If a Woman Is Pregnant and Has Intercourse With Different Man Can the Baby Absorb His Traits
Cell Adh Migr. 2007 Jan-Mar; ane(i): xix–27.
Cell Migration from Infant to Female parent
Gavin S Dawe
oneDepartment of Pharmacology; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
Xiao Wei Tan
2Institute of Molecular and Prison cell Biology; Singapore
Zhi-Cheng Xiao
twoConstitute of Molecular and Cell Biology; Singapore
3Section of Clinical Research; Singapore General Hospital; Singapore
4Section of Anatomy; Yong Loo Lin School of Medicine; National Academy of Singapore; Singapore
Received 2007 Feb 27; Accepted 2007 Feb 28.
Abstract
Fetal cells migrate into the mother during pregnancy. Fetomaternal transfer probably occurs in all pregnancies and in humans the fetal cells tin persist for decades. Microchimeric fetal cells are found in various maternal tissues and organs including claret, os marrow, skin and liver. In mice, fetal cells have besides been constitute in the brain. The fetal cells also announced to target sites of injury. Fetomaternal microchimerism may have important implications for the immune condition of women, influencing autoimmunity and tolerance to transplants. Further understanding of the ability of fetal cells to cross both the placental and blood-brain barriers, to migrate into diverse tissues, and to differentiate into multiple cell types may as well advance strategies for intravenous transplantation of stem cells for cytotherapeutic repair. Here we discuss hypotheses for how fetal cells cross the placental and claret-brain barriers and the persistence and distribution of fetal cells in the mother.
Central Words: fetomaternal microchimerism, stem cells, progenitor cells, placental barrier, claret-brain barrier, adhesion, migration
Microchimerism is the presence of a small population of genetically distinct and separately derived cells within an private. This normally occurs following transfusion or transplantation.1 – 3 Microchimerism tin likewise occur between mother and fetus. Pocket-size numbers of cells traffic across the placenta during pregnancy. This commutation occurs both from the fetus to the female parent (fetomaternal)iv – 7 and from the mother to the fetus.8 – 10 Like exchange may also occur between monochorionic twins in utero.11 – 13 There is increasing show that fetomaternal microchimerism persists lifelong in many changeable women.7 , 14 The significance of fetomaternal microchimerism remains unclear. It could exist that fetomaternal microchimerism is an epiphenomenon of pregnancy. Alternatively, it could be a mechanism by which the fetus ensures maternal fitness in order to enhance its ain chances of survival. In either case, the occurrence of pregnancy-acquired microchimerism in women may accept implications for graft survival and autoimmunity. More detailed agreement of the biology of microchimeric fetal cells may too advance progress towards cytotherapeutic repair via intravenous transplantation of stalk or progenitor cells.
Trophoblasts were the first zygote-derived jail cell type found to cantankerous into the female parent. In 1893, Schmorl reported the appearance of trophoblasts in the maternal pulmonary vasculature.fifteen Afterwards, trophoblasts were also observed in the maternal circulation.16 – 20 Subsequently diverse other fetal cell types derived from fetal blood were too found in the maternal circulation.21 , 22 These fetal prison cell types included lymphocytes,23 erythroblasts or nucleated cherry blood cells,24 , 25 haematopoietic progenitorsvii , 26 , 27 and putative mesenchymal progenitors.14 , 28 While information technology has been suggested that minor numbers of fetal cells traffic across the placenta in every human pregnancy,29 – 31 trophoblast release does non appear to occur in all pregnancies.32 Likewise, in mice, fetal cells have also been reported in maternal claret.33 , 34 In the mouse, fetomaternal transfer also appears to occur during all pregnancies.35
Anatomy of the Placenta
Human and rodent placentation is hemochorial, the fetomaternal interaction between the two blood circulations involving directly physical interaction between maternal claret and the chorionic trophoblasts.36 The fetal and maternal claret circulates in channels lined by these zygote-derived cells within the placental region known every bit the labyrinth in mice or the fetal placenta in humans (Fig. 1). In the homo, the channels through which the fetal claret flows, the chorionic villi, form trees with numerous branches and sub-branches terminating in villous blunt-endings. The maternal claret flows in the relatively open up intervillous space. In contrast in the mouse, the maternal blood flows through a labyrinthine network of interconnected cavities or lacunae.36 A layer of trophoblast cells forms the interface betwixt the maternal blood and the fetal tissues. It is these trophoblast cells that form the placental barrier between maternal and fetal circulation. In the human, this interface consists of a syncytium of syncytiotrophoblasts direct contacting the maternal claret (Fig. 2B). In the first trimester, there is also a layer of replicating mononuclear cytotrophoblasts beneath the syncytiotrophoblasts. In contrast, in mice there are three layers of trophoblasts. The outer layer consists of mononuclear cytotrophoblasts while the centre and inner layers are syncytiotrophoblastic.36 Between the trophoblasts and the fetal blood there are a trophoblastic basement membrane, in some but not all interfaces a core of extracellular matrix and/or pericytes, an endothelial basement membrane, and fetal capillary endothelial cells36 (Fig. 2B). Fetal blood enters and leaves the fetal placenta/labyrinth via the umbilical cord, whereas maternal blood enters and leaves the fetal placenta/labyrinth via the utero-placental circulation.
A simplified diagrammatic representation of the structure of the human being placenta (adapted from Georgiades et al.36) and hypothesized mechanisms of fetomaternal jail cell traffic. From the cease of the starting time trimester, maternal blood flows into the fetal placenta via the maternal spiral arteries, through the intervillous space bathing the branches of the villous trees and out through the maternal veins (red arrows on left-hand side). The fetal blood enters via the umbilical cord and circulates to the fetal capillaries in the villous trees. A layer of zygote-derived trophoblasts, in humans a syncytium of syncytiotrophoblasts, on the surface of the villous trees (dark light-green) forms the barrier betwixt the fetal tissues and the maternal blood. Zygote-derived trophoblasts also progressively invade the placental bed and line the maternal vasculature. By the third trimester the maternal spiral arteries are lined through to the (im), while the maternal veins are lined to the edge between the decidua basalis (db) and basal plate (bp). In the mouse, the analogue of the fetal placenta is labyrinthine and the trophoblastic invasion of the maternal blood vessels does non extend beyond the junctional zone analogous to the basal plate. Hypothesized mechanisms of fetomaternal prison cell traffic include (i) displacement of trophoblasts lining the maternal vessels and intervillous space; (2) microtraumatic hemorrhage; and (3) cell adhesion and transmigration beyond the placental bulwark.
Simplified diagrammatic representations of claret-brain and placental barriers and hypothesized molecular mechanisms of cell adhesion and transmigration. (A) A simplified diagrammatic representation of multistep lymphocyte recognition and capture from claret at the blood brain bulwark (adjusted from Engelhardt48). Cells expressing α4β1 are captured by VCAM-1 expressed by endothelial cells. At that place is a rapid activation phase (seconds) that may involve lymphoid chemokines CCL19/ELC and CCL21/SLC. In that location is a prolonged adhesion stage (hours) followed by slow transmigration (hours) dependent upon binding of LFA-i to ICAM-ane and/or ICAM-2 on the endothelial cells. It is hypothesized that a like molecular machinery may explain fetal jail cell migration across the blood-brain barrier and the placental barrier. (B) A simplified diagrammatic representation of the homo placental barrier showing a hypothetical mechanism of fetal jail cell capture, adhesion and transmigration. The placental bulwark comprises of fetal capillary endothelial cells (fcec), an endothelial basement membrane (ebm), the villous cadre (vc) which at some interfaces contains pericytes (p) and extracellular matrix, a trophoblastic basement membrane (tbm), in the kickoff trimester a layer of proliferative cytotrophoblasts (ct), and a multinucleated syncytium of syncytiotrophoblasts (ss). In the mouse, the trophoblastic layers differ in that there are two syncytiotrophoblastic layers and the cytotrophoblastic layer is outermost facing the intervillous interface. Information technology is hypothesized that fetal cells may adhere and transmigrate across the placental barrier in a similar fashion to that by which lymphocytes cross the blood-brain barrier.
