Inflammation as a cause of placental dysfunction in high-risk pregnancies
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1
University of Manchester, Maternal and Fetal Health Research Centre, United Kingdom
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2
University of Manchester, Faculty of Life Sciences, United Kingdom
Inflammation during pregnancy is associated with stillbirth and life-long diseases in surviving newborns. The mechanism underlying this association is mostly unknown. We hypothesize that cytokines induce placental dysfunction, resulting in fetal nutrient/oxygen deprivation. To test this hypothesis we determined the inflammatory profile in human placentas from high-risk pregnancy associated with reduced fetal movements (RFM) and investigated the effects of identified cytokines on placental function.
Methods: Term placentas were collected from women experiencing RFM and compared with uncomplicated pregnancies. ELISA and immunohistochemistry were used to determine cytokine levels in placental lysates and assess their localization respectively. Placental explants from normal pregnancies were treated with interleukin (IL)-1β and the effects on inflammation, hormone production and cell turnover were determined.
Results: Levels of IL-1β and IL-1 receptor antagonist (IL-1Ra) were increased in RFM pregnancies, while levels of IL-6 and TNF-α remained unchanged. Placentas from pregnancies with RFM also showed a decreased expression of IL-10, suggesting a pro-inflammatory imbalance within the tissue. RFM placentas also had elevated numbers of CD45+ cells within placental parenchyma, which were highly positive for IL-1Ra. Treatment of placental explants with IL-1β led to decreased secretion of hormone (hCG) and immune activation.
Conclusion: This study identifies a pro-inflammatory profile in high-risk pregnancies associated with RFM, characterized by a predominant involvement of the IL-1 system and decreased anti-inflammatory IL-10. IL-1β-treated placental explants showed altered function. These results emphasize the importance of inflammation-induced placental dysfunction in human high-risk pregnancies and subsequent fetal mortality and morbidity.
Acknowledgements
The authors would like to acknowledge funding from Tommy's the baby charity and the Canadian Institute of Health Research.
Keywords:
Placenta,
prenatal inflammation,
IL-1beta,
Placental dysfunction,
IL-1 receptor antagonist,
High risk pregnancy
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Girard
S,
Heazell
AE,
Derricott
H,
Sibley
CP,
Allan
SM and
Jones
RL
(2013). Inflammation as a cause of placental dysfunction in high-risk pregnancies.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00066
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Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Sylvie Girard, University of Manchester, Maternal and Fetal Health Research Centre, Manchester, United Kingdom, sylvie.girard@recherche-ste-justine.qc.ca