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Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep

ABSTRACT: Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep

PROVIDER: PRJNA786645 | ENA |

REPOSITORIES: ENA

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Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [RNA-Seq]

Project description:Gestational Bisphenol A (BPA) exposure leads to peripheral insulin resistance, and hepatic and skeletal muscle oxidative stress and lipotoxicity during adulthood in the female sheep offspring. To investigate transcriptional changes underlying the metabolic outcomes, coding and non-coding (nc) RNA in liver and muscle from 21-month-old control and prenatal BPA-treated (0.5mg/kg/day from days 30 to 90 of gestation; Term: 147days) female sheep were sequenced. Prenatal BPA-treatment dysregulated:1) expression of 194 genes (138 down, 56 up) in liver and 112 genes (32 down, 80 up) in muscle; (2) 155 common gene pathways including mitochondrial-related genes in both tissues; 3) 1415 gene pathways including oxidative stress and lipid biosynthetic process specifically in the liver; (4) 192 gene pathways including RNA biosynthetic processes in muscle; (5) 77 lncRNA (49 down, 28 up), 14 microRNAs (6 down, 8 up), 127 snoRNAs (63 down, 64 up) and 55 snRNAs (15 down, 40 up) in the liver while upregulating 6 lncRNA and dysregulating 65 snoRNAs (47 down, 18 up) in muscle. Multiple ncRNA correlated with LCORL, MED17 and ZNF41 in liver but none of them in the muscle. OPLS-DA plots identified mRNAs PECAM, RDH11 and ABCA6, and miRNAs MIR200B and MIR30B in liver and mRNAs CAST, NOS1 and FASN and miRNAs MIR26B and MIR29A in muscle as gene signatures of gestational BPA exposure. These findings provide mechanistic clues into the development and/or maintenance of the oxidative stress and lipid accumulation and potential for development of mitochondrial and fibrotic defects contributing to the prenatal BPA-induced metabolic dysfunctions.

2022-07-08 | GSE190327 | GEO

Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [ncRNA-Seq]

2022-07-08 | GSE190326 | GEO

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.

2024-04-21 | GSE219111 | GEO

Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [RNA-Seq]

Project description:Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [RNA-Seq]

| PRJNA786647 | ENA

Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [ncRNA-Seq]

Project description:Developmental Programming: Impact of Prenatal Bisphenol-A Exposure On Liver and Muscle Transcriptome of Female Sheep [ncRNA-Seq]

| PRJNA786648 | ENA

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.

2020-06-18 | GSE150236 | GEO

Developmental programming: Changes in mediators of insulin sensitivity in prenatal bisphenol A-treated female sheep.

Project description:Developmental exposure to endocrine disruptor bisphenol A (BPA) is associated with metabolic defects during adulthood. In sheep, prenatal BPA treatment causes insulin resistance (IR) and adipocyte hypertrophy in the female offspring. To determine if changes in insulin sensitivity mediators (increase in inflammation, oxidative stress, and lipotoxicity and/or decrease in adiponectin) and the intracrine steroidal milieu contributes to these metabolic perturbations, metabolic tissues collected from 21-month-old female offspring born to mothers treated with 0, 0.05, 0.5, or 5 mg/kg/day of BPA were studied. Findings showed prenatal BPA in non-monotonic manner (1) increased oxidative stress; (2) induced lipotoxicity in liver and muscle; and (3) increased aromatase and estrogen receptor expression in visceral adipose tissues. These changes are generally associated with the development of peripheral and tissue level IR and may explain the IR status and adipocyte hypertrophy observed in prenatal BPA-treated female sheep.

| S-EPMC6443435 | biostudies-literature

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.

2020-12-30 | GSE158436 | GEO

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.

2021-10-31 | GSE178775 | GEO

Developmental programming: Transcriptional regulation of visceral and subcutaneous adipose by prenatal bisphenol-A in female sheep.

Project description:BackgroundBisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood.ObjectiveTo determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots.MethodsRNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested.ResultsThere were 179 differentially expressed genes (padjusted < 0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways.ConclusionPrenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.

| S-EPMC7418632 | biostudies-literature

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