The zone adjoining the maternal surface of the fetal placenta/labyrinth is known every bit the basal plate in humans and the junctional zone or spongiotrophoblast zone in mice. This region is not perfused past fetal blood but is crossed by maternal claret channels lined by zygote-derived trophoblast cells through which the maternal claret flows in and out of the fetal placenta/labyrinth.36 This zone in plough is bordered by the maternal uterine tissue on the maternal side. The maternal uterine tissue becomes progressively invaded by zygote-derived trophoblast cells. In particular, these cells line the maternal blood vessels in the maternal uterine tissue. The maternal uterine tissues of this region, known every bit the placental bed in humans, tin can be divided into the decidua basalis adjacent to the basal plate/junctional zone and the myometrium on the maternal side. In humans, trophoblast invasion extends to the inner third of the myometrium only in mice, trophoblast invasion is shallow and is limited to the decidua basalis.36 , 37 Fifty-fifty within the decidua basalis, maternal arteries and veins remain lined past maternal endothelium rather than trophoblasts in the mouse.38 , 39 While in the human the trophoblasts stimulate arterial remodeling in the mouse uterine natural killer cells are more of import.39 – 41
The cells of the placenta itself comprise both zygote-derived and maternal cells. In mice, the zygote-derived cells include trophoblasts derived from the polar trophectoderm of the outer cell mass; fetal blood vessels and mesenchyme derived from the allantoic mesenchyme, which in turn is derived from the primitive ectoderm of the inner prison cell mass; and fetal blood cells of mesodermal lineage. Meanwhile, the maternal cells of the mouse placenta include uterine cells and cells coming from the maternal blood.36 It is by and large assumed that the origin of human placental cells is similar to those in the mouse, although not lineage studies accept been performed on human placentae.36 Still, in that location is debate over whether the homo allantoic vasculature, through which the fetal blood passes, is of trophectodermal or epiblast/hypoblast origin.36 , 42
The similarities in the anatomy of placentation and placental claret catamenia in mice and humans36 , 39 and the role of analogous genes in mouse and homo placentation43 make mouse placentation a proficient model for many aspects of human placentation. However, at that place are important anatomical differences,36 , 39 in item the difference between the villous nature of the human fetal placenta and the labyrinthine nature of the analogous mouse labyrinth and the greater role of invasion by zygote-derived trophoblasts in the maternal circulation in the human placenta.
Cell Traffic Across the Placenta
The machinery by which cells are exchanged across the placental bulwark is unclear. Possible explanations include deportation of trophoblasts, microtraumatic rupture of the placental blood channels or that specific cell types are capable of adhesion to the trophoblasts of the walls of the fetal blood channels and migration through the placental barrier created by the trophoblasts (Fig. 1i–1iii). Intervillous thrombi containing mixed maternal and fetal cells occur in the fetal placenta/labyrinth.44 , 45 Histological defects in the continuity of the trophoblasts lining the vasculature of the placenta are also reported.46 , 47 Together these observations advise the possibility that fetomaternal hemorrhage within the fetal placenta/labyrinth may allow exchange of cells between the fetal and maternal circulation. Microtraumatic dislodgment of trophoblasts from the trophoblast-lined claret channels through which the maternal blood passes may besides explain why trophoblasts appear in maternal apportionment. The microtraumatic hypothesis of cell exchange does non appear consistent with the hypothesis that fetomaternal microchimerism may be of adaptive value to the fetus but fits well with the hypothesis that fetomaternal microchimerism is an epiphenomenon of pregnancy with potential pathological consequences.
An alternative hypothesis is that cells cross the placental barrier by mechanisms alike to the active adhesion and transmigration that occurs across high endothelial venule (HEV) endothelium in peripheral lymph nodes and at the claret-brain bulwark (BBB).48 Intriguingly, in the mouse at least some of the fetal cells that enter the mother are also capable of crossing the blood encephalon barrier into the brain.35 , 49
At the BBB and HEV, lymphocyte migration across the endothelial membrane involves a multistep process of recognition and recruitment from the blood involving tethering/rolling or capture, activation, adhesion and finally transmigration (Fig. 2A). In both HEV endothelium and BBB, the last stage of transmigration involves binding of LFA-1 expressed past the lymphocytes to ICAM-one in HEV endothelium and to ICAM-1 and/or ICAM-ii at the BBB.48 , fifty , 51 In the HEV endothelium, the ICAM-1 besides appears to exist involved in the adhesion preceding transmigration, whereas at the claret encephalon barrier VCAM-1 is involved in lymphocyte capture and adhesion. Fetal cells crossing the placental barrier must transmigrate both the fetal capillary endothelial jail cell layer and the trophoblast cell layers (Fig. 2B).
The fetal capillary endothelial jail cell layer expresses a number of jail cell adhesion molecules including PECAM-ane and ICAM-1.52 , 53 While, there is VCAM-1 expression in umbilical cord endothelium there appears to be no testify for VCAM-1 expression on fetal capillary endothelium in normal placenta at term.52 , 53 As PECAM-i plays a role in integrin-mediated neutrophil adhesion and endothelial transmigration,54 – 56 including migration of CD34+ positive cells57 such equally the fetal cells in maternal blood,7 we hypothesize that information technology is besides a candidate for contribution to fetal prison cell transmigration across the fetal capillary endothelium (Fig. 2B). The functional ligand for PECAM-i in transmigration is unknown, but information technology is possible that it is an αvβ3 integrin.58 It is possible that multiple fetal jail cell types cross the placental barrier by different mechanisms.
Once the fetal cells take crossed the fetal capillary endothelium, they must adjacent cantankerous the trophoblast layer. Trophoblasts express ICAM-1 in vitro and in vivo59 – 61 and monocytes bind to ICAM-one expressed past trophoblasts in an LFA-ane-dependent manner.60 Similarly, the migration of Toxoplasma gondii beyond epithelial barriers, including the placental barrier comprised of trophoblast cells, involves interaction of the parasite adhesion molecule, MIC2, with the intercellular adhesion molecule ane (ICAM-1).62 Together these studies suggest that the molecular appliance for maternofetal transmigration may be present at the placental barrier. Although in that location is show for greater in vivo expression of ICAM-1 on the upmost surface of the villous syncytiotrophoblasts exposed to the maternal claret,60 ICAM-1 is also nowadays throughout the stroma of the chorionic villi,60 , 61 although it has not been clearly established that information technology is expressed on the basal surface of the trophoblasts facing the villous core. Trophoblasts also express VCAM-1.63 – 65 Thus the molecular apparatus for fetomaternal transmigration of fetal cells expressing LFA-1 may too be nowadays at the trophoblast jail cell layer. Once the fetal cells accept crossed the fetal capillary endothelial cell layer, we hypothesize that they cross the trophoblast cell layer once again in a manner like to that in which lymphocytes cross the BBB (Fig. 2B).
We promise that this speculative hypothesis regarding the mechanisms of fetomaternal cell traffic may stimulate further research and that future studies will decide whether active fetomaternal adhesion and transmigration occurs and elucidate the molecular mechanisms involved.
