When such causes are ruled out, the other source is thought to be caused by a maternal immune response. Most of the research in this arena has focused on identifying reactions at the maternal-fetal interface in the placenta. Adrian Erlebacher and colleagues, from Harvard School of Public Health, have now, however, identified new means by which maternal immune activation can lead to pregnancy failure. Here, the authors provide a mouse model of early pregnancy loss and present data that unexpectedly links the reproductive hormone secretion system to the immune system.
The mouse model shows that when a specific immune cell receptor called CD40 is activated early in pregnancy the resulting inflammatory response caused embryo resorption. The researchers traced the molecular mechanisms underlying this process, and found that the loss of the embryo was not due to fetal damage or activity at the fetal-maternal interface, but rather because the inflammatory response ultimately caused a decrease in progesterone, the hormone responsible for preparing the body for pregnancy and maintaining it until birth.
These data make it clear that the immune system, by interfering with the reproductive hormones, may contribute to human infertility, especially in cases of recurrent pregnancy loss. Further the finding that there is a link between the immune system and the reproductive hormone secretion may provide a new means of therapy for women who suffer such repeated and early pregnancy loss by targeting the mediators of such inflammatory responses.
An accompanying commentary, by Jane Salmon at the Hospital for Special Surgery, provides an overview of the immune response system, the reproductive hormone system, and places the data from the paper by Erlebacher and colleagues in context with that and potential clinical treatments.
Title: Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system
Author Contact:
Adrian Erlebacher
Harvard School of Public Health
Boston, Massachusetts
USA
aerlebac@hsph.hardvard.edu
Tel: 617-432-0924
Fax: 617-432-0084
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/1/39
Accompanying Commentary:
A noninflammatory pathway for pregnancy loss: innate immune activation?
Author Contact:
Jane E. Salmon
Hospital For Special Surgery
New York, New York
USA
salmonj@hss.edu
Tel: 212-606-1422
Fax: 212-717-1192
Journal of Clinical Investigation