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Prenatal programming: adverse cardiac programming by gestational testosterone excess.

Arpita K Vyas1, Vanessa Hoang1, Vasantha Padmanabhan2

  • 1Department of Pediatrics and Human Development, Michigan State University, E. Lansing, MI, 48824, USA.

Scientific Reports
|June 23, 2016
PubMed
Summary

Prenatal exposure to excess testosterone in female sheep disrupts cardiac insulin signaling, leading to adverse left ventricular remodeling and increased risk of cardiovascular disease later in life.

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Area of Science:

  • Reproductive Endocrinology
  • Cardiovascular Physiology
  • Developmental Programming

Background:

  • Adverse prenatal events can program future cardiovascular disease.
  • Prenatal testosterone excess in sheep causes reproductive and metabolic issues like PCOS and hypertension in females.

Purpose of the Study:

  • To investigate if prenatal testosterone excess disrupts cardiac insulin signaling.
  • To determine if this disruption leads to adverse cardiac programming in the left ventricle.

Main Methods:

  • Examined left ventricular tissues from adult female sheep exposed to testosterone or oil during gestation.
  • Analyzed gene expression of insulin signaling and cardiac hypertrophy markers.
  • Assessed protein phosphorylation and performed histological analysis.

Main Results:

  • Prenatal testosterone excess elevated gene expression of insulin signaling (IRS-1, PI3K, mTORC1) and cardiac stress markers (NFATc3, BNP).
  • Increased phosphorylation of PI3K, AKT, and mTOR was observed.
  • Histology revealed myocardial disarray and increased cardiomyocyte diameter.

Conclusions:

  • Prenatal testosterone excess adversely affects cardiac insulin signaling pathways.
  • This leads to detrimental left ventricular remodeling and cardiac programming in female offspring.