Prenatal exposure to glucocorticoids (GC) is a central topic of interest in medicine since GCs are essential for the maturation of fetal organs and intrauterine growth. Synthetic glucocorticoids, which are used in obstetric practice, exert beneficial effects on the fetus, but have also been reported to lead to intrauterine growth retardation (IUGR). In this study, a model of growth restriction in mice was established through maternal administration of dexamethasone during late gestation. We hypothesised that GC overexposure may adversely affect placental angiogenesis and fetal and placental growth. Female BALB/c mice were randomly assigned to control or dexamethasone treatment, either left to give birth or euthanised on days 15, 16, 17 and 18 of gestation followed by collection of maternal and fetal tissue. The IUGR rate increased to 100% in the dexamethasone group (8 mg/kg body weight on gestational days 14 and 15) and pups had clinical features of symmetrical IUGR at birth. Dexamethasone administration significantly decreased maternal body weight gain and serum corticosterone levels. Moreover, prenatal dexamethasone treatment not only induced fetal growth retardation but also decreased placental weight. In IUGR placentas, VEGFA protein levels and mRNA expression of VEGF receptors were reduced and NOS activity was lower. Maternal dexamethasone administration also reduced placental expression of the GC receptor, αGR. We demonstrated that maternal dexamethasone administration causes fetal and placental growth restriction. Furthermore, we propose that the growth retardation induced by prenatal GC overexposure may be caused, at least partially, by an altered placental angiogenic profile.

中文翻译：

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地塞米松诱导的宫内生长受限调节胎盘血管生长因子的表达以及胎儿和胎盘的生长


产前接触糖皮质激素 (GC) 是医学界关注的一个中心话题，因为 GC 对于胎儿器官的成熟和宫内生长至关重要。产科实践中使用的合成糖皮质激素对胎儿产生有益影响，但也有报道称会导致宫内生长迟缓 (IUGR)。在这项研究中，通过在妊娠后期母亲给予地塞米松来建立小鼠生长受限模型。我们假设 GC 过度暴露可能会对胎盘血管生成以及胎儿和胎盘生长产生不利影响。雌性 BALB/c 小鼠被随机分配至对照组或地塞米松治疗组，要么留置分娩，要么在妊娠第 15、16、17 和 18 天实施安乐死，然后收集母体和胎儿组织。地塞米松组（妊娠第14天和第15天8毫克/公斤体重）的IUGR率增加至100%，并且幼仔出生时具有对称IUGR的临床特征。地塞米松给药显着降低了母亲的体重增加和血清皮质酮水平。此外，产前地塞米松治疗不仅会导致胎儿生长迟缓，还会降低胎盘重量。在IUGR胎盘中，VEGFA蛋白水平和VEGF受体mRNA表达降低，NOS活性降低。母亲给予地塞米松也减少了 GC 受体 αGR 的胎盘表达。我们证明，母亲给予地塞米松会导致胎儿和胎盘生长受限。此外，我们认为，产前 GC 过度暴露引起的生长迟缓可能至少部分是由胎盘血管生成谱的改变引起的。