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In utero exposure to environmental factors can modify the development of allergies later in life whereby the mechanisms of the feto-maternal crosstalk still remain largely unknown. Murine studies revealed that inflammatory maternal signals elicited by chronic helminth infection within the placenta imprint a distinct gene expression profile related to the Vitamin-D-receptor (VDR)-inflammation-axis. We thus investigated whether pro- or anti- inflammatory immune responses as well as VDR and related gene expression within the placenta differ between women from helminth-endemic and non-endemic areas. A prospective pilot study was conducted in Munich, Germany (helminth non-endemic) and Lambaréné, Gabon (helminth-endemic). At delivery, clinical information alongside placenta tissue samples and maternal and cord blood were obtained for further laboratory analysis. Schistosoma haematobium infection was detected in 13/54 (23%) Gabonese women. RT PCR revealed significantly lower gene expression of VDR, Cyp27b1, Foxp3 and IL10 in Gabonese compared to German placentae as well as significantly lower levels of plasma IgG4 in newborns resulting in a significantly higher IgE/IgG4 ratio. These findings demonstrate that exposure in utero to different environments alters placental gene expression and thus possibly plays a role in the development and modulation of the immune system of the offspring.

In utero exposure to environmental factors can modify the development of allergies later in life whereby the mechanisms of the feto-maternal crosstalk still remain largely unknown. Murine studies revealed that inflammatory maternal signals elicited by chronic helminth infection within the placenta imprint a distinct gene expression profile related to the Vitamin-D-receptor (VDR)-inflammation-axis. We thus investigated whether pro- or anti- inflammatory immune responses as well as VDR and related gene expression within the placenta differ between women from helminth-endemic and non-endemic areas. A prospective pilot study was conducted in Munich, Germany (helminth non-endemic) and Lambaréné, Gabon (helminth-endemic). At delivery, clinical information alongside placenta tissue samples and maternal and cord blood were obtained for further laboratory analysis. Schistosoma haematobium infection was detected in 13/54 (23%) Gabonese women. RT PCR revealed significantly lower gene expression of VDR, Cyp27b1, Foxp3 and IL10 in Gabonese compared to German placentae as well as significantly lower levels of plasma IgG4 in newborns resulting in a significantly higher IgE/IgG4 ratio. These findings demonstrate that exposure in utero to different environments alters placental gene expression and thus possibly plays a role in the development and modulation of the immune system of the offspring.

Vitamin D metabolism plays a pivotal role not only in bone metabolism but in a variety of tissues such as the placenta. This organ forms the feto-maternal interface, where Vitamin D deficiency and a dysregulation of its receptor VDR can lead to dysfunction and consequently adverse fetal and maternal outcomes. Moreover, it hasbeenshownthat the reaction tomaternal immunological triggers, such as inflammation or infection, is linked to altered expression profiles of VDR. In a murine study we showed that maternal schistosome infection indeed affects placental VDR expression and resulted in suppressed susceptibility to allergic airway inflammation in offsprings. To reproduce thesefindings inahumansetting,wemonitored in more detail the VDR expression in placenta samples. We have now started a pilot study (Placenta-Cordblood-Microbiome Study), comparing placentas from healthy German cohorts with patients from Gabon, where schistosomiasis is endemic. We analyzed gene expression levels, focusing not only on VDR expression but also other candidate genes like IL-10 or IFNy. To link VDR expression profiles to the offspring’s allergy susceptibility, we will perform detailed allergy questionnaires until up to five years after child’s birth. Our preliminary data, so far, indicates that VDR gene expression profiles are even varying between the fetal and the maternal side of the placenta, emphasizing its important role within this organ.