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Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
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Developmental programming: prenatal testosterone-induced epigenetic modulation and its effect on gene expression in
Niharika Sinha1, Sambit Roy1, Binbin Huang2
1Department of Animal Sciences, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA.
Biology of Reproduction
|January 14, 2020
Summary
Prenatal testosterone exposure in sheep alters ovarian gene expression and epigenetic marks, potentially contributing to polycystic ovary syndrome (PCOS) development later in life.
Area of Science:
- Reproductive Biology
- Developmental Programming
- Epigenetics
Background:
- Maternal health during fetal development influences offspring's long-term health.
- Prenatal androgen excess is linked to polycystic ovary syndrome (PCOS) in humans and animals.
- PCOS is a common endocrine disorder associated with infertility and metabolic dysfunction.
Purpose of the Study:
- To investigate epigenetic modifications in ovaries following prenatal testosterone (T) exposure.
- To determine the impact of prenatal T on gene expression in fetal and adult sheep ovaries.
- To establish a mechanistic link between epigenetic changes and PCOS-related gene expression.
Main Methods:
- Sheep model of PCOS phenotype.
- RNA sequencing (RNA-seq) to analyze gene expression in fetal (D90) and adult (Y2) ovaries.
- Chromatin immunoprecipitation (ChIP) to assess histone modifications (H3K27ac, H3K9ac, H3K4me3, H3K27me3, H3K9me3) on gene promoters.
Main Results:
- Prenatal T exposure altered gene expression in both fetal (65 genes) and adult (99 genes) ovaries.
- Histone marks showed no significant changes in fetal ovaries but were upregulated in adult ovaries (except H3K4me3 and H3K27me3).
- ChIP confirmed increased H3K27ac and H3K9ac on upregulated genes and increased H3K9me3 on downregulated genes in adult ovaries.
Conclusions:
- Prenatal testosterone exposure induces lasting epigenetic changes in the ovary.
- These epigenetic modifications correlate with altered gene expression, providing a mechanism for PCOS development.
- This study offers insights into developmental programming and its role in reproductive disorders like PCOS.
Keywords:
PCOSepigeneticsgene expressionhistone modificationsprenatal exposuresheep ovarytestosteroneMore Related Videos
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