Reproduction Abstracts (2014) 1 P285 | DOI: 10.1530/repabs.1.P285

Distinct sex-specific gene expression changes in the human placenta in association with childhood allergy at 2 years

Astrud Tuck, Annette Osei-Kumah, Zarqa Saif & Vicki L Clifton

University of Adelaide, Elizabeth Vale, South Australia, Australia.

The prevalence of childhood allergic disease has increased dramatically in developed countries. Modern environmental changes are hypothesised to be causing deviations in fetal programming, in which the placenta plays a central role, increasing the prevalence of disease. We hypothesised that susceptibility to childhood allergy is determined by changes in placental function that programs fetal immune function. In this study we aimed to identify candidate genes and pathways in human placental tissue that may contribute to the development of childhood allergy. Human placental tissue was obtained after delivery 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). Differentially expressed genes and pathways associated with allergy were identified using Ingenuity Pathway Analysis software and validated by qPCR. Microarray analysis identified placental gene changes in dermatological and respiratory disease networks in males, and immunological disease and immune cell trafficking networks of female offspring who developed an allergy. qPCR validation showed altered expression of interleukin 13 receptor alpha 1 (IL13RA1), ORM (yeast)-like protein isoforms 3 (ORMDL3) and matrix metalloproteinase 9 (MMP9) (P<0.05). These immune genes were also expressed in a sex-specific manner. This study has identified immune genes that are differentially regulated in male and female placentae. The roles of each gene in placental function and fetal development are unknown, and may have sex-specific functions in the programming of fetal immune function and allergy susceptibility.

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