VARITI-5 : Study of Variations of Serum ITIH5 in Women During the Genital Life and in Pathological Situations

The five proteins of the ITI (Inter-α-trypsin inhibitor) family, are essential components of the extracellular matrix, the dynamics of which they participate in the processes of cellular differentiation and proliferation. I. The ITIH1, ITIH2, ITIH3 and ITIH4 genes seem to be overwhelmingly expressed in the liver, this organ secreting then the corresponding proteins in the general circulation. The only data on ITIH5 indicate that this gene is poorly expressed in the liver and that the major source of its expression is the placenta. In the context of genetic studies on the syndrome of Mayer-Rokitansky-Küster-Hauser (congenital aplasia of the uterus and vagina), the investigators have shown the involvement of ITIH5 and implemented validation experiments of this gene in mice. The investigators have shown that the production of ITIH5 by the uterus varies greatly depending on the physiological state of this organ, especially during pregnancy and the estrous cycle. The investigators also found that most of the production ITIH5 was located in the uterus. Therefore, the serum dosage of ITIH5 could be used clinically as a new biological marker specific to the uterus. This non-invasive biological marker could thus assist in the diagnosis and the understanding of uterine pathologies. ITIH5 rate being correlated to endometrial proliferation, its dosage could be an early and non-invasive marker of endometriosis. The peak of production of ITIH5 by the uterus at the time of embryo implantation window indicates that the assay could provide a better assessment of endometrial receptivity to embryo. It then could be a hand tool of diagnosis in some cases of early repeated miscarriages, and secondly, a prognostic tool for embryo implantation in the context of in vitro fertilization.

The investigators conducted an initial feasibility study on the serum dosage of ITIH5, which was approved by the ethics committee of the University Hospital of Rennes. This first step has been validated. Now, the project is to perform a quantitative analysis of ITIH5 and to correlate clinical and biological data of relevant pathological and physiological situations. This project was the subject of a national and international patents of which the University Hospital of Rennes is promoter.