One of the most critical stages in establishing a pregnancy is the implantation of the embryo in the wall of the uterus. Although the accumulation of immune cells known as DCs has been observed in the uterus after fertilization and prior to implantation, their function was not known.
However, Steffen Jung and colleagues, at The Weizmann Institute of Science, Israel, have now discovered that mouse uterine DCs are crucial for implantation and that they function to ensure that new blood vessels form in the wall of the uterus; they do not function by dampening immune responses to the embryo, as had been anticipated.
The authors used mice engineered such that they could be depleted of all their DCs (including those in the uterus) by administration of a toxin. Depletion of DCs in both normal mice and mice lacking the ability to mount an immune response resulted in a severe defect in implantation, indicating that uterine DCs had a role in implantation that was independent of their effects on the immune system.
Further analysis revealed that this role was to produce two factors (sFlt1 and TGF-beta-1) critical for coordinating blood vessel formation.
The importance of this work and the implications for understanding potential causes of human infertility where implantation is impaired as well as other pregnancy related complications (for example, preeclampsia) are discussed by both the authors and, in an accompanying commentary, Jeffrey Pollard, at Albert Einstein College of Medicine, New York.
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