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Inflammasome and intrauterine growth retardation



Researchers at our laboratory are showing for the first time a direct role of NLRP7, an inflammasome protein in human pregnancy. NLRP7 would thus be responsible for defects in the establishment of fetal-maternal circulation, defects often associated with intrauterine growth retardation.

Published on 21 May 2019
Intrauterine growth retardation (IUGR) is one of the main causes of pathological pregnancies that cause different disabilities in children (intellectual, motor, pulmonary...). IUGR also causes other diseases such as diabetes, obesity, hypertension that will develop later in adulthood. In the majority of cases, IUGR is related to a failure in the placenta that does not properly ensure the nutrients and gaz exchanges between mother and the fetus. Since 2010, numerous deregulations have been reported in the function of cellular inflammasome in relation to IYGR..

In 2015, we were interested in the study of the member 7 of the inflammasome family, the NLRP7 protein. Neither the expression profile nor the biological functions of NLRP7 were known in normal and in IUGR pregnancies. In collaboration with the University Hospital of Grenoble, the maternity hospital of Poissy-Saint-Germain-en-Laye and the Royal Women's Hospital of Melbourne, we demonstrated that the NLRP7 protein is directly involved in the proliferation of placental cells and that it is regulated by hypoxia, the causal parameter of placental insufficiency. We also demonstrated that NLRP7 could contribute to the defects in the establishment of feto-maternal circulation, defects often associated with IUGR. Indeed, the invalidation of the NLRP7 gene at the trophoblast level increased the early invasion of trophoblast cells into the maternal endometrium (lining of the uterus). Analysis of sera and placental tissues from cohorts of normal pregnant women and women with IUGR showed an overexpression of NLRP7 and an increase in the inflammatory response.

This work reports for the first time a direct role of the NLRP7 member of the inflammasome family in the control of human pregnancy. Further experiments are needed to understand the potential role of this protein in the development of other pregnancy disorders.
The inflammasome is an oligomeric protein complex involved in innate immunity.
NLRP7 is the inflammasome member the most commonly expressed in the placenta.
Placental hypoxia denotes the decrease in the oxygenation of the placenta.
The trophoblast is the functional unit of the placenta, responsible for the transfer of nutrients.

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Concerning intrauterine growth retardation