Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only

Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n= 409families),womenwererecruitedbetweenthe 4thand 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airwaydiseaseinchildrenbetween3and5yearsof age,multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergicrhinitis) indaughters (adjusted OR 0.92; 95 % confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95 % CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal