Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives
Chrysoula Dosiou and Linda C. Giudice*
*Division of Endocrinology and Metabolism, Department of Medicine, +Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305
* To whom correspondence should be addressed. E-mail: giudice{at}stanford.edu.
The endocrine and the immune systems interact closely duringimplantation and maintenance of pregnancy. One of the most strikingexamples of this communication is at the level of the decidua(endometrium of pregnancy). Here, under the influence of sexsteroids, there is a dramatic increase of a unique populationof lymphocytes, the uterine natural killer cells (uNK cells),in early pregnancy. These cells derive predominantly from asubset of peripheral blood NK cells, that under hormonal influencegets recruited to the uterus. In mice, uNK cells play an importantrole in the development of placental vasculature. The role ofthese cells in human pregnancy is still not definitively established;however, they are believed to promote placental and trophoblastgrowth and provide immunomodulation at the maternal-fetal interface.In contrast to their presumptive role in the maintenance ofa healthy pregnancy, uNK cells and peripheral NK cells are dysregulatedin unexplained recurrent pregnancy loss. Herein, we review NKcell populations, their changes in number and function in alteredendocrine environments during the menstrual cycle and pregnancy,the current data on their potential role in unexplained recurrentpregnancy loss, and mechanisms for potential therapies targetedto NK cell function for this enigmatic disorder.
Key words: natural killer (NK) cells •
recurrent pregnancy loss •
uterine NK cells •
hormonal regulation
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