Naturally acquired microchimerism

Abstract

Bi-directional transplacental trafficking occurs routinely during the course of normal pregnancy, from fetus to mother and from mother to fetus. In addition to a variety of cell-free substances, it is now well recognized that some cells are also exchanged. Microchimerism refers to a small number of cells (or DNA) harbored by one individual that originated in a genetically different individual. While microchimerism can be the result of iatrogenic interventions such as transplantation or transfusion, by far the most common source is naturally acquired microchimerism from maternal-fetal trafficking during pregnancy. Microchimerism is a subject of much current interest for a number of reasons. During pregnancy, fetal microchimerism can be sought from the mothers blood for the purpose of prenatal diagnosis. Moreover, studies of fetal microchimerism during pregnancy may offer insight into complications of pregnancy, such as preeclampsia, as well as insights into the pathogenesis of autoimmune diseases such as rheumatoid arthritis which usually ameliorates during pregnancy. Furthermore, it is now known that microchimerism persists decades later, both fetal microchimerism in women who have been pregnant and maternal microchimerism in her progeny. Investigation of the long-term consequences of fetal and maternal microchimerism is another exciting frontier of active study, with initial results pointing both to adverse and beneficial effects. This review will provide an overview of microchimerism during pregnancy and of current knowledge regarding long-term effects of naturally acquired fetal and maternal microchimerism.

Fig. 1. Microchimerism (Mc) in three generations

(A) Proband as infant (red) exchanges Mc with her mother (blue), resulting in maternal Mc in the infant and fetal Mc in the mother. (B) As an adult, proband (red), still harboring maternal Mc, experiences pregnancy herself (green) and acquires new source of fetal Mc. (C) Later, proband (red), child (green), and proband’s mother (blue), all with persistent Mc from maternal and/or fetal sources.

Fig. 2. Male cell in female liver by fluorescence in situ hybridization

Reproduced with permission from JAMA, 2004; 291:1128, Copyright © 2004 American Medical Association.

Fig. 3. Female cells in pancreas of a boy with type 1 diabetes

Immunohistochemistry for insulin was used with concomitant FISH for × and Y chromosomes. (A) Fluorescence microscopy showing a female cell among male cells. (B) Light microscopy of the same cells pictured in (A); the red-brown staining identifies β cell insulin expression. (C) Overlay of (A,B) showing identical cells by both FISH and immunohistochemistry; reproduced with permission from Proc. Natl. Acad. Sci. USA (2007) 104:1640.