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Fetomaternal Trafficking in the Mouse Increases as Delivery Approaches and Is Highest in the Maternal Lung¹

Department of Pediatrics,³ Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts 02111 Department of Obstetrics and Gynecology,⁴ Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan Institute for Clinical Research and Health Policy Studies,⁵ Tufts Medical Center, Boston, Massachusetts 02111

ABSTRACT

The purpose of the study was to understand in more detail the natural history of fetomaternal cell trafficking in healthy pregnant mice. Our goal was to identify the best target organs and days during pregnancy for further mechanistic studies of the role of fetal cells in maternal disease and injury. C57BL/6J wild-type virgin females (n = 54) were mated with congenic enhanced green fluorescent protein (EGFP) transgenic males. During pregnancy and after delivery, female mice were euthanized, and eight organs and blood were analyzed for the presence of fetal GFP⁺ cells with flow cytometry and real-time quantitative PCR. Maternal lungs, liver, and spleen were also analyzed by fluorescent stereomicroscopy. Fetal GFP⁺ cells were first found at low frequency at Embryonic Day 11, increased to a maximum at Embryonic Day 19, and decreased rapidly postpartum. These fetal cell dynamics were significantly reproducible among all mice studied. In addition, there was a consistent distribution of fetal cells within maternal organs, with lung, liver, blood, and spleen having the greatest concentrations; these were highly correlated at all time points (P < 0.0001). Maternal lung contained 10- to 100-fold more fetal cells than any other organ, and using all three techniques, the number of fetal cells detected was the most consistent and reproducible in this organ. Stereomicroscopy showed that within the lung, fetal cells were widely and apparently randomly distributed. Using a murine model, our data demonstrate that fetomaternal cellular trafficking occurs in reproducible patterns, is maximal near term delivery, and has predilection for the maternal lung..

fetal cell microchimerism, flow cytometry, lung, pregnancy, trafficking

¹Supported by National Institutes of Health grant R01 HD049469-04 to D.W.B. Y.F. was supported by a grant from the Kanzawa Medical Research Foundation in Nagano, Japan.

Correspondence: ²Diana W. Bianchi, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Box 394, 800 Washington St., Boston, MA 02111. FAX: 617 636 1469; e-mail: dbianchi{at}tuftsmedicalcenter.org

This article has been cited by other articles:

				Y. Fujiki, K. L. Johnson, I. Peter, H. Tighiouart, and D. W. Bianchi Fetal Cells in the Pregnant Mouse Are Diverse and Express a Variety of Progenitor and Differentiated Cell Markers Biol Reprod, July 1, 2009; 81(1): 26 - 32. [Abstract] [Full Text] [PDF]