Detection of Fetal Cells in the Maternal Kidney during Gestation in the Mouse

Abstract

It has been reported that fetal cells migrate into maternal blood and organs. Since these fetal chimeric cells could be involved in maternal allogeneic tolerance to the fetus, the fetal chimeric cells might be implicated in maternal-fetal immunology and development of maternal autoimmune diseases. However, the mechanism and role of fetal microchimerism remains unclear. We aimed to describe the mechanism by which fetal cells become associated with maternal organs during pregnancy, using a mouse fetal microchimerism model. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice, which are useful for tracking the behavior of fetal cells in the maternal body, were mated with transgenic males expressing enhanced green fluorescent protein (GFP), and the presence of GFP-positive cells were examined in peripheral blood and organs of pregnant mothers. By flow cytometry, we showed that 0.95 +/- 0.48% of mononuclear cells detected in the maternal peripheral blood were GFP-positive, and thus of fetal origin, during the first gestational week. This value decreased to 0.10 +/- 0.13% during the third gestational week (p < 0.05). GFP-positive cells were detected in the extraglomerular mesangial region and among the epithelial cells of the proximal renal tubule of the maternal kidney. These GFP-positive cells also expressed angiotensin II receptor subtype 2 (AT2), which is known to participate in regulating organogenesis and vasoreactivity. Fetal cells expressing AT2 may therefore be involved in the regulation of vascular tone in the maternal kidney. These observations suggest that fetal cells could influence maternal renal function through activation of the AT2 signaling.