96. Effect of preventative treatment with placental growth factor-2 on experimental preeclampsia induced by TNF-α in pregnant mice

Introduction Placental growth factor (PlGF) is deficient in women with preeclampsia and treatment of experimental preeclampsia (EPE) with parenteral PlGF has been successful in animal models. Abnormal placentation is thought to be the initiating event in the pathogenesis of preeclampsia and this process may be mediated by PlGF. Objective To evaluate the effect of preventative treatment with PlGF-2 in pregnant mice with EPE induced by tumour necrosis factor- α (TNF- α ) infusion. Methods C57/BL6 mice were treated with daily PlGF-2 (100 ng/kg) or control (phosphate buffered saline 100 uL) intraperitoneally from gestational day (gd) 10 onward. Mice were allocated to one of 3 experimental arms: 1) Animals (n  = 5 per group) were euthanised on gd13 to assess the effect of PlGF-2 in early pregnancy; 2) Animals (n  = 5 per group) had EPE induced by continuous TNF- α (500 ng/kg/day) infusion. These animals had continuous blood pressure (BP) measurement by radiotelemetry device inserted a minimum 10 days prior to timed mating; 3) Animals (n  = 3 per group) had EPE induced as above and live placenta magnetic resonance imaging (MRI) in an 11.74 Tesla spectrometer on gd17. Animals in arm 2 and 3 were euthanized at gd17 and blood, urine and tissue samples were collected. Data was analysed with GraphPad Prism 7. Results PlGF-2 animals euthanised at gd13 demonstrated increased placenta PlGF (p  = 0.01) and toll like receptor-3 (TLR-3) (p  = 0.03) mRNA expression as compared with controls. In animals with EPE there was no difference in BP (p = 0.7) or proteinuria (p > 0.9) between control and PLGF-2 treated animals. There was no difference in T2 labyrinthine/junctional zone ratio in mouse placentas imaged (p  = 0.9). Discussion Preventative treatment with PlGF-2 altered expression of PlGF and TLR-3 but did not ameliorate features of EPE or placental perfusion as assessed by live MRI.