Maternal microchimeric cell trafficking and its biological consequences depend on the onset of inflammation at the feto-maternal interface

Abstract

Microchimerism is defined as the presence of a small population of genetically distinct cells within a host that is derived from another individual. Throughout pregnancy, maternal and fetal cells are known to traffic across the feto-maternal interface and result in maternal and fetal microchimerism, respectively. However, the routes of cell transfer, the molecular signaling as well as the timing in which trafficking takes place are still not completely understood. Recently, the presence of inflammation at the feto-maternal interface has been linked with maternal microchimeric cells modulating organ development in the fetus. Here, we review the current literature and suggest that inflammatory processes at the feto-maternal interface tissues are a physiological prerequisite for the establishment of microchimerism. We further propose a spatio-temporal corridor of microchimeric cell migration to potentially explain some biological effects of microchimerism. Additionally, we elaborate on the possible consequences of a shift in this spatio-temporal corridor, potentially responsible for the development of pathologies in the neonate.

Keywords: Inflammation; Labor; Microchimerism; Pregnancy; Spatio-temporal corridor.

Fig. 1

The spatio-temporal corridor of maternal microchimerism a Throughout gestation, a physiological balance of pro-inflammatory (dotted line) and anti-inflammatory (dashed line) responses at the feto-maternal interface secures tolerance of the fetus. Maternal cells traffic to the fetus throughout gestation. However, at the end of pregnancy, inflammatory processes increase, causing increased attraction of cells to the feto-maternal interface and the initiation of labor and parturition. This inflammatory process causes a boost in maternal cell trafficking at term, i.e., within the physiological (green) corridor for mMC. b The shift in balance to a pro-inflammatory environment can be moved towards an earlier gestational week, e.g., due to an infection. Increased inflammation at the feto-maternal interface results in elevated maternal cell trafficking now outside the physiological corridor (red). c Temporal changes in trafficking grants MC cells access to still developing and maturating embryonic and fetal tissues, which may impact these processes. The mMC influx can take place during a critical (black) or less sensitive phase (white) of development or maturation, thereby dictating the risk of developing a pathology in specific organs

Fig. 2

Proposed routes for maternal cells to traffic from mother to fetus during pregnancy. a Upper panel: Maternal immune cells migrate from the intervillous space (IVS) across the syncytiotrophoblast and cytotrophoblast cells of a terminal villus and intravasate a fetal capillary (FC) situated in the villous stroma (VS) to enter the fetal circulation. Lower panel: Maternal cells located in the decidua (DC) basalis bypass the cytotrophoblast layer of an anchoring villus and migrate towards a fetal capillary (FC) to get access to the fetal circulation. b Free floating maternal cells in the AF are swallowed and inhaled by the fetus. Upon intake, the maternal cells subsequently need to transmigrate epithelial layers of the relevant tissues to gain access to the fetal circulation (not shown). c Maternal immune cells traffic from the decidua parietalis to the chorionic membrane and transmigrate the endothelial layer of a fetal vessel gaining access to the fetal blood. Some other maternal cells cross the chorionic and amniotic membranes to enter the amniotic fluid (AF). d Maternal cells that managed to intravasate extra-embryonic capillaries in the placental villi (Fig. 2a) and chorionic membrane (Fig. 2b) get access to the fetal circulation via the umbilical cord