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Influence of the in utero environment on the risk of allergy development for the child

Final Report Summary - INUTERAL (Influence of the in utero environment on the risk of allergy development for the child)

INUTERAL:
Influence of the in utero environment on the risk of allergy development for the child

Aim
The aim of this project is to assess if differences in the in utero environment can influence the risk of allergy development for the child, and whether these in utero differences are related to lifestyle. Since, allergic symptoms usually appear early in life, and maternal allergy is a higher risk factor than paternal allergy for the risk of the child to develop allergy, it is likely that priming occurs already in utero at the foetal stage. Therefore, within this project the aim is to investigate the in utero environment in detail in relation to lifestyle and environmental influences.

The following specific questions are addressed:
1) Does the in utero environment differ, with regard to microRNA expression or protein and mRNA expression of a selection of immune relevant genes, between mothers with and without allergy, as well as between those with different lifestyles?
2) If there are in utero mRNA expression differences do they originate from epigenetic differences?
3) Is the IgE present in the placenta specific against certain allergens or naturally occurring and does it originate from the mother or the foetus?
4) Are Hofbauer cells (placental macrophages) polarised, and are this polarisation influenced by maternal allergen-sensitisation and the presence of inflammation (histological chorioamnionitis)?

Results per question
1) mRNA levels of 17 immune relevant genes have been analyzed by means of quantitative real-time PCR in 36 placentas. These 36 placentas were selected such that 18 placentas came from families with an anthroposophic lifestyle and 18 with a conventional lifestyle. Within both these groups 9 mothers were sensitised (have allergen-specific IgE in their blood) and 9 were non-sensitised. Furthermore in total 7 families were living on a farm and 11 fathers were also sensitised. mRNA levels were measured both at the maternal and foetal side of the placenta. We could show that at the maternal side, STAT4 and GATA3 expression is related to the maternal allergen sensitisation. The expression of these genes was confirmed to be present at the protein level. Expression of IL-12(p40) was related to living on a farm on the maternal side of the placenta and to paternal sensitisation on the foetal side of the placenta. Expression of CD14 was increased at the foetal side of the placenta when the families were living on a farm.
Together these data indicate that environmental factors (lifestyle and allergen sensitisation status) can influence the in utero environment on the levels of gene expression. Changes in gene expression could affect the placental cytokine production, and intrauterine environment for the foetus. This could in turn influence the development of the foetal immune system and its risk to develop (allergic) diseases later in life.
These data have been published in the following article:
M. Joerink, Oortveld M., Stenius F., Rindsjö E., Alm J., Scheynius A. (2010) Lifestyle and parental allergen sensitization are reflected in the intrauterine environment at gene expression level. Allergy 65 (10): 1282-1289

See attached document for the full summary.