Cuffe J S M, Walton S L, Steane S E, Singh R R, Simmons D G, Moritz K M
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Placenta. 2014 Nov;35(11):953-61. doi: 10.1016/j.placenta.2014.09.004. Epub 2014 Sep 16.
The renin angiotensin system (RAS) is an important mediator of placental development. However, a comprehensive expression profile for 8 key components of the placental RAS throughout murine gestation has not been performed. Furthermore, maternal hypoxia induces dysregulation of RAS expression in fetal tissues but the effects on the murine placental RAS are less well known.
Placentas were collected from male and female CD1 mouse fetuses at seven gestational ages for qPCR analysis of Agt, Ren1, Atp6ap2, Ace, Ace2, Agtr1a, Agtr2 and Mas1. mRNA localisation of Agtr1 and Mas1 and protein localisation of ACE and ACE2 