Maternal background strain influences fetal–maternal trafficking more than maternal immune competence in mice

Abstract

The objective of this study was to determine if fetal-maternal cell trafficking is affected by maternal immune competence and/or parental background strain using fluorescence-activated cell sorting (FACS). In our experience the sensitivity of FACS allows for the detection of 5 fetal in 107 maternal cells and assessment of cell surface phenotype. Wild-type C57BL/6J (n=18), FVB/NJ (n=15), and immunodeficient B6129S7-Rag1tm1Mom/J (n=16) female mice were mated to C57BL/6J males homozygous for the green fluorescent protein (GFP) transgene. Single cell suspensions of maternal lung, liver, spleen, bone marrow, and blood were analyzed between late gestation (day e16–18) and one day post-partum for the number of GFP-positive fetal cells in relation to 107 maternal cells and the percentage of GFP-positive cells that expressed the surface markers CD11b, CD29, CD34, CD44, or CD105. The highest relative proportions of GFP-positive fetal cells were observed in maternal lungs and livers from immunocompetent allogenic females. Among congenic matings, fetal cell microchimerism was higher in immunodeficient compared with immunocompetent females. Maternal strain and strain differences between the mother and father statistically significantly affected both the numbers of fetal cells and the relative distribution of cell types in maternal organs. The highest relative proportion of fetal cells was observed in allogenic matings with immunocompetent females. Since allogenic matings are more similar to those that occur in humans, future studies using animal models of microchimerism should consider incorporating this type of experimental design.

Comprehensive Analysis of Genes Expressed by Rare Microchimeric Fetal Cells in the Maternal Mouse Lung1

“…We have previously suggested that fetal cells in the maternal organs may be MSCs [35]. Earlier work from our laboratory showed expression of surface markers on fetal cells that were characteristic of MSCs [8,15]. Another group demonstrated the presence of fetal MSCs in the bones PRITCHARD ET AL.…”

“…In humans, trophoblast deportation is hypothesized to be important for induction of immune tolerance to the fetus [32] and is elevated in pre-eclampsia [32,33]. Further evidence comes from previous work in our laboratory showing that allogeneic matings have more fetal cell trafficking [15], suggesting that fetal cell transfer during pregnancy is affected by genetic differences between the mother and fetus. It is possible that fetal cell microchimerism plays a role in the development of maternal immune tolerance.…”

“…The work of other groups has suggested that microchimeric fetal cells consist of multiple, more differentiated cell types, such as lymphocytes [3,7,8], hepatocytes [9,10], neurons [11], cardiomyocytes [12,13], endothelial cells [7], and thymocytes [14]. Our group has further demonstrated that fetal cells, especially within a single organ, such as the maternal lung, comprise a phenotypically diverse population, as exemplified by expression of surface markers typically found on both immature and mature cell types of multiple lineages [8,15]. Currently it is unknown whether (1) committed cells enter the maternal circulation and transdifferentiate, (2) a variety of committed cells cross the placenta en masse, (3) multipotent stem progenitor cells differentiate to multiple cell types, or (4) a variety of unipotent stem progenitor cells differentiate along their commitment lineages [16].…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…At 36 th week of gestation, 100% of pregnant women have fetal cells in their circulation and after delivery and 30-50% of healthy women have detectable fetal cells in their blood from 4 weeks to decades after delivery [279,282] (Table 12). Interestingly, in mice maternal background strain and strain differences between the mother and father significantly affected fetalmaternal trafficking (both the number of fetal cells and the relative distribution of cell types in maternal organs) more than maternal immune competence [284].…”

Pregnancy‐Acquired Fetal Progenitors as Natural Cell Therapy

“…Mouse studies have suggested that histocompatibility is a key player associated with higher levels of microchimerism [Bonney and Matzinger, 1997;, although recent studies have implied that maternal background strain may be more important [Fujiki et al, 2008b;Kallenbach et al, 2011]. Mouse studies have suggested that histocompatibility is a key player associated with higher levels of microchimerism [Bonney and Matzinger, 1997;, although recent studies have implied that maternal background strain may be more important [Fujiki et al, 2008b;Kallenbach et al, 2011].…”