Molecular regulation of fetal growth and prenatal heart development

What is it about?

Normal intrauterine growth of the embryo and fetus is essential for immediate as well as long term health after birth. In humans, impaired prenatal growth resulting in reduced birth weight increases the risk of various chronic diseases in later life, including heart disease. Different conditions have been identified to cause intrauterine growth restriction, as for example maternal malnutrition during pregnancy or placental dysfunction. The molecular mechanisms that are affected by these conditions and ultimately inhibit overall fetal as well as organ growth are poorly understood, however. We identified the central cellular regulator of nutrient and energy metabolism, cell growth and proliferation, mTORC1 (mechanistic target of rapamycin complex 1), as being important for fetal development in mice. Pharmacological inhibition of mTORC1 during pregnancy reduces body weight and heart size in the offspring at birth and has long term consequences for cardiac morphology, tissue composition and function in adulthood.

Featured Image

Why is it important?

The identification of molecular mechanisms regulating fetal body and organ growth is a key step to better understand how adverse environmental or maternal conditions during pregnancy impact on the offspring´s health and disease. Apart from functional impairment or structural defects of certain organs observed immediately after birth, this furthermore includes a phenomenon known as fetal or developmental programming. The latter is defined as a disturbance of intrauterine growth which permanently alters cellular processes after birth, thereby increasing the susceptibility for chronic diseases in adulthood. By characterizing mTORC1 as an important regulator of intrauterine growth, our study implies that any condition inhibiting mTORC1 in the fetus (including nutrient and energy restriction, reduced oxygen supply or side effects of certain drugs) would negatively influence the offspring´s health at birth or later in life.