Timing of Onset of Fetomaternal Traffic
In mice, fetal cells generally outset announced in the mother in the 2d week of pregnancy35 (see also Fig. 3). Numbers of fetal cells are nowadays in maternal blood past GD10 to GD12 days (gestational days, the day of vaginal plug detection being designated GD0) in pregnancies from syngenic and allogenic crosses; however the cells do not appear in blood in until GD13 to GD16 in pregnancies from outbred crosses.66 The appearance of fetal cells in maternal blood at GD10 to GD12 in syngenic and allogenic crosses is consistent with the institution of uteroplacental circulation. Maternal blood first appears in the labyrinth betwixt GD9 and GD10 and extensive fetal capillary formation occurs past GD12.39 , 67 This coincides with the onset of fetal apportionment on the completion of organogenesis at GD9 to GD10.36 In humans, fetal DNA has been detected in maternal blood equally early as four weeks and five days after conception and both fetal cells and Dna are consistently detected from seven weeks.68 , 69 Thus in humans, the get-go appearance of fetal cells in maternal blood occurs slightly earlier the completion of fetal organogenesis, the onset of fetal circulation to the placenta, and the advent of maternal blood inside the fetal placenta. Plugs of invading trophoblast cells, which block the tips of the uteroplacental spiral arteries, are progressively confused after 10–12 weeks70 and blood just becomes evident in the intervillous space of the fetal placenta afterwards ten weeks gestation.71 Effective arterial circulation of the placenta is not established until effectually the twelfth week of gestation39 , 72 , 73 when the human embryo has largely completed the organogenesis stage.36 In the mouse, the timing of the appearance of fetal cells in maternal blood is consistent with the hypothesis that fetomaternal substitution occurs betwixt fetal and maternal claret at the placental barrier in the fetal placenta/labyrinth. In the fetal placenta/labyrinth, the maternal blood comes into straight contact with the zygote-derived trophoblast and information technology has been proposed these may besides be deported into the maternal apportionment.66 The fetal placenta/labyrinth is also very rich in fetal hematopoietic stalk cells74 – 76 and it has been suggested that these cells might able to drift into the maternal blood.66 The earlier appearance of fetal cells in maternal blood in humans may propose more than agile migration of sure fetal cells. Potentially there may be multiple jail cell types and phases of migration involved. More detailed investigation of the time course of the appearance of maternal blood in the placenta and the advent of fetal cells in maternal blood in humans may be informative.
Time form of fetal jail cell engraftment and persistence in the mouse encephalon. Adult female mice received intraventricular injection of the excitotoxic NMDA to produce a diffuse brain lesion or were untreated. The mice were crossed with adult male enhanced greenish fluorescent protein (EGFP) transgenic Green Mice. Fetomaternal microchimerism in the brain was assayed at various fourth dimension points: gestational days (GD) seven and 14, the day of parturition (P0), and at seven days (P7), iv weeks (P4W) and eight weeks (P8W) post partum (north = 3–8 per grouping at each time point). The number of fetal cells relative to total cells present in a brain cake centered about the site of the injection was quantified by existent-time PCR for the EGFP factor in genomic DNA. Procedures were every bit previously described.49 There are peachy individual differences, however, in those mothers in which fetal cells were detected in the brain, the number of fetal cells detected in the brain increases by iv weeks post partum and declines again by 8 weeks post partum. Overall, in those mothers in which fetal cells persist at 4 weeks and eight weeks post partum, at that place are greater numbers of fetal cells in the lesioned brains.
The reason for the delay in the appearance of fetal cells in maternal blood in outbred mouse crosses is at present unknown. Outbred crosses were also observed to result in delayed and reduced trophoblast invasion of the decidua basalis.66 It may be that the appearance of fetal cells in maternal blood on outbred crosses is due to a more ambitious allowed response; alternatively the delay may be due to a delay in the maturation of the placenta and maternal apportionment to the labyrinth. It is hoped that further studies may elucidate the issue.
Intriguingly in syngenic pregnancies, fetal cells were detected in mouse lungs and to a bottom extent spleen and kidney in the first week of gestation before they robustly appear in detectable numbers in maternal circulation.35 , 66 One explanation might be that, consistent with the appearance of trophoblasts in maternal lungs in humans,15 these cells are trophoblasts. Thus one might hypothesis that the primeval phase of fetomaternal microchimerism involves deportation of zygote-derived trophoblasts equally they invade the decidua basalis to line the maternal claret vasculature. In particular, the fate of the trophoblasts that plug the ends of the maternal arteries of the uteroplacental circulation may exist to become dislodged into maternal circulation equally maternal blood period begins to intermission through into the fetal placenta/labyrinth. Trophoblasts being large are quickly cleared from maternal claret as they go lodged in the microvasculature of the lung and to a lesser extent other organs. While the studies discussed here have fabricated important contributions to establishing the time course of fetomaternal traffic, the question of whether dissimilar zygote-derived cell types prove unlike time courses of traffic has not been investigated in depth. It is hoped that future studies will address this of import issue.
Frequency and Persistence of Fetomaternal Microchimerism
Fetomaternal microchimerism appears to occur with slap-up frequency following human pregnancy. It has been suggested that fetomaternal traffic occurs in all pregancies.14 Moreover fetal cells are reported to persist in the mother for decades. Male cells have been found in maternal blood fifty-fifty decades after pregnancy,7 , 77 including in one case in which the women was last pregnant with a male child 27 years earlier.7 Fetal cells likewise may persist for even longer subsequently engrafting maternal bone marrow14 and perchance other organs. By engrafting into niches such every bit the bone marrow, fetal cells may as well be able to proliferate and reinfiltrate blood or other tissues later. There is strong evidence that fetal cells with the characteristics of mesenchymal cells practise engraft the os marrow. Male Dna was detected in 48% of CD34-enriched apheresis products from nonpregnant female marrow donors.1 Male cells were also detected in all os marrow samples from women who had previously been pregnant with males, including one adult female who was final pregnant with a son 51 years earlier.fourteen
The absence of Y chromosome markers in samples from women who had never born sons in some studiesxiv strongly supports the argument that the male cells observed originate from the fetus. Still, it is important to note that there are crucial caveats in the use of the Y chromosome alone as a mark for fetomaternal microchimerism that may accept led to over interpretation of the incidence and persistence of fetomaternal microchimerism in humans. Male cells have been found in the claret of women without sons.78 , 79 Male cells may occur in the blood of as many equally viii–10% of healthy women without sons and no known history of ballgame.79 It has been speculated that the male person cells ascend from unrecognized spontaneous abortions, vanished male twins, an older blood brother transferred by the maternal apportionment, or sexual intercourse. However, a history of unrecognized spontaneous abortions or sexual intercourse cannot explain all cases of the presence of male cells in females as another written report detected the presence of the Y chromosome in normal liver from 7 of eleven female fetuses and 5 of half dozen female children.80 Such microchimerism may be best explained, past fetofetal transfer from an undetected vanishing male twin or maternofetal transfer of male cells harbored past the mother. Estimates of the frequency of vanishing twins range from 3.seven–100% of pregnancies81 however not all twins share connected placenta vasculature, specially at the early stages of development at which many twins disappear. Maternofetal transfer to the mother may also accept occurred if the mother'due south mother had a history of blood transfusion, transplantation or previous pregnancy with a male fetus. Information technology is difficult to estimate how often male person cells in females could arise as a result of fetofetal or maternofetal transfer. Although ane might await such events to exist rare, the incidence may be loftier enough to have biased estimates of the incidence of fetomaternal microchimerism in humans. While the possibility that the Y chromosome could also enter the mother via microchimerism as a consequence of previous claret transfusion or transplantation has been considered in most studies, the possibility that male cells detected in the female parent may have arrived via fetofetal or maternofetal transfer to the mother in utero has not exist systematically excluded. Conclusive proof of fetomaternal microchimerism in humans would crave the use of other paternal markers that differentiate betwixt the male parent of the fetus and the father of the mother. One scenario might exist to investigate cases where the mother and the female parent'due south male parent share a genetic mutation or polymorphism not carried by the father of the fetus. In such cases, evidence of genetic markers derived from the father of the fetus in the mother could provide more than conclusive evidence of fetomaternal microchimerism in humans. If the genetic mutation or polymorphism caused disease the presence of fetal cells in the diseased tissue could too offer evidence of the potential of fetomaternal tissue repair.
