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* Department of Biomedical Sciences and
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada;
Center for Transgene Technology, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium; and
Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada
Placenta growth factor (PlGF; formerly PGF), a vascular endothelial growth factor gene family member, is expressed in human implantation sites by maternal uterine NK (uNK) and fetal trophoblast cells. Lower than normal concentrations of blood and urinary PlGF have been associated with impending onset of pre-eclampsia, a hypertensive disease of late human gestation characterized by limited intravascular trophoblast invasion. In pregnant rodents, delivery of the PlGF antagonist sFlt-1 or S-endoglin induces pre-eclampsia-like lesions. Mice genetically deleted in PlGF reproduce, but neither their implantation sites nor their uNK cell development are described. We combined real-time PCR of endometrium from nonpregnant and gestation day (gd)6–18 C57BL6/J (B6) mice with immunohistology to analyze PlGF expression in normal mouse pregnancy. To estimate the significance of uNK cell-derived PlGF, PlGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 null/common 
chain null mice and in laser capture-microdissected B6 uNK cells. Histopathologic consequences from PlGF deletion were also characterized in the implantation sites from PlGF null mice. In B6, decidual PlGF expression rose between gd8–16. uNK cells were among several types of cells transcribing PlGF in decidualized endometrium. Immature uNK cells, defined by their low numbers of cytoplasmic granules, were the uNK cells displaying the greatest number of transcripts. PlGF deletion promoted the early differentiation high numbers of binucleate uNK cells (gd8) but had no other significant, morphometrically detectable impact on implantation sites. Thus, in mice, PlGF plays an important role in successful uNK cell proliferation and/or differentiation.
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1 Address correspondence and reprint requests to Dr. Chandrakant Tayade, Department of Biomedical Sciences, University of Guelph, Guelph, Ontario Canada. E-mail address: ctayade{at}uoguelph.ca
2 Abbreviations used in this paper: PlGF, placenta growth factor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; uNK, uterine NK; PL, placenta; gd, gestation day; MLAp, mesometrial lymphoid aggregate of pregnancy; c, common -chain; LCM, laser capture microdissection; DB, decidua basalis; DBA, Dolichos biflorus agglutinin; AG, agranular; IM, immature; aRNA, antisense RNA; PAS, periodic acid-Schiff; WT, wild type.
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