Prenatal programming: adverse cardiac programming by gestational testosterone excess
| Autor: | Arpita Vyas, Vasantha Padmanabhan, Ebony Gilbreath, Vanessa Hoang, Kristy Mietelka |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Testosterone Excess medicine.medical_specialty Heart Ventricles Prenatal Programming medicine.medical_treatment mTORC1 030204 cardiovascular system & hematology Article 03 medical and health sciences 0302 clinical medicine Insulin resistance Pregnancy Internal medicine medicine Animals Insulin Testosterone Ventricular remodeling 2. Zero hunger Sheep Multidisciplinary biology medicine.disease Brain natriuretic peptide Disease Models Animal Insulin receptor 030104 developmental biology Endocrinology Gene Expression Regulation Prenatal Exposure Delayed Effects Hypertension biology.protein Female Insulin Resistance Biomarkers Polycystic Ovary Syndrome Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30–90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells –c3 (NFATc3) and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. |
| Databáze: | OpenAIRE |
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