Maternal Cells are Widely Distributed in Murine Fetuses in Utero1

Abstract

Passage of maternal cells into conceptuses in utero is recognized but poorly defined in species with hemochorial placentation. Despite the potential importance for such a phenomenon in vertical disease transmission, only limited data address the frequency of material to fetal cell trafficking or the developmental stage of its initiation. A murine model system, involving transfer of LacZ-, scid/scid, or wild type (+/+) blastocysts to pseudo-pregnant, LacZ+ transgenic ROSA26 females provided both flow cytometric and in situ information. In 100% of the late-gestation pregnancies studied, nucleated LacZ+ maternal cells crossed to conceptuses. In 90% of scid/scid fetuses, nucleated maternal cells were present in at least one lymphoid organ and often in more than one organ. Thymus was the most frequent site for maternal cell detection while the highest proportions of maternal cells were found in liver. Maternal cells were also visualized in fetal lung, heart, and bone marrow. Maternal cell trafficking into scid/scid fetuses commenced about midgestation, coincident with maturation of a placental circulation. In late-gestation +/+ fetuses, maternal cells were found extensively throughout bone marrow but not in other organs. The presence of maternal cells within primary lymphoid organs of fetuses may influence the repertoire of the developing fetal immune system and may be an underappreciated mechanism for vertical disease transmission.

Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and Integrins

“…To explore the mechanism of maternal stem cell transmission to conceptuses in utero, we delivered cells intravenously at E17 and assessed fetal organs collected at E21, as well as 3-12 weeks after delivery. Marleau et al [7] reported maternal cells first appearing in fetal thymus at E12.5, coincident with the maturation of the hemochorial interface [1]. Morphologically heterogeneous maternal cells were present predominantly in bone marrow and thymus in more than 90% of late-gestation fetuses.…”

“…Placenta is not an absolute barrier: cells can pass from mother to fetus and vice versa [1][2][3][4]. Maternal cells have been demonstrated in fetal circulation [5] and in liver, spleen, thymus, thyroid, and skin of neonatal organs [6].…”

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

“…Although it could be argued that these findings reflect maternal to fetus trafficking during labor, other studies indicate that transfer occurs in the course of gestation because maternal DNA has been reported in fetal blood from second and third trimester pregnancy terminations (4,5). In experimental studies, maternal cells were found in the marrow cavities of developing bones in immune-competent mice (6).…”

Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

“…(Forni et al, 1988). This may indicate that much of the force driving development of the immune system is derived from exposure to alloantigens encountered in utero (Claas et al, 1988;Piotrowski and Croy, 1996) rather than postnatal exposure to pathogens. Unfortunately, in the study of Forni et al (1988), T helper cell differentiation was not assessed, and therefore it is not known whether memory T helper cell numbers increase in absence of xenogeneic challenge.…”