Impact of maternal stress on offspring immune development and later life health and disease

Primary supervisor: Dr. Rebecca Gentek

Secondary supervisor: Dr. Kahyee Hor

Additional secondary supervisor: Dr. Bert Malengier-Devlies (currently postdoctoral fellow in the Gentek lab)

Lay Abstract

Pain, distress and poor mental health during pregnancy can directly impact the mother, but also have long-lasting effects on the developing foetus. This phenomenon is known as pathological or developmental “programming”. For example, maternal stress correlates with a higher incidence of atopic disease in affected children, and an increased risk for airway infections has also been reported. However, because studies in humans can only be correlative, it remains unclear if and how maternal stress and disease susceptibility are causally linked. 

This project therefore uses experimental animal models to investigate the link between maternal stress and later life health and disease. This allows us to establish cause-consequence relationships in such complex biological systems as pregnancy and foetal development. We focus on the immune system, which is often dysregulated in disease. The immune system starts developing in the womb, and many of these earliest immune cells persist in tissues until long after birth. Similarly, all of the immune progenitor cells that can be found in the bone marrow originate from foetal stages. Immune cells and their progenitors are thus likely candidates that could mediate long-term effects of maternal stress.

 Specifically, we study airway mast cells, the key type of immune cells in atopic disease. We know that foetal mast cells can sense perturbations during pregnancy and respond to them. We hypothesise that foetal mast cells become inappropriately activated by maternal stress, and that these changes persist after birth, leading to heightened susceptibility to atopic disease and/or infection in the offspring. 

This work will improve our understanding of how maternal stress affects the developing immune system, and how this impacts later life disease. Ultimately, this project may therefore aid in identifying children at risk of developing atopic disease or airway infections