Immunocytological evidence for hematopoiesis in the early human placenta
Introduction
Hematopoiesis was first observed in the human yolk sac at day 18.5 of pregnancy [1]. Subsequently, a cluster of CD34+ cells was described at the floor of the aorta in 5 week human embryos [2] and these cells were also positive to CD45 antibody. They cross-reacted with other endothelial markers such as CD31 but were negative to lectin UEA-1. The capacity of these extra- and intra-embryonic areas for providing pluripotent stem cells colonizing the liver has been debated. The yolk sac precedes the para-aortic area in generating hematopoietic cells, however, its capacity for giving rise to lymphoid cell lines in culture seems limited compared with that of the para-aortic area [3]. Therefore, aortic and para-aortic areas could be major sites for the supply of hematogenous precursors. Other extraembryonic areas could be involved in hematopoiesis as a recent investigation has shown that the allantois could be another site for the development of hematopoietic stem cells in the chick [4].
The mouse placenta has been recently implicated in hematopoiesis [5]. Placental hematopoiesis has been also suggested for the marmoset placenta on the basis of an ultrastructural study [6]. Hematopoietic stem cells have been previously described in the human placental villi by transmission electron microscopy [7]. Although placental hematopoiesis in humans from day 28 post-conception onwards is accepted by placentologists, it has not been evaluated thoroughly. Recent investigations on human placental vessels showed that they are fairly well differentiated at 6 weeks post-menstruation (4 weeks post-conception), exhibiting α-sm-actin, CD31, D34, V/E-cadherin, α3 and α5 integrin subunits but acquiring binding sites for antibodies against UEA-1-lectin and sm-myosins later [8]. Erythroblasts were observed in these vessels at 6 weeks of pregnancy, reticulocytes came later at 12–14 weeks [9].
We investigated the possibility of placental hematopoiesis in the human placenta samples from day 24 to 12–14 weeks post-conception. We performed histological and immunocytochemical examinations on tissue samples from spontaneous abortions, tubal pregnancy and voluntary terminations of pregnancy. For the histology, we focused our attention on placental vessels, erythroblasts and figures of mitosis. For the immunocytochemistry, we selected antibodies detecting erythroblasts (glycophorin-A), cells within the cell cycle (Ki-67 antigen), leukocytes (CD15, CD45) and hematopoietic markers (GATA-2, C-kit). Our study suggests that an active placental hematopoiesis occurs in early pregnancy, based on the presence of blood islands in the villi, on mitosis and the detection of hematopoietic markers in erythroblasts.
Section snippets
Material and methods
The placentas studied were from one case of spontaneous abortion due to an inflammatory reaction of the decidua, addressed to the Institute of Histo-Cyto-Pathology (Bordeaux, France) for examination, with an embryo of 4 mm length at 35–36 days post-conception, normally developed, and from one case of tubal pregnancy with an embryo of 3 mm length estimated to be at 24–25 days post-conception. Placental tissues were also obtained after voluntary termination of normal pregnancy. The patients were
24–35 days of pregnancy
In the sections of 35–36 day villi, hematoxylin–eosin–saffron staining showed many vessels surrounded by a thin endothelial layer. The lumen of many vessels was filled by packed erythroblasts (Figure 1). These arrangements were also observed in other spontaneous abortions, tubal pregnancies, and voluntary terminations of pregnancy at 6–7 weeks (not shown). The antibody against Glyc-A labelled the cell membrane of erythroblasts, not the thin endothelial layer. Some of the erythroblasts were
Discussion
The human placenta on day 25 of pregnancy showed typical figures of hematopoiesis comparable to those described for the yolk sac of the human embryo [1], [10] and for the mesoderm of area opaca of the 4–11 somite chick embryo [11]. Clumps of tightly packed erythroblasts completely filled the vascular lumen. Numerous erythroblasts had entered the cell cycle as indicated by the Ki-67 labelling, or in mitosis exhibiting prophasic nuclei, metaphasic or telophasic figures. These observations
Acknowledgements
We are indebted to the staffs of Saint Vincent de Paul Hospital (Dr Sophie Gaudu, Dr Jacques Lepercq) and Tenon Hospital (Dr Gil Dubernard, Dr Philippe Merviel) for their kind assistance. We also thank Dr Françoise Ferré (INSERM U361, Paris) and Dr Sylvie Hauguel-de Mouzon (Case Western Reserve University, Cleveland) for their support in this research program.
References (25)
- et al.
Aorta-associated CD34+ hematopoietic cells in the early human embryo
Blood
(1996) - et al.
The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: mapping multipotent hematopoietic cell fate in intraembryonic mesoderm
Immunity
(2001) - et al.
Hemangioblast commitment in the avian allantois: cellular and molecular aspects
Dev Biol
(2001) Molecular aspects of embryonic hemoglobin function
Mol Aspects Med
(2002)- et al.
Localization of stem cell factor (SCF) and c-kit mRNA in human placental tissue and biological effects of SCF on DNA synthesis in primary cultured cytotrophoblasts
Biochem Biophys Res Commun
(1994) - et al.
Leukocyte-endothelial adhesion molecules
Blood
(1994) - et al.
Hematopoiesis in young human embryo
Am J Anat
(1940) - et al.
Mouse placenta is a major hematopoietic organ
Development
(2003) - et al.
Fine structural observations on hematopoiesis in the chorioallantoic placenta of the marmoset
Am J Anat
(1975) - et al.
Fetal vasculogenesis and angiogenesis in human placental villi
Acta Anat (Basel)
(1989)
Characterization of first trimester human fetal placental vessels using immunocytochemical markers
Cell Mol Biol
Separation of trophoblastic and vascular cell lineages and vascular maturation in early human placental development
Cell Mol Biol
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