Maternal androgen excess increases risk of cardiovascular disease in female animal offspring
A novel study, published in the scientific journal Cardiovascular Research, identifies that maternal androgen excess increases the risk of cardiovascular disease in female animal offspring. The findings could have important clinical implications for women with polycystic ovary syndrome (PCOS) and may explain why women with PCOS and their daughters have increased risk of developing cardiovascular dysfunction in adult life.
PCOS is an endocrine disorder that affects more than one in ten women of childbearing age and it is characterized by elevated levels of male hormones in the blood, menstrual disorders and a range of metabolic complications, including insulin resistance and obesity. While there is limited understanding of the PCOS development, environmental factors during fetal life, such as maternal obesity or exposure to male hormones (androgens) via the mother's blood, are thought to be important risk factors for disease onset later in life.
Using a mouse model of PCOS, the study revealed the presence of cardiac structural and functional changes in the female offspring of both normal-weight and obese pregnant mice exposed to the androgen dihydrotestosterone. Independent of the mothers’ diet components, adult female offspring exposed to maternal androgens in utero developed pathological cardiac hypertrophy, which was linked to early cardiac remodeling.
To conduct the experiment, the research team led by Elisabet Stener-Victorin, Professor at the Department of Physiology and Pharmacology at Karolinska Institutet, exposed mice during fetal life to diet-induced obesity and/or male hormone in the mother.
The PhD student Maria Manti, together with the research team, conducted an extensive cardiovascular assessment in adult female offspring to assess if these environmental factors affected the mice’s cardiac structure and function, and if so, how these factors interacted with each other.
They next assessed whether these cardiac changes were related to gene expression changes within the heart. In a subset of exposed animals, cardiac gene expression was assessed in neonatal mice (one day after delivery) and early cardiac changes were revealed which could account for the cardiac dysfunction later in life.
“Our study provides novel insight into the mechanisms that may lead to increased risk of developing cardiovascular disease in PCOS. We revealed that exposure to male hormones during the critical period of fetal life is a stronger factor than maternal obesity in PCOS, which has a long-lasting impact on the cardiovascular profile of female offspring”, says Elisabet Stener-Victorin.
The study has been funded via grants from the Swedish Research Council, Swedish Heart and Lung Foundation, Novo Nordisk Foundation, the Strategic Research Programme in Diabetes at Karolinska Institutet and the Regional agreement on medical training and clinical research between Stockholm County Council.
Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring.
Manti M, Fornes R, Pironti G, McCann Haworth S, Zhengbing Z, Benrick A, et al
Cardiovasc. Res. 2019 Aug;():