Around 2-3% of reproductive-age couples suffer recurrent pregnancy loses. Almost 18% of couples that wish to have children suffer infertility problems. Simultaneously, 2-3% of all pregnant women are diagnosed with spontaneous loses. The expression of HLA molecules, specially type G, the degree of trophoblastic apoptosis, the outsourcing of new neoantigens such as phospholipids, the balance between Th1/Th2/Th3 cytokines, the type and quantity of CD4+CD25+Foxp3+ lymphocytes, the kind and the activity of uterine NK cells (uNK) cells, the presence or absence of blocking antibodies, and other mechanisms play different roles in the achievement of the so-called "tolerant microenvironment" needed to develop a normal pregnancy. Therefore, both autoimmune and alloimmune mechanisms are important. We aim at studying which isolated, and specially associated, anomalies can be identified as risk markers to be able to evaluate possible treatments.

Cells that are chronically exposed to inflammatory signals are more prone to aging than those which are not exposed to such signals. Human vascular endothelial cell (HUVEC) primary cultures activated with TNF-alpha probably increase the expression of ICAM and VCAM, synthesize ROS, and express senescence markers. It is not known what the principal intracellular pathway is (although it is thought that STAT may play a role) and it is unknown if one or more proinflammatory cytokines are needed to activate NF-KB. We are trying to find out the role that IFN-alpha and/or IL-6 and IL-1B may have on the aging inflammatory phenomena and we aim at detecting the intracellular signal pathways (STAT). We are also working on the characterization of the genes involved in these abnormal biologic responses.

Cellular microparticles (CMP) are released depending on the activation and/or the presence of cell apoptosis. They are capable of activating both inflammatory and coagulation pathways. It seems that levels of CMP are higher in healthy pregnant women. A working hypothesis establishes that an increase of CMP levels may be found in recurrent pregnancy loses and preeclampsia. It is thought that their thrombophilic capacity may be higher in those patients with anti-phospholipid antibodies, especially among those with lupus anticoagulant. We want to determine MPC levels in non-pregnant healthy women, pregnant women without previous abnormal obstetric events, women with recurrent pregnancy loses, and women with severe preeclampsia. We are also evaluating whether there are differences related to the presence or absence of antiphospholipid antibodies. Finally, we will also characterize the exact type of CMP (endothelial, platelet-like, leuco-monocyte, and throphoblastic).

Identification at the molecular level of pathways and proteins associated with the senescence of endothelial cells linked to aging and inflamatory responses. New candidate targets for therapeutic intervention at the clinical level and as new molecular moieties for nanomedicine approaches to improve aging related pathologies caused by endothelial inflamatory based senescence.