOS reveals DENND1A-dependent testosterone production

Project description:Polycystic Ovary Syndrome (PCOS) is a leading cause of infertility. About 5 million women in the US have PCOS, making it the most prevalent endocrine disorder among menstruating people. Despite that prevalence, the underlying causes remain unknown. Genome-wide association studies (GWAS) have identified non-coding genetic variation associated with PCOS risk and identifying the underlying molecular mechanisms is currently a major opportunity for improving diagnosis and treatment. We report the discovery of gene regulatory mechanisms that help explain genetic association with PCOS in the GATA4, FSHB and DENND1A loci. We based those findings using a combination of high throughput reporter assays, CRISPR-based epigenome editing, and genetic association analysis from PCOS case and control populations. In addition, we found that elevated endogenous DENND1A expression causes elevated testosterone levels, a hallmark PCOS phenotype. These results further highlight the potential for combining genetic variant analyses with experimental approaches to fine map genetic associations with disease risk.

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Developmental programming: differential effects of prenatal testosterone excess on insulin target tissues.

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Developmental Programming: Impact of prenatal testosterone excess on liver and muscle transcriptome and the relationship between non-coding and coding RNA networks in female sheep [ncRNA-seq]

Project description:This study seeks to assess the effects of prenatal exposure of female sheep to execessive testosterone in metabolically relevant liver and muscle tissue. The goals are to 1) determine noncoding RNA in the control animals and 2) assess the effects of prenatal T-treatment on non-coding RNA. 3) Finally identify putative ncRNA-totalRNA interactions.

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Developmental Programming: Impact of prenatal testosterone excess on liver and muscle transcriptome and the relationship between non-coding and coding RNA networks in female sheep [RNA-seq]

Project description:This study seeks to assess the effects of prenatal exposure of female sheep to execessive testosterone in metabolically relevant liver and muscle tissue. The goals are to 1) determine genes and gene pathways in the control animals and 2) assess the effects of prenatal T-treatment on gene expression and gene pathways. 3) Finally identify putative ncRNA-totalRNA interactions.

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miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS

Project description:To reveal microRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Affymetrix miRNA 2.0. Six pooled RNAs from CC samples (three PCOS and three non-PCOS pooled RNAs) were separately analyzed on 6 GeneChip miRNA 2.0 Array (miRBase V15)

2015-04-28 | E-GEOD-68285 | biostudies-arrayexpress

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