School of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, Queensland, Australia.
School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Sci Rep. 2017 Aug 15;7(1):8241. doi: 10.1038/s41598-017-08365-4.
Prenatal hypoxia is associated with growth restriction and adverse cardiovascular outcomes. Here, we describe renal and cardiovascular outcomes in ageing mouse offspring prenatally exposed to hypoxia (12% O) from embryonic day 14.5 until birth. At 12 months of age, both male and female offspring exposed to prenatal hypoxia had elevated mean arterial pressure. Glomerular number was reduced by 25% in hypoxia-exposed male, but not female, offspring and this was associated with increased urinary albumin excretion, glomerular hypertrophy and renal fibrosis. Hypoxia-exposed offspring of both sexes were more susceptible to salt-induced cardiac fibrosis, however, renal fibrosis was exacerbated by high salt in males only. In male but not female hypoxia-exposed offspring, renal renin mRNA was increased at weaning. By 12 months, renal renin mRNA expression and concentrations were elevated in both sexes. mRNA expression of At R was also elevated in male hypoxia-exposed offspring at 12 months. These results demonstrate that prenatal hypoxia programs elevated blood pressure and exacerbates salt-induced cardiovascular and renal pathology in a sex specific manner. Given sex differences observed in RAS expression and nephron number, future studies may consider RAS blockade as a therapeutic target in this model.
产前缺氧与生长受限和不良心血管结局有关。在这里，我们描述了从胚胎第 14.5 天到出生为止，在产前缺氧（12% O）环境下暴露的老鼠后代的肾脏和心血管结局。在 12 个月大时，暴露于产前缺氧的雄性和雌性后代的平均动脉压均升高。在雄性而不是雌性缺氧暴露的后代中，肾小球数量减少了 25%，这与尿白蛋白排泄增加、肾小球肥大和肾纤维化有关。两性缺氧暴露的后代对盐诱导的心脏纤维化更敏感，但只有雄性的肾脏纤维化会因高盐而加剧。在雄性但不是雌性的缺氧暴露后代中，断奶时肾脏肾素 mRNA 增加。到 12 个月时，两性的肾脏肾素 mRNA 表达和浓度均升高。在 12 个月时，雄性缺氧暴露的后代的 At1R mRNA 表达也升高。这些结果表明，产前缺氧以性别特异性的方式编程高血压，并加重盐诱导的心血管和肾脏病理。鉴于在 RAS 表达和肾单位数量方面观察到的性别差异，未来的研究可能会考虑在该模型中使用 RAS 阻断作为治疗靶点。
