OBJECTIVES: The prevalence of childhood allergic disease has increased dramatically in developed countries. The increasing prevalence of allergic disease with modern urbanisation and the early onset of disease in childhood indicates that allergy originates during prenatal life. Modern environmental changes are hypothesised to be causing deviations in fetal programming, in which the placenta plays a central role, increasing the susceptibility and prevalence of disease throughout life. We hypothesised that susceptibility to childhood allergy is determined by changes in placental function that programs immune function in the fetus in a sex-specific manner. In this study we aimed to identify candidate genes and pathways in human placental tissue that may contribute to the development of childhood allergy.
METHODS: Human placental tissue was obtained after delivery from women giving informed consent at the Lyell McEwin Hospital, Adelaide, and global gene expression was examined via microarray analysis. Placentae from pregnancies that gave rise to children with allergy by 4 years of age (n=45) were compared to placentae from children with no allergy (n=17), and sex-specific differences were also examined. Differentially expressed genes and pathways were identified using Ingenuity Pathway Analysis software.
RESULTS: Microarray analysis identified increased expression of cytokine growth factor kit ligand (KITL), its receptor kit, and matrix metalloproteinase 2 and 9 (MMP2, MMP9) in placenta associated with allergy compared to control. qPCR validation showed increased expression of these genes in female placentae compared to male placentae in control and allergy groups.
CONCLUSION: This study has identified genes known to be involved in inflammation that appear to be differentially regulated in male and female placentae, suggesting sex-specific roles in fetal development. The roles of each gene in placental function and fetal development are unknown, and may have sex-specific roles in the programming of fetal immune function and contribution of allergy susceptibility.