Expression of the colony stimulating factor-1 receptor (c-fms product) by cells at the human uteroplacental interface.
BACKGROUND
The hematopoietic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (encoded by the proto-oncogene c-fms) are implicated in the regulation of human placental development.


METHODS
In this study, we have performed a detailed immunohistochemical localization of the CSF-1 receptor (CSF-1R) on cells of the uteroplacental interface in human first trimester pregnancy, supplemented by Northern blot, in situ hybridization, and flow cytometric analysis. CSF-1R expression by JEG-3 and JAR choriocarcinoma cells was also investigated.


RESULTS
c-fms mRNA was detected in primary cultures of first trimester trophoblast and was localized to the extravillous cytotrophoblast columns streaming off the anchoring villi. CSF-1R was expressed by fetal Hofbauer cells in the mesenchyme of the chorionic villi, and this expression increased considerably from first trimester to term. No expression was seen on first trimester and term villous cytotrophoblast. CSF-1R expression on villous syncytiotrophoblast was absent at 6 weeks, strongest at 8-10 weeks, and faded by 12 weeks. First trimester extravillous cytotrophoblast columns were strongly and consistently positive for CSF-1R expression, as was the superficial shell of extravillous trophoblast over the maternal decidua. However, with deeper invasion and terminal differentiation into placental bed giant cells, this expression became weak or absent. Endovascular trophoblast was also only weakly positive for CSF-1R. At the implantation site itself, large numbers of decidual macrophages and CD3-, CD56bright large granular lymphocytes were seen. The macrophages expressed CSF-1R strongly, but large granular lymphocytes, decidual stromal cells, glandular epithelium, and endothelial cells were found to be negative for CSF-1R expression. No CSF-1R expression was detected in JAR choriocarcinoma cells, but CSF-1R was present in first trimester cultured trophoblast and JEG-3 choriocarcinoma cells, although this was shown to be intracellular.


CONCLUSIONS
These results suggest that CSF-1 may regulate invasion and differentiation of human placental trophoblast, depending upon the spatial and temporal distribution of its receptor. CSF-1 may also influence placental development and function by acting via decidual and fetal macrophages, which are the other cell populations expressing the receptor.
Jokhi
P P
PP
Department of Pathology, University of Cambridge, United Kingdom.
Chumbley
G
G
King
A
A
Gardner
L
L
Loke
Y W
YW
D015152:Blotting, Northern; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D002824:Chorionic Villi / Q000737:chemistry / Q000648:ultrastructure; D004247:DNA / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D003656:Decidua / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000502:physiology / Q000648:ultrastructure; D010920:Placenta / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D014599:Uterus / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D004247:DNA; D016186:Receptor, Macrophage Colony-Stimulating Factor