Wlodek M E, Koutsis K, Westcott K T, Ho P W, Di Nicolantonio R, Moseley J M
Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.
Placenta. 2001 Aug;22(7):646-51. doi: 10.1053/plac.2001.0699.
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.
与正常血压对照的Wistar Kyoto(WKY)大鼠相比,自发性高血压大鼠(SHR)的宫内甲状旁腺激素相关蛋白(PTHrP)浓度降低,且与生长受限有关,这表明PTHrP是一种关键的胎儿生长因子。本研究的目的是通过SHR和WKY之间的胚胎交叉移植,研究是母亲、胎儿还是两者共同导致了SHR羊水PTHrP的抑制。将1日龄的SHR胚胎在SHR(SHR-in-SHR)或WKY(SHR-in-WKY)代孕母体中孕育,同样,将1日龄的WKY胚胎在SHR(WKY-in-SHR)或WKY(WKY-in-WKY)母体中孕育。妊娠20天时,采集母体血浆和羊水样本,检测PTHrP浓度。数据采用双向方差分析(均值±标准误,每组n = 5 - 9只母鼠)。窝仔数或母体血浆PTHrP浓度无差异。与WKY胎儿相比,无论母体品系如何,SHR胎儿的体重(P < 0.009)、胎儿/胎盘重量比(P < 0.004)和羊水PTHrP浓度(P < 0.001)较低,而羊水量(P < 0.0001)较高。因此,SHR胎儿生长受限且羊水PTHrP受到抑制,这在很大程度上由胎儿或妊娠组织决定,与母体高血压或母体PTHrP无关。我们认为,SHR羊水PTHrP水平低可能在SHR生长受限的发生中起作用。