[Human pregnancy, a biological paradigm of tolerance and adaptation]

This review analyses the changes in immunological tolerance, and the systemic and local hemodynamic changes observed along human pregnancy. To underscore the conceptual importance of tolerance and adaptation the background is provided by the two main advocates of these ideas: Gandhi and Darwin. The cognate factors that determine immunological tolerance (IT), systemic (SA) and local adaptation (LA) are multiple; IT = desensitisation to paternal antigens, absence of HLA-A, roles of HLA-G, natural killer cells and their receptors; SA = decreased vascular resistance, plasma volume expansion, increased cardiac output and plasma renin activity; LA = prostacyclin, nitric oxide, kallikrein-kinin system, vasodilator arm of the renin angiotensin system, vascular endothelial growth factor (VEGF). A possible role of vasodilators in the crucial process of trophoblast invasion and uterine artery transformation is supported. The relevance of an adequate adaptation to pregnancy is highlighted not only by the intragestational complications derived from a defective process, such as intrauterine growth restriction, preterm birth, and preeclampsia -its foremost expression- but also by the long term cardiovascular complications of the mother and her offspring.