In contrast, to the proposition that fetal cells are retained for decades subsequently nearly every man pregnancy,vii , xiv the memory of fetal cells in mice appears more sporadic and rarely persists for more a few weeks post partum. The use of mice bearing unique genetic markers such equally, the cytogenetic marker chromosome, T626 , 33 and more recently transgenic mice bearing genetic markers such equally enhanced dark-green fluorescent protein (EGPF)35 , 49 , 66 has conclusively demonstrated fetomaternal microchimerism. The number of mice in which fetal cells can be detected in maternal blood and the number of fetal cells in maternal claret declines towards the end of gestation, at least in syngenic and allogenic crosses.66 Beyond the first week postpartum, fetal cells are rarely detected in maternal blood;35 , 66 although they take been found in some mice at 21 days postal service partum following allogenic crosses and at 42 days post partum, simply not 21 days post partum, following outbred crosses.66 Also, in maternal bone marrow, spleen, liver, heart, lung and kidney fetal cells practise non appear to be retained by maternal mice beyond the start week post partum.35 Even inside the first week post partum, the retention of fetal cells is sporadic and highly variable between individuals.35 Our own observations suggest that there might be greater retention of fetal cells within the brain as although fetal prison cell numbers are low, cells persist to 4 weeks post partum49 (see also Fig. iii). Nonetheless, by 6–viii weeks mail partum, the number of fetal cells has fallen below the limits of detection in claret and all organs studied, including uninjured brain66 (encounter also Fig. 3). Although the numbers of fetal cells present were very low, fetal cells did persist at eight weeks mail partum in some of the lesioned maternal brains (Fig. 3). Together, these data advise the possibility that, although fetal cells are cleared from the blood and some organs within a few weeks postpartum in mothers of syngenic and allogenic crosses, some fetal cells may remain harbored longer-term in certain niches. In contrast, fetal cells take been detected in the blood of some mice at 42 days post partum following outbred crosses.66 Additionally, at that place is limited evidence that in some, just not all mice, repeated pregnancies may lead to greater retention of fetal cells,35 , 49 which may suggest that in some mothers in that location is longer-term retention of fetal cells. Nonetheless, the elapsing of fetal prison cell retention in those few mice in which fetal cells practice persist has non been systematically investigated. The reasons for the large individual differences in the numbers of fetal cells retained and the duration of retentiveness are not known.
During pregnancy the female parent develops allowed tolerance to the fetus but subsequently pregnancy this suppression of the maternal allowed response to the fetus is lifted.82 It is conceivable that, although fetomaternal cell traffic probably occurs in every pregnancy, persistence of microchimeric fetal cells after pregnancy depends upon the immunocompatibility between the mother and fetus. This might explain why fetomaternal microchimerism does not persist in all mothers. The greater preservation of fetal cells in the encephalon than the blood would be consequent with an immune rejection hypothesis, the brain being an immune privileged site.83 Nevertheless, it is difficult to reconcile the hypothesis that immune rejection explains the great inter-individual variability and low charge per unit of fetal cell persistence in syngenically crossed mice66 as there is less allowed rejection on transplantation between syngenic mice. Although some differences between the mother and fetus may be an reward as it has been noted that, despite reducing placental expression of major histocompatibility complex (MHC) genes, major histocompatibility complex expression is often reestablished in the most invasive trophoblast cells and may contribute to an immunoprotective issue on the fetus.84
In conclusion, although it has non been studied systematically and there are obvious methodological differences between the mouse and human studies, in that location appears to greater likelihood of long-term retention of microchimeric fetal cells in humans than in mice. This deviation in the retention of fetal cells may be consequent with the hypothesis that fetomaternal microchimerism has developed as a mechanism by which the fetus ensures maternal fitness. Equally mice wean their offspring past 3–4 weeks postpartum, there would exist no need for the fetal cells to keep to survive. In contrast, human mothers nurse their offspring for many months and thereafter continue to nurture their offspring for many decades then at that place may be an adaptive advantage to fetal jail cell persistence. Alternatively, if fetal cells have adverse effects on the mother, it may be that rodents take developed greater maternal resistance to fetal prison cell infiltration as they have far more offspring over a far shorter life span.
Intriguingly, at that place may in fact be greater retention of fetal cells in outbred mice than in syngenic or allogenic crosses.66 That humans, who are generally outbred, retain fetal cells may exist further evidence against the immunocompatibility hypothesis for fetomaternal microchimeric persistence. It is hoped that future studies may investigate the determinants of fetal cell retentiveness. The immunological hypothesis would predict that immunosuppression from late pregnancy and through the post-partum catamenia would increase fetomaternal microchimerism. Another hypothesis might be that hormonal changes coinciding with the later stages of pregnancy and the post partum period atomic number 82 to rejection of fetal cells. This hypothesis would predict greater fetomaternal microchimerism in mother who did not consummate the normal hormonal sequela of commitment and peri- and post-partum hormonal changes. In humans, there is indeed testify that spontaneous and induced abortions increase the frequency and level of male microchimerism,79 , 85 but this may equally be explained by trauma associated with abortion leading to greater fetomaternal exchange.
Distribution of Microchimeric Fetal CellS
The microchimeric fetal cells in the mother appear to be of multilineage potential. Y chromosome bearing cells have been identified in numerous tissues, including skin, liver, kidney and bone marrow, in good for you women and in women with autoimmune diseases86 – 92 and other none allowed diseases such as hepatitis C93 and cervical cancer.94 There is now a large literature on fetomaternal microchimerism, peculiarly in autoimmune illness, and overall there appears to be evidence of increased fetal cell presence in diseased tissues than healthy tissues.27 , 95 It is debatable whether microchimerism plays a role in triggering autoimmune illness,86 – 89 , 91 perchance by stimulating graft-host disease or host-graft disease,96 or whether fetal cells home in on diseased tissue and contribute to tissue repair.27 , 96 In systematic lupus erythematosus, for example, information technology appears that microchimeric fetal cells are more likely to be plant in severe cases than in mild cases97 suggesting that the fetal cells are not causing the disease but rather are targeting the diseased maternal tissue once the harm reaches a threshold level.27 Similarly, in an animate being model of excitotoxic brain injury we found greater numbers of fetal cells in the injured brain region.49 Fetal cells may also persist longer at sites of injury than in uninjured tissue (Fig. 3). This suggests the possibility that fetal cells may target to specific tissues and contribute to tissue repair or function.
There are various manners in which fetal cells might come to target damaged tissue. Sometimes the mechanism past which the zygote-derived cells are sequestered in particular tissues may be mechanical as has been hypothesized for the entrapment of big trophoblast cells in the capillaries of the microvasculature of the lung.fifteen Likewise, targeting of injured tissues may just be a mechanical process whereby tissue damage is associated with micro-harm to the blood vessels and cells of all types are more likely to leak out into the damaged tissue. Another hypothesis is that fetal cells invade all maternal tissues but merely discover a niche conducive to survival in damaged tissues. Alternatively, if this is a process that has evolved to allow the fetus to care for the mother to raise fetal survival, the fetal cells may actively invade the damaged tissue by a physiological mechanism of adhesion and transmigration across the claret vessel walls followed by active migration through the tissue to sites of damage.
