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Maternal androgen e...
Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring.
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- Manti, Maria (author)
- Karolinska Institutet
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- Fornes, Romina (author)
- Karolinska Institutet
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- Pironti, Gianluigi (author)
- Karolinska Institutet
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- McCann Haworth, Sarah (author)
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Zhengbing, Zhuge (author)
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Benrick, Anna, 1979 (author)
- Högskolan i Skövde,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Institutionen för hälsa och lärande,Forskningsspecialiseringen Hälsa och Lärande,Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden,Translationell medicin TRIM, Translational Medicine
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- Carlström, Mattias (author)
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Andersson, Daniel (author)
- Karolinska Institutet
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- Stener-Victorin, Elisabet (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-08-05
- 2020
- English.
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In: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 116:3, s. 619-632
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Abstract
Subject headings
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- Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is suggested to increase the risk for cardiovascular disease. How PCOS may lead to adverse cardiac outcomes is unclear and here we hypothesized that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity in mice induce adverse metabolic and cardiac programming in female offspring that resemble the reproductive features of the syndrome.The maternal obese PCOS phenotype was induced in mice by chronic high-fat-high-sucrose consumption together with prenatal DHT exposure. The prenatally androgenized (PNA) female offspring displayed cardiac hypertrophy during adulthood, an outcome that was not accompanied by aberrant metabolic profile. The expression of key genes involved in cardiac hypertrophy was up-regulated in the PNA offspring, with limited or no impact of maternal obesity. Furthermore, the activity of NADPH oxidase, a major source of reactive oxygen species in the cardiovascular system, was down-regulated in the PNA offspring heart. We next explored for early transcriptional changes in the heart of newly born PNA offspring, which could account for the long-lasting changes observed in adulthood. Neonatal PNA hearts displayed an up-regulation of transcription factors involved in cardiac hypertrophic remodelling and of the calcium-handling gene, Slc8a2. Finally, to determine the specific role of androgens in cardiovascular function, female mice were continuously exposed to DHT from pre-puberty to adulthood, with or without the antiandrogen flutamide. Continuous exposure to DHT led to adverse left ventricular remodelling, and increased vasocontractile responses, while treatment with flutamide partly alleviated these effects.Taken together, our results indicate that intrauterine androgen exposure programmes long-lasting heart remodelling in female mouse offspring that is linked to left ventricular hypertrophy and highlight the potential risk of developing cardiac dysfunction in daughters of mothers with PCOS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Animals
- Diet
- High-Fat
- Dietary Sucrose
- Dihydrotestosterone
- Disease Models
- Animal
- Energy Metabolism
- Female
- Gene Expression Regulation
- Hypertrophy
- Left Ventricular
- etiology
- genetics
- metabolism
- physiopathology
- Maternal Exposure
- Mesenteric Arteries
- metabolism
- physiopathology
- Mice
- Inbred C57BL
- Myocardium
- metabolism
- pathology
- NADPH Oxidases
- genetics
- metabolism
- Obesity
- complications
- Polycystic Ovary Syndrome
- chemically induced
- Pregnancy
- Sex Factors
- Sexual Development
- Sodium-Calcium Exchanger
- genetics
- metabolism
- Ventricular Dysfunction
- Left
- etiology
- genetics
- metabolism
- physiopathology
- Ventricular Function
- Left
- Ventricular Remodeling
- Translationell medicin TRIM
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Manti, Maria
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Fornes, Romina
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Pironti, Gianlui ...
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McCann Haworth, ...
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Zhengbing, Zhuge
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Benrick, Anna, 1 ...
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Carlström, Matti ...
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Andersson, Danie ...
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Stener-Victorin, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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Cardiovascular r ...
- By the university
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University of Gothenburg
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University of Skövde
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Karolinska Institutet