Placental hypoxia during placental malaria.
BACKGROUND
Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR.


METHODS
We studied the hypoxia markers hypoxia inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), placental growth factor, VEGF receptor 1 and its soluble form, and VEGF receptor 2. We used real-time polymerase chain reaction (in 59 women) to examine gene transcription, immunohistochemistry (in 30 women) to describe protein expression, and laser-capture microdissection (in 23 women) to examine syncytiotrophoblast-specific changes in gene expression. We compared gene and protein expression in relation to malaria infection, monocyte infiltrates, and birth weight.


RESULTS
We could not associate any hallmark of placental malaria with a transcription, expression, or tissue-distribution profile characteristic of a response to hypoxia, but we found higher HIF-1alpha levels (P= .0005) and lower VEGF levels (P= .0026) in the syncytiotrophoblasts of cases of malaria than in those of asymptomatic control placentas.


CONCLUSIONS
Our data are inconsistent with a role for placental hypoxia in the pathogenesis of malaria-associated FGR. The laser-capture microdissection study was small, but its results suggest (1) that malaria affects syncytiotrophoblast-gene transcription and (2) novel potential mechanisms for placental malaria-associated FGR.
Boeuf
Philippe
P
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. pboeuf@unimelb.edu.au
Tan
Aimee
A
Romagosa
Cleofe
C
Radford
Jane
J
Mwapasa
Victor
V
Molyneux
Malcolm E
ME
Meshnick
Steven R
SR
Hunt
Nicholas H
NH
Rogerson
Stephen J
SJ
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002824:Chorionic Villi / Q000378:metabolism / Q000469:parasitology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000469:parasitology*; D005311:Fetal Hypoxia / Q000469:parasitology*; D020869:Gene Expression Profiling; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008288:Malaria / Q000150:complications*; D009000:Monocytes / Q000469:parasitology / Q000473:pathology; D010920:Placenta / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D000072483:Placenta Growth Factor; D010965:Plasmodium malariae / Q000472:pathogenicity*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000503:physiopathology*; D011257:Pregnancy Proteins / Q000378:metabolism; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2