Infusion of exogenous platelet-activating factor produces intrauterine growth restriction in the rat.

Abstract

To determine the impact of exogenous platelet-activating factor (PAF) on pregnancy outcome in the rat. Carbamyl-PAF (0.05, 0.5, or 5.0 microg/kg per hour) or vehicle was infused intravenously for 7 days by osmotic pump into timed pregnant rats. Infusion was begun on day 14 of a 22-day gestation. Maternal mean arterial blood pressures were measured on days 1, 4, and 7 of the infusion. On gestational day 21 (PAF infusion day 7), fetal and placental weights and viability were evaluated at hysterotomy. Uterine and placental PAF receptor expression was analyzed by reverse transcription-polymerase chain reaction and agarose gel electrophoresis. Data were analyzed by analysis of variance, chi(2), or the Mann-Whitney U test as appropriate. Fetal weights were dose-dependently lower than control, by 19% and 35%, respectively, at dosages of 0.5 and 5.0 microg/kg per hour (P < .001) but were not affected at the 0.05 microg/kg per hour dose of carbamyl-PAF. Placental weights were significantly lower at all doses (P < .001). Fetal demise was dose-dependently higher and was significantly different from the control group at the 0.5 and 5.0 microg/kg per hour doses of carbamyl-PAF (P < .0001). Maternal mean arterial pressures were not altered by these doses of carbamyl-PAF. PAF receptors were expressed abundantly in both uterus and placenta. Exogenous PAF produces dose-dependent fetal growth restriction in the rat. Placental growth is particularly sensitive to PAF and, coupled with the dose-dependent decline in fetal growth, suggests a dose-dependent decline in function. An elevated level of PAF is detrimental to fetal growth and well-being in the rat.