The Spontaneously Hypertensive Rat Fetus, Not the Mother, is Responsible for the Reduced Amniotic Fluid PTHrP Concentrations and Growth Restriction

Abstract

Intrauterine parathyroid hormone-related protein (PTHrP) concentrations are reduced in association with growth restriction in the spontaneously hypertensive rat (SHR) compared to those of its normotensive control, the Wistar Kyoto (WKY) rat, implicating PTHrP as a pivotal fetal growth factor. The aim of this study was to examine, by embryo cross-transplanation between SHR and WKY, whether the mother, fetus, or both, are responsible for the suppressed SHR amniotic fluid PTHrP. One-day-old SHR embryos were gestated in either an SHR (SHR-in-SHR) or WKY (SHR-in-WKY) surrogate, similarly one-day-old WKY embryos were gestated in either an SHR (WKY-in-SHR) or WKY (WKY-in-WKY) mother. At 20 days gestation, maternal plasma and amniotic fluid samples were collected and assayed for PTHrP concentrations. Data were analysed by two-way ANOVA (mean±sem,n =5–9 mothers/group). There were no differences in litter number or maternal plasma PTHrP concentrations. Fetal weight (P< 0.009), fetal/placental weight ratio (P< 0.004) and amniotic fluid PTHrP concentrations (P< 0.001) were lower and amniotic fluid volume (P< 0.0001) was higher with an SHR fetus compared to the WKY fetus irrespective of maternal strain. Thus, the SHR fetus is growth restricted and has suppressed amniotic fluid PTHrP, which are largely determined by the fetus or gestational tissues and are independent of maternal hypertension or maternal PTHrP. We suggest that the low SHR amniotic fluid PTHrP may play a role in the development of SHR growth restriction.