Elsevier

Placenta

Volume 26, Issue 4, April 2005, Pages 282-288
Placenta

Immunocytological evidence for hematopoiesis in the early human placenta

https://doi.org/10.1016/j.placenta.2004.06.007Get rights and content

Abstract

Hematopoiesis has previously been observed in the human yolk sac, in placental villi and in the embryonic aorta. Here, our immunocytological study at 24 and 35 days showed packed erythroblasts in the placental vessels, mitotic figures and anti-Ki-67 reactions within these cells. Morphologically, the erythroblasts and vessels were similar to those found in the yolk sac during primitive hematopoiesis. In addition, numerous extravascular erythroblasts were found in the villous core. Positive reactions were obtained in erythroblasts using antibodies against glycophorin-A, GATA-2 and C-kit that characterize the hematopoietic cells. However, erythroblasts did not react with anti-CD34 and anti-CD45. In this respect, they differ from the hematopoietic cell clusters observed in the aorta of the human embryo. The staining for glycophorin-A was maintained in erythroblasts at 6–7 weeks and 12–14 weeks. Anti-GATA-2 reaction was decreased in erythroblasts and appeared in the perivillous cytotrophoblast. Anti-C-kit signal was detected in endothelial cells at 6–7 weeks and switched to stromal and perivascular cells at 12–14 weeks. By term, anti-GATA-2 staining was still present in the trophoblast and appeared in vessels while anti-C-kit was negative. For the leukocytes marker CD15, a staining was found in the endothelium at 35 days, 6–7 and 12–14 weeks and in leukocytes at term. CD45 antibody decorated the leukocytes at 12–14 weeks and at term. Erythroblasts undergo a primitive hematopoiesis in the early placental vessels that may be of value for the embryo in a period of low oxygen environment.

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.

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