School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
Priority Research Centre for Reproductive Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
Reproduction. 2019 Sep;158(3):237-245. doi: 10.1530/REP-18-0633.
Fetal growth restriction (FGR) is a pregnancy complication wherein the foetus fails to reach its growth potential. The renin-angiotensin system (RAS) is a critical regulator of placental function, controlling trophoblast proliferation, angiogenesis and blood flow. The RAS significantly influences uteroplacental blood flow through the balance of its vasoconstrictive and vasodilatory pathways. Although the RAS is known to be dysregulated in placentae from women with preeclampsia, the expression of the RAS has not yet been studied in pregnancies compromised by FGR alone. This study investigated the mRNA expression and protein levels of RAS components in placentae from pregnancies compromised by FGR. Angiotensin II type 1 receptor (AGTR1) and angiotensin-converting enzyme 2 (ACE2) mRNA levels were reduced in FGR placentae compared with control (P = 0.012 and 0.018 respectively). Neprilysin (NEP) mRNA expression was lower in FGR placentae compared with control (P = 0.004). mRNA levels of angiotensinogen (AGT) tended to be higher in FGR placentae compared with control (P = 0.090). Expression of prorenin, AGT, angiotensin-converting enzyme (ACE) or ACE2 proteins were similar in control and FGR placentae. The renin-AGT reaction is a first order reaction so levels of expression of placental AGT determine levels of Ang II. Decreasing levels of ACE2 and/or NEP by limiting the production of Ang-(1-7), which is a vasodilator, and increasing placental Ang II levels (vasoconstrictor) may result in an imbalance between the vasoconstrictor and vasodilator arms of the placental RAS. Ultimately this dysregulation of the placental RAS could lead to reduced placental perfusion that is evident in FGR.
胎儿生长受限（FGR）是一种妊娠并发症，其中胎儿未能达到其生长潜力。肾素-血管紧张素系统（RAS）是胎盘功能的关键调节剂，控制滋养细胞增殖、血管生成和血流。RAS 通过其血管收缩和血管舒张途径的平衡显著影响子宫胎盘血流。尽管已知 RAS 在患有子痫前期的妇女的胎盘中失调，但 RAS 的表达尚未在单独由 FGR 引起的妊娠中进行研究。本研究调查了由 FGR 引起的妊娠中胎盘 RAS 成分的 mRNA 表达和蛋白水平。与对照组相比，FGR 胎盘的血管紧张素 II 型 1 受体（AGTR1）和血管紧张素转换酶 2（ACE2）mRNA 水平降低（分别为 P = 0.012 和 0.018）。Neprilysin（NEP）mRNA 表达在 FGR 胎盘与对照组相比降低（P = 0.004）。与对照组相比，FGR 胎盘的血管紧张素原（AGT）mRNA 水平趋于升高（P = 0.090）。控和 FGR 胎盘的 prorenin、AGT、血管紧张素转换酶（ACE）或 ACE2 蛋白的表达相似。肾素-血管紧张素原反应是一级反应，因此胎盘 AGT 的表达水平决定了 Ang II 的水平。通过限制血管舒张素 Ang-（1-7）的产生来降低 ACE2 和/或 NEP 的水平，并增加胎盘 Ang II 水平（血管收缩素），可能导致胎盘 RAS 的血管收缩和舒张臂之间的不平衡。最终，胎盘 RAS 的这种失调可能导致胎盘灌注减少，这在 FGR 中是明显的。
