Sex specific differences in placental gene expression in pregnancies complicated by asthma

Abstract

Introduction: Previous research examining the effect of maternal asthma during pregnancy on placental function and fetal outcome indicated there were sex specific differences in how the fetus responds to maternal asthma. The female fetus had reduced growth and adrenal function due to alterations in placental glucocorticoid metabolism in response to maternal asthma. Placental function, HPA activity and growth of the male fetus appeared to be unaffected by asthma or inhaled steroid use. However in the presence of a second stressor in the asthmatic maternal system which was an acute, severe asthma exacerbation, males had reduced growth and an increased incidence of stillbirth while the female fetus appeared unaffected. These data suggested male and female fetuses initiate different mechanisms to the same stress and raised the question of whether there were global differences in placental gene expression in relation to fetal sex, maternal asthma and inhaled glucocorticoid treatment. Methods: Using microarray we determined the gene expression profiles of placentae collected from male or female fetuses of normal, human pregnancies and pregnancies complicated by asthma in the presence and absence of inhaled glucocorticoid intake. Data was analysed using a Binary Tree Structured Vector Quantization algorithm which generates a gene expression map. Sites on the map where there were obvious differences in gene expression were selected for analysis. Results: Placentae from female fetuses of asthmatic mothers that did not use inhaled steroids during pregnancy had 37 gene alterations relative to the control population. Placentae from male fetuses of asthmatic mothers that did not use inhaled steroids during pregnancy had 6 gene changes relative to the control population. Placentae from female fetuses of asthmatic mothers who did use inhaled steroids during pregnancy had 22 gene alterations relative to the control population and placentae of male fetuses had no gene changes. There were 10 placental genes altered in the presence of maternal asthma that were common to both male and female fetuses. Conclusions: This preliminary data indicates that there are significant differences in how a placenta from a male fetus and female fetus respond to a maternal disease and raises the question of whether we are significantly compromising our interpretation of human placental data when we do not take the sex of the fetus into account.