Abstract
Placental growth factor (PlGF) is decreased in early gestation of pregnant women who subsequently develop pre-eclampsia. In this study, pre-emptive treatment with PlGF to prevent pre-eclampsia was evaluated in an in vivo rodent model of experimental pre-eclampsia (EPE) induced by TNF-α and in an in vitro model of human first-trimester trophoblast invasion. Pregnant C57/BL6 mice were treated with recombinant mouse placental growth factor-2 (rmPlGF-2) 100 μg/kg/day IP from gestational day (gd) 10. Animals had EPE induced by continuous TNF-α infusion on gd 13 and were subject to either continuous blood pressure monitoring by radiotelemetry throughout pregnancy or live placenta T2-weighted magnetic resonance imaging (MRI) to demonstrate placental function on gd 17. There was no difference in BP (P > .99), proteinuria (P =.9) or T2 values on MRI (P =.9) between control and rmPlGF-2-treated animals. On gd 13, animals treated with rmPlGF-2 demonstrated increased placenta PlGF (P =.01) and Toll-like receptor-3 (P =.03) mRNA expression as compared with controls. Fluorescent-labelled human uterine microvascular endothelial cells and HTR8/SVNeo cells were co-cultured on Matrigel™ and treated with recombinant human PlGF (rhPlGF) (10 ng/mL) and/or TNF-α (0.5 ng/mL). Trophoblast integration into endothelial networks was reduced by added TNF-α (P =.006), as was rhPlGF concentration in conditioned media (P < .0001). Cell integration was not ameliorated by addition of rhPlGF (P > .9). Although TNF-α-induced EPE was not reversed with pre-emptive rmPlGF-2, a further trial of pre-emptive rhPlGF in vivo is required to determine whether the absence of effect of rhPlGF demonstrated in vitro precludes PlGF as a preventative therapy for pre-eclampsia.
Original language | English |
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Pages (from-to) | 49-59 |
Number of pages | 11 |
Journal | Clinical and Experimental Pharmacology and Physiology |
Volume | 47 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- abnormalities
- placenta
- preeclampsia
- pregnant women
- trophoblast