Fetal origin of allergic asthma: insights on mechanistic cues and therapeutic targets arising from a mouse model of prenatal stress challenge – Fetal Programming of allergic diseases

Aims: Prenatal stress challenge is a pivotal environmental factor which has been proposed to increase the vulnerability of offspring to develop chronic immune diseases in later life. We analyze the effect of prenatal exposure to stress. Methods: BALB/c mice were exposed to sound stress during late gestation. Allergic asthma was induced in the offspring. We analyzed immune cells in lungs, bronchioalveolar fluid (BAL) and lung-draining lymph nodes as well as cytokine concentrations in the BAL. Further, stress-challenged pregnant females were treated with a progesterone derivative. Results: Stress challenge resulted in decreased serum levels of maternal progesterone. Prenatally stressed female adult offspring revealed an increased susceptibility toward asthma, mirrored by an increased airway response, influx of inflammatory cells and increased T helper 2 cytokines in the BAL. Further, we observed decreased frequencies of regulatory T cells (CD3+CD4+CD25+foxP3+). Progesterone supplementation abrogated the impaired intrauterine development as well as the susceptibility toward asthma. Conclusions: Our study revealed that prenatal stress severely interferes with the intrauterine development, resulting in offspring with an increased vulnerability toward asthma-like symptoms. Supplementation of progesterone during stress-challenged pregnancies abrogates gender-dependently the increased susceptibility toward asthma.

Allergic Asthma - Fetal Programming - Stress