Blocking CRH (left) results in fewer pregnancies unless T cells are absent (bottom).


Embryos are at least half foreign to their mothers. Now, George Chrousos (National Institutes of Health, Bethesda, MD) and colleagues have found that the cells that help an embryo implant also kill off some of the mother's T cells—the ones that might otherwise reject the embryo as foreign.

The pathway begins with corticotropin-releasing hormone (CRH). As a stress hormone in the body, CRH is first proinflammatory (via mast cell degranulation) and then antiinflammatory (via effects in the brain that induce cortisol production). A similar sequence of events may take place during pregnancy. An inflammatory process is needed to initiate implantation of the embryo into the wall of the uterus. But then CRH, as detailed by Chrousos, induces the expression of the death protein FasL. This results locally in the death of Fas-expressing activated T lymphocytes.Blockade of this process with a CRH antagonist results in a 50–70% reduction in the number of successful implantations in pregnant rats. This reduction occurs thanks to T cells. In nude rats, which lack T cells, the number of implantation sites returns to normal. ▪


Makrigiannakis, A., et al.
Nat. Immunol.