Journal of Immunology vol:178 issue:7 pages:4267-4275
Placenta growth factor (PIGF; 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 PIGF 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 PIGF antagonist sFIt-1 or S-endoglin induces pre-eclampsia-like lesions. Mice genetically deleted in PIGF 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 (136) mice with immunohistology to analyze PIGF expression in normal mouse pregnancy. To estimate the significance of uNK cell-derived PIGF, PIGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 nult/common gamma chain null mice and in laser capture-microdissected B6 uNK cells. Histopathologic consequences from PIGF deletion were also characterized in the implantation sites from PIGF null mice. In B6, decidual PIGF expression rose between gd8-16. uNK cells were among several types of cells transcribing PIGF in decidualized endometrium. Immature uNK cells, defined by their low numbers, p of cytoplasmic granules, were the uNK cells displaying the greatest number of transcripts. PIGF 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, PIGF plays an important role in successful uNK cell proliferation and/or differentiation.