Recently, Khosrotehrani and colleagues98 have used in vivo bioluminescence imaging of fetal cells in which the paternal mark was VEGF receptor 2 promoter controlled luciferase cistron expression to demonstrate that fetal cells contribute to neoangiogenesis. This in vivo bioimaging arroyo volition be extremely valuable in determining the extent to which fetal cells invade damaged tissues. Tracking genetically modified fetal cells or the behaviour of fetal cells in genetically modified mothers information technology may exist possible to address important questions about the mechanisms past which fetal cells engraft maternal tissues and home in on injured tissue.
Types of Fetal Cells Involved in Fetomaternal Microchimerism
The fetal cell type or types responsible for fetomaternal microchimerism are unknown. Candidates include all cell types in fetal claret and trophoblasts. However, considerable evidence points towards the conclusion that fetal stem or progenitor cells may too be involved. Subsequent pregnancies appear to trigger further proliferation and mobilization to maternal blood of fetal cells acquired during previous pregnancies.34 The very fact that fetal cells tin can be detected decades later on pregnancy7 , 14 , 99 is strong evidence that these cells are replicating in the mother. Moreover, women with older sons accept a greater number of male cells suggesting proliferation over time.93 Although fetal cells were not detected in all ex-breeder mice those mice that had fetal cells in the brain tended to have higher numbers than in mice that had just delivered one litter suggesting accumulation or proliferation of fetal cells.49 The numbers of fetal cells detected in the maternal brain also showed marked postnatal increment between the last twenty-four hours of gestation and four weeks post partum (Fig. three). This evidence that fetal cells can proliferate in the mother is fairly persuasive, but the alternative possibility that the fetal cells engraft in one niche and so later on remobilize to some other niche without increasing in number has not been excluded.
Fetal cells announced indistinguishable from maternal tissues years after pregnancy and can bear epithelial, leukocyte, hematopoietic, hepatocytic, renal or cardiomyocytic markers.27 , 95 , 100 That microchimeric fetal cells also appear to be able to differentiate to adopt cellular characteristics of various host organs suggests that they may be stem or progenitor cells. In injured mouse brain, we have found fetal cells expressing various morphologies, localization and immunocytochemically stained protein markers characteristic of various encephalon cell types including perivascular macrophages, neurons, astrocytes and oligodendrocytes.49 While the prove for differentiation may announced persuasive, important alternative hypotheses take nevertheless to exist excluded. Notably there have yet to be clear-cut examples of functional differentiation of microchimeric fetal cells. For example, it would be important to bear witness that apparent neuronal differentiation does not merely involve location, morphology and expression of a few poly peptide markers but instead that this differentiation leads to functional neuronal characteristics such as the capacity to fire activeness potentials and synaptic connectivity to repair damaged circuitry. Likewise in the example of apparent oligodendrocytic differentiation, morphology and protein expression should be accompanied by functional wrapping of axons, and recovery of motor role in demyelination models.
At present there is little evidence for or against fusion as a mechanism of the apparent differentiation in microchimeric fetal cells. While a binucleated fetal cell was observed juxtaposed to a blood vessel in the brain in a niche in which other fetal cells adopted a perivascular macrophage-like graphic symbol,49 it is unclear whether this represents a fusion effect, a cell sectionalization outcome, or a multinucleated prison cell blazon. Systematic and careful study of fusion events in fetomaternal microchimerism will exist important in interpreting whether apparent differentiation of fetal cells is in fact the result of cell fusion. Typically cell fusion in iatrogenic microchimerism following transplantation has been studied by fluorescent in situ hybridization (FISH) for X and Y chromosome markers. The presence of multiple Ten chromosomes in the cells bearing Y chromosomes has been taken as evidence of fusion. However, the written report of cell fusion by this method in fetomaternal microchimerism is complicated. Not only may the Y chromonsome not be a specific marker for fetal cells every bit discussed above, just the trophoblasts, one of the jail cell types which contribute to fetomaternal microchimerism, can be multinucleated and due to the mosaic nature of the placenta could naturally comport multiple X chromosomes together with the Y chromosome in cases of vanishing female person twins or in the rodent model where near litters contain both male and female offspring. Other strategies will exist required to investigate fusion in fetomaternal microchimerism. For example, combining labeling for paternal-specific and maternal specific markers (e.g., crossing male person EGFP transgenic mice with DsRed transgenic mice). Alternatively, Cre/lox recombination might be used to notice cell fusion events101 but this approach would crave in utero implantation of homozygous embryos, which may change fetomaternal prison cell traffic.
If the multilineage differentiation capacity of microchimeric fetal cells does prove to be genuine and functional this suggests that the fetal cells responsible are stalk cells. The type of stem prison cell or stalk cells involved is controversial. There is some show implicating haematopoietic stalk cells. For instance, male person cells that persist in maternal blood after pregnancy are CD34+/CD38+,7 carry like proliferative haematopoeitc progenitor cells in vitro culture,102 and in haematopoietic tissues, such as the lymph nodes and spleen, the majority of microchimeric male cells express CD45.95 In dissimilarity, there is also show suggesting that fetal mesenchymal stem cells (fMSC) are involved. Fetal MSCs have been identified in maternal blood during pregnancy.28 , 103 Fisk and colleagues appear to favor the interpretation that these cells are fetal mesenchymal stem cells because, at least when found in the bone marrow, male cells in mothers were immunophenotypically mesenchymal.14 However, information technology has been pointed out that the extent of the multilineage differentiation of microchimeric male cells argues against a strictly mesenchymal lineage.104 Indeed, unless i accepts the notwithstanding controversial concept of stem prison cell plasticity and transdifferentiation, neither haematopoietic nor mesenchymal stalk cells could explicate the full range of differentiation, for instance into neural prison cell types,49 that has been reported. The diversity of cell types into which microchimeric fetal cells tin patently differentiate suggests that, if a single stem or progenitor cell type is involved, it is a very early stalk jail cell type.27 , 95 , 100 Bianchi and colleagues accept referred to these cells as pregnancy-associated progenitor cells (PAPC) and appear to favor the interpretation that they may be a relatively early stem cell type retaining multilineage potential.27 , 91 , 95 , 100 The culling possibility that numerous cell types of dissimilar lineage enter the female parent has not been excluded. Perchance the involvement of a number of cell types including various types of early stalk cells could better explain the multifariousness of differentiation reported.
Conclusions and Future Prospects
Fetal cells exhibit a remarkable power to migrate across the placenta into the mother and to integrate with diverse maternal tissues and organs, evidently homing in particularly to sites of harm and disease.49 , 97 Much remains to be learned virtually the basic biology of fetomaternal microchimerism. The jail cell blazon or types involved have all the same to be conclusively characterized. If various cell types are involved, it will be important to understand the fourth dimension course of the migration of the diverse cell types and their persistence in the mother. Studies of the process of cellular adhesion and migration that let the cells to cross the placental barriers, infiltrate tissues and organs, cross the BBB and migrate to sites of damage will be especially informative. Although long-term persistence of fetal cells may exist less frequent in the mouse, the mouse appears to offering a useful model for investigating aspects of fetomaternal traffic during pregnancy.
In the longer-term, elucidation of the biology of fetomaternal microchimerism may have important implications for understanding autoimmunity and graft-host interactions. Moreover, cognition of the jail cell types and molecular mechanisms that allow for the remarkable migratory and multilineage differentiation capacity of microchimeric fetal cells in the mother may better strategies for cytotherapeutic repair. Harnessing the capabilities of microchimeric fetal cells may enhance the prospects for minimally invasive intravenous delivery of stem cells.
Footnotes
References
1. Adams KM, Nelson JL. Microchimerism: An investigative frontier in autoimmunity and transplantation. JAMA. 2004;291:1127–1131. [PubMed] [Google Scholar]
2. Reed Westward, Lee Th, Norris PJ, Utter GH, Busch MP. Transfusion-associated microchimerism: A new complexity of claret transfusions in severely injured patients. Semin Hematol. 2007;44:24–31. [PubMed] [Google Scholar]
3. Starzl TE. Chimerism and tolerance in transplantation. Proc Natl Acad Sci United states. 2004;101(Suppl 2):14607–14614. [PMC free article] [PubMed] [Google Scholar]
4. Iverson GM, Bianchi DW, Cann HM, Herzenberg LA. Detection and isolation of fetal cells from maternal claret using the flourescence-activated jail cell sorter (FACS) Prenat Diagn. 1981;i:61–73. [PubMed] [Google Scholar]
five. Herzenberg LA, Bianchi DW, Schroder J, Cann HM, Iverson GM. Fetal cells in the claret of pregnant women: Detection and enrichment by fluorescence-activated jail cell sorting. Proc Natl Acad Sci United states of america. 1979;76:1453–1455. [PMC free article] [PubMed] [Google Scholar]
half dozen. Bianchi DW, Shuber AP, DeMaria MA, Fougner Air conditioning, Klinger KW. Fetal cells in maternal blood: Decision of purity and yield by quantitative polymerase concatenation reaction. Am J Obstet Gynecol. 1994;171:922–926. [PubMed] [Google Scholar]
7. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male person fetal progenitor cells persist in maternal claret for as long as 27 years postpartum. Proc Natl Acad Sci USA. 1996;93:705–708. [PMC costless article] [PubMed] [Google Scholar]
8. Maloney S, Smith A, Furst DE, Myerson D, Rupert Thou, Evans PC, Nelson JL. Microchimerism of maternal origin persists into adult life. J Clin Invest. 1999;104:41–47. [PMC free article] [PubMed] [Google Scholar]
9. Srivatsa B, Srivatsa S, Johnson KL, Bianchi DW. Maternal cell microchimerism in newborn tissues. J Pediatr. 2003;142:31–35. [PubMed] [Google Scholar]
10. Nelson JL, Gillespie KM, Lambert NC, Stevens AM, Loubiere LS, Rutledge JC, Leisenring WM, Erickson TD, Yan Z, Mullarkey ME, Boespflug ND, Bingley PJ, Gale EA. Maternal microchimerism in peripheral blood in type i diabetes and pancreatic islet beta cell microchimerism. Proc Natl Acad Sci United states of america. 2007;104:1637–1642. [PMC free article] [PubMed] [Google Scholar]
11. van Dijk BA, Boomsma DI, de Man AJ. Blood grouping chimerism in man multiple births is not rare. Am J Med Genet. 1996;61:264–268. [PubMed] [Google Scholar]
12. Shalev SA, Shalev East, Pras E, Shneor Y, Gazit E, Yaron Y, Loewenthal R. Evidence for claret chimerism in dizygotic spontaneous twin pregnancy discordant for Downwards syndrome. Prenat Diagn. 2006;26:782–784. [PubMed] [Google Scholar]
13. Walker SP, Meagher Due south, White SM. Confined claret chimerism in monochorionic dizygous (MCDZ) twins. Prenat Diagn. 2007 [PubMed] [Google Scholar]
14. O'Donoghue One thousand, Chan J, de la FJ, Kennea North, Sandison A, Anderson JR, Roberts IA, Fisk NM. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stalk-cell trafficking in pregnancy. Lancet. 2004;364:179–182. [PubMed] [Google Scholar]
xv. Lapaire O, Holzgreve Due west, Oosterwijk JC, Brinkhaus R, Bianchi DW. Georg schmorl on trophoblasts in the maternal circulation. Placenta. 2007;28:i–5. [PubMed] [Google Scholar]
16. Douglas GW, Thomas Fifty, Carr M, Cullen NM, Morris R. Trophoblasts in circualting claret during pregnancy. Am J Obstet Gynecol. 1959;78:960–973. [PubMed] [Google Scholar]
17. Mueller UW, Hawes CS, Wright AE, Petropoulos A, DeBoni E, Firgaira FA, Morley AA, Turner DR, Jones WR. Isolation of fetal trophoblast cells from peripheral blood of significant women. Lancet. 1990;336:197–200. [PubMed] [Google Scholar]
eighteen. Chua S, Wilkins T, Sargent I, Redman C. Trophoblast deportation in pre-eclamptic pregnancy. Br J Obstet Gynaecol. 1991;98:973–979. [PubMed] [Google Scholar]
nineteen. Hawes CS, Suskin HA, Petropoulos A, Latham SE, Mueller UW. A morphologic study of trophoblast isolated from peripheral blood of pregnant women. Am J Obstet Gynecol. 1994;170:1297–1300. [PubMed] [Google Scholar]
20. Hawes CS, Suskin HA, Kalionis B, Mueller UW, Casey G, Hall J, Rudzki Z. Detection of paternally inherited mutations for beta-thalassemia in trophoblast isolated from peripheral maternal blood. Ann North Y Acad Sci. 1994;731:181–185. [PubMed] [Google Scholar]
21. Alston RL. Sit-in of foetal cells in maternal blood. J Med Lab Technol. 1969;26:224–226. [PubMed] [Google Scholar]
22. Amo H, Kajino G. Demonstration of foetal cells by chromosome assay of maternal blood. Nagoya J Med Sci. 1973;36:11–16. [PubMed] [Google Scholar]
23. Walknowska J, Conte FA, Grumbach MM. Applied and theoretical implications of fetal-maternal lymphocyte transfer. Lancet. 1969;one:1119–1122. [PubMed] [Google Scholar]
24. Bianchi DW, Flint AF, Pizzimenti MF, Knoll JH, Latt SA. Isolation of fetal Deoxyribonucleic acid from nucleated erythrocytes in maternal blood. Proc Natl Acad Sci U.s.. 1990;87:3279–3283. [PMC complimentary article] [PubMed] [Google Scholar]
25. Ganshirt D, Garritsen H, Miny P, Holzgreve W. Fetal cells in maternal apportionment throughout gestation. Lancet. 1994;343:1038–1039. [PubMed] [Google Scholar]
26. Gaillard MC, Ouvre East, Liegeois A, Lewin D. The concentration of fetal cells in maternal haematopoietic organs during pregnancy: An experimental report in mice. J Gynecol Obstet Biol Reprod (Paris) 1978;7:1043–1050. [PubMed] [Google Scholar]
27. Khosrotehrani M, Bianchi DW. Multi-lineage potential of fetal cells in maternal tissue: A legacy in opposite. J Cell Sci. 2005;118:1559–1563. [PubMed] [Google Scholar]
28. O'Donoghue G, Choolani M, Chan J, de la FJ, Kumar South, Campagnoli C, Bennett PR, Roberts IA, Fisk NM. Identification of fetal mesenchymal stem cells in maternal blood: Implications for non-invasive prenatal diagnosis. Mol Hum Reprod. 2003;ix:497–502. [PubMed] [Google Scholar]
29. Ariga H, Ohto H, Busch MP, Imamura S, Watson R, Reed Due west, Lee Th. Kinetics of fetal cellular and cell-free Deoxyribonucleic acid in the maternal circulation during and afterwards pregnancy: Implications for non-invasive prenatal diagnosis. Transfusion. 2001;41:1524–1530. [PubMed] [Google Scholar]
30. Krabchi Chiliad, Gros-Louis F, Yan J, Bronsard 1000, Masse J, Wood JC, Drouin R. Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques. Clin Genet. 2001;60:145–150. [PubMed] [Google Scholar]
31. Jackson L. Fetal cells and Deoxyribonucleic acid in maternal blood. Prenat Diagn. 2003;23:837–846. [PubMed] [Google Scholar]
32. Sargent IL, Johansen G, Chua S, Redman CW. Clinical experience: Isolating trophoblasts from maternal blood. Ann N Y Acad Sci. 1994;731:154–161. [PubMed] [Google Scholar]
33. Liegeois A, Escourrou J, Ouvre E, Charreire J. Microchimerism: A stable state of low-ratio proliferation of allogeneic bone marrow. Transplant Proc. 1977;9:273–276. [PubMed] [Google Scholar]
34. Liegeois A, Gaillard MC, Ouvre E, Lewin D. Microchimerism in pregnant mice. Transplant Proc. 1981;13:1250–1252. [PubMed] [Google Scholar]
35. Khosrotehrani K, Johnson KL, Guegan S, Stroh H, Bianchi DW. Natural history of fetal cell microchimerism during and following murine pregnancy. J Reprod Immunol. 2005;66:1–12. [PubMed] [Google Scholar]
36. Georgiades P, Ferguson-Smith AC, Burton GJ. Comparative developmental anatomy of the murine and human being definitive placentae. Placenta. 2002;23:3–xix. [PubMed] [Google Scholar]
37. Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol. 1967;93:569–579. [PubMed] [Google Scholar]
38. Adamson SL, Lu Y, Whiteley KJ, Holmyard D, Hemberger Thou, Pfarrer C, Cantankerous JC. Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev Biol. 2002;250:358–373. [PubMed] [Google Scholar]
39. Carter AM. Animate being models of human placentation - A review. Placenta. 2006 [PubMed] [Google Scholar]
40. Monk JM, Leonard S, McBey BA, Croy BA. Induction of murine spiral artery modification by recombinant human being interferon-gamma. Placenta. 2005;26:835–838. [PubMed] [Google Scholar]
41. Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nat Rev Immunol. 2006;6:584–594. [PubMed] [Google Scholar]
42. Bianchi DW, Wilkins-Haug LE, Enders Air-conditioning, Hay ED. Origin of extraembryonic mesoderm in experimental animals: Relevance to chorionic mosaicism in humans. Am J Med Genet. 1993;46:542–550. [PubMed] [Google Scholar]
43. Rossant J, Cross JC. Placental development: Lessons from mouse mutants. Nat Rev Genet. 2001;2:538–548. [PubMed] [Google Scholar]
44. Devi B, Jennison RF, Langley FA. Significance of placental pathology in transplacental bleeding. J Clin Pathol. 1968;21:322–331. [PMC costless commodity] [PubMed] [Google Scholar]
45. Batcup G, Tovey LA, Longster G. Fetomaternal blood group incompatibility studies in placental intervillous thrombosis. Placenta. 1983;4:449–453. (Spec No) [PubMed] [Google Scholar]
47. Jauniaux Due east, Hustin J. Histological examination of first trimester spontaneous abortions: The impact of materno-embryonic interface features. Histopathology. 1992;21:409–414. [PubMed] [Google Scholar]
48. Engelhardt B. Molecular mechanisms involved in T cell migration beyond the claret-brain bulwark. J Neural Transm. 2006;113:477–485. [PubMed] [Google Scholar]
49. Tan XW, Liao H, Sunday Fifty, Okabe M, Xiao ZC, Dawe GS. Fetal microchimerism in the maternal mouse brain: A novel population of fetal progenitor or stalk cells able to cantankerous the blood-brain barrier? Stem Cells. 2005;23:1443–1452. [PubMed] [Google Scholar]
fifty. Greenwood J, Etienne-Manneville S, Adamson P, Couraud PO. Lymphocyte migration into the central nervous system: Implication of ICAM-1 signalling at the blood-encephalon bulwark. Vascul Pharmacol. 2002;38:315–322. [PubMed] [Google Scholar]
51. Lyck R, Reiss Y, Gerwin Due north, Greenwood J, Adamson P, Engelhardt B. T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: The cytoplasmic tail of endothelial ICAM-one is necessary for transendothelial migration of T cells. Blood. 2003;102:3675–3683. [PubMed] [Google Scholar]
52. Lyall F, Young A, Boswell F, Kingdom JC, Greer IA. Placental expression of vascular endothelial growth cistron in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not back up placental hypoxia at delivery. Placenta. 1997;18:269–276. [PubMed] [Google Scholar]
53. Dye JF, Jablenska R, Donnelly JL, Lawrence L, Leach L, Clark P, Firth JA. Phenotype of the endothelium in the human term placenta. Placenta. 2001;22:32–43. [PubMed] [Google Scholar]
54. Muller WA, Weigl SA, Deng X, Phillips DM. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993;178:449–460. [PMC free article] [PubMed] [Google Scholar]
56. Jackson DE. The unfolding tale of PECAM-1. FEBS Lett. 2003;540:7–fourteen. [PubMed] [Google Scholar]
57. Yong KL, Watts K, Shaun TN, Sullivan A, Ings South, Linch DC. Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31) Blood. 1998;91:1196–1205. [PubMed] [Google Scholar]
58. Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA. CD31/PECAM-i is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Jail cell Biol. 1995;130:451–460. [PMC free commodity] [PubMed] [Google Scholar]
59. Labarrere CA, Faulk WP. Intercellular adhesion molecule-1 (ICAM-i) and HLA-DR antigens are expressed on endovascular cytotrophoblasts in abnormal pregnancies. Am J Reprod Immunol. 1995;33:47–53. [PubMed] [Google Scholar]
60. Xiao J, Garcia-Lloret M, Winkler-Lowen B, Miller R, Simpson K, Guilbert LJ. ICAM-1-mediated adhesion of peripheral blood monocytes to the maternal surface of placental syncytiotrophoblasts: Implications for placental villitis. Am J Pathol. 1997;150:1845–1860. [PMC free article] [PubMed] [Google Scholar]
61. Labarrere CA, Ortiz MA, Sosa MJ, Campana GL, Wernicke M, Baldridge LA, Terry C, DiCarlo HL. Syncytiotrophoblast intercellular adhesion molecule-1 expression in placental villitis of unknown cause. Am J Obstet Gynecol. 2005;193:483–488. [PubMed] [Google Scholar]
62. Barragan A, Brossier F, Sibley LD. Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2. Cell Microbiol. 2005;vii:561–568. [PubMed] [Google Scholar]
63. Rajashekhar G, Loganath A, Roy Ac, Wong YC. Expression and secretion of the vascular cell adhesion molecule-1 in human placenta and its decrease in fetal growth restriction. J Soc Gynecol Investig. 2003;x:352–360. [PubMed] [Google Scholar]
64. Cartwright JE, Balarajah G. Trophoblast interactions with endothelial cells are increased past interleukin-1beta and tumour necrosis factor blastoff and involve vascular cell adhesion molecule-ane and alpha4beta1. Exp Cell Res. 2005;304:328–336. [PubMed] [Google Scholar]
65. Rajashekhar M, Loganath A, Roy Ac, Chong SS, Wong YC. Hypoxia up-regulated angiogenin and downwardly-regulated vascular cell adhesion molecule-1 expression and secretion in human placental trophoblasts. J Soc Gynecol Investig. 2005;12:310–319. [PubMed] [Google Scholar]
66. Vernochet C, Caucheteux SM, Kanellopoulos-Langevin C. Bi-directional cell trafficking between mother and fetus in mouse placenta. Placenta. 2006 [PubMed] [Google Scholar]
67. Muntener K, Hsu YC. Development of trophoblast and placenta of the mouse: A reinvestigation with regard to the in vitro civilization of mouse trophoblast and placenta. Acta Anat (Basel) 1977;98:241–252. [PubMed] [Google Scholar]
68. Thomas MR, Tutschek B, Frost A, Rodeck CH, Yazdani North, Craft I, Williamson R. The fourth dimension of advent and disappearance of fetal DNA from the maternal circulation. Prenat Diagn. 1995;15:641–646. [PubMed] [Google Scholar]
69. Pertl B, Bianchi DW. First trimester prenatal diagnosis: Fetal cells in the maternal circulation. Semin Perinatol. 1999;23:393–402. [PubMed] [Google Scholar]
70. Burton GJ, Jauniaux East, Watson AL. Maternal arterial connections to the placental intervillous space during the start trimester of human pregnancy: The Boyd collection revisited. Am J Obstet Gynecol. 1999;181:718–724. [PubMed] [Google Scholar]
71. Hustin J, Schaaps JP. Echographic and anatomic studies of the maternotrophoblastic border during the first trimester of pregnancy. Am J Obstet Gynecol. 1987;157:162–168. [PubMed] [Google Scholar]
72. Jauniaux East, Jurkovic D, Campbell S. In vivo investigation of the placental circulations by Doppler echography. Placenta. 1995;xvi:323–331. [PubMed] [Google Scholar]
73. Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ. Onset of maternal arterial blood menses and placental oxidative stress: A possible factor in human early pregnancy failure. Am J Pathol. 2000;157:2111–2122. [PMC free article] [PubMed] [Google Scholar]
74. Avarez-Silva 1000, Belo-Diabangouaya P, Salaun J, Dieterlen-Lievre F. Mouse placenta is a major hematopoietic organ. Development. 2003;130:5437–5444. [PubMed] [Google Scholar]
75. Gekas C, eterlen-Lievre F, Orkin SH, Mikkola HK. The placenta is a niche for hematopoietic stem cells. Dev Prison cell. 2005;8:365–375. [PubMed] [Google Scholar]
76. Ottersbach Grand, Dzierzak Due east. The murine placenta contains hematopoietic stem cells inside the vascular labyrinth region. Dev Cell. 2005;8:377–387. [PubMed] [Google Scholar]
77. Guetta E, Gordon D, Simchen MJ, Goldman B, Barkai Thousand. Hematopoietic progenitor cells as targets for non-invasive prenatal diagnosis: Detection of fetal CD34+ cells and assessment of post-commitment persistence in the maternal circulation. Claret Cells Mol Dis. 2003;30:13–21. [PubMed] [Google Scholar]
78. Lambert NC, Pang JM, Yan Z, Erickson TD, Stevens AM, Furst DE, Nelson JL. Male microchimerism in women with systemic sclerosis and salubrious women who have never given nativity to a son. Ann Rheum Dis. 2005;64:845–848. [PMC free article] [PubMed] [Google Scholar]
79. Yan Z, Lambert NC, Guthrie KA, Porter AJ, Loubiere LS, Madeleine MM, Stevens AM, Hermes HM, Nelson JL. Male microchimerism in women without sons: Quantitative assessment and correlation with pregnancy history. Am J Med. 2005;118:899–906. [PubMed] [Google Scholar]
fourscore. Guettier C, Sebagh Yard, Buard J, Feneux D, Ortin-Serrano One thousand, Gigou M, Tricottet V, Reynes Thousand, Samuel D, Feray C. Male person prison cell microchimerism in normal and diseased female livers from fetal life to adulthood. Hepatology. 2005;42:35–43. [PubMed] [Google Scholar]
81. Landy HJ, Keith LG. The vanishing twin: A review. Hum Reprod Update. 1998;4:177–183. [PubMed] [Google Scholar]
82. Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update. 2003;9:347–357. [PubMed] [Google Scholar]
83. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: Hiding in plain sight. Immunol Rev. 2006;213:48–65. [PMC free article] [PubMed] [Google Scholar]
84. Bainbridge DR. Evolution of mammalian pregnancy in the presence of the maternal allowed system. Rev Reprod. 2000;5:67–74. [PubMed] [Google Scholar]
85. Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW. The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review. Arthritis Rheum. 2003;48:3237–3241. [PubMed] [Google Scholar]
86. Bianchi DW. Fetal cells in the mother: From genetic diagnosis to diseases associated with fetal cell microchimerism. Eur J Obstet Gynecol Reprod Biol. 2000;92:103–108. [PubMed] [Google Scholar]
87. Bianchi DW. Fetomaternal jail cell trafficking: A new cause of disease? Am J Med Genet. 2000;91:22–28. [PubMed] [Google Scholar]
88. Nelson JL. Microchimerism: Incidental byproduct of pregnancy or active participant in human health? Trends Mol Med. 2002;8:109–113. [PubMed] [Google Scholar]
89. Nelson JL. Microchimerism and human autoimmune diseases. Lupus. 2002;11:651–654. [PubMed] [Google Scholar]
ninety. Nelson JL. Microchimerism in human being wellness and disease. Autoimmunity. 2003;36:v–ix. [PubMed] [Google Scholar]
91. Bianchi DW. Fetomaternal cell traffic, pregnancy-associated progenitor cells, and autoimmune disease. All-time Pract Res Clin Obstet Gynaecol. 2004;18:959–975. [PubMed] [Google Scholar]
92. Johnson KL, Bianchi DW. Fetal cells in maternal tissue following pregnancy: What are the consequences? Hum Reprod Update. 2004;10:497–502. [PubMed] [Google Scholar]
93. Johnson KL, Samura O, Nelson JL, McDonnell Grand, Bianchi DW. Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: Evidence of long-term survival and expansion. Hepatology. 2002;36:1295–1297. [PubMed] [Google Scholar]
94. Cha D, Khosrotehrani Grand, Kim Y, Stroh H, Bianchi DW, Johnson KL. Cervical cancer and microchimerism. Obstet Gynecol. 2003;102:774–781. [PubMed] [Google Scholar]
95. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA. 2004;292:75–80. [PubMed] [Google Scholar]
96. Kremer Hovinga I, Koopmans Yard, de HE, Bruijn JA, Bajema IM. Chimerism in systemic lupus erythematosus-iii hypotheses. Rheumatology (Oxford) 2007;46:200–208. [PubMed] [Google Scholar]
97. Mosca M, Curcio M, Lapi S, Valentini Thou, D'Angelo S, Rizzo 1000, Bombardieri South. Correlations of Y chromosome microchimerism with affliction action in patients with SLE: Analysis of preliminary data. Ann Rheum Dis. 2003;62:651–654. [PMC free article] [PubMed] [Google Scholar]
98. Huu SN, Oster Chiliad, Uzan Southward, Chareyre F, Aractingi S, Khosrotehrani K. Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells. Proc Natl Acad Sci United states of america. 2007;104:1871–1876. [PMC free article] [PubMed] [Google Scholar]
99. Evans PC, Lambert Northward, Maloney S, Furst DE, Moore JM, Nelson JL. Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood. 1999;93:2033–2037. [PubMed] [Google Scholar]
100. Huu SN, Dubernard One thousand, Aractingi South, Khosrotehrani K. Feto-maternal prison cell trafficking: A transfer of pregnancy associated progenitor cells. Stem Cell Rev. 2006;ii:111–116. [PubMed] [Google Scholar]
101. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer M, Lois C, Morrison SJ, Alvarez-Buylla A. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 2003;425:968–973. [PubMed] [Google Scholar]
102. Osada H, Doi South, Fukushima T, Nakauchi H, Seki K, Sekiya S. Detection of fetal HPCs in maternal circulation after delivery. Transfusion. 2001;41:499–503. [PubMed] [Google Scholar]
103. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stalk/progenitor cells in homo commencement-trimester fetal blood, liver, and os marrow. Blood. 2001;98:2396–2402. [PubMed] [Google Scholar]
104. Rossi G. Nature of stalk cell involved in fetomaternal microchimerism. Lancet. 2004;364:1936. [PubMed] [Google Scholar]
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633676/
0 Response to "If a Woman Is Pregnant and Has Intercourse With Different Man Can the Baby Absorb His Traits"
Publicar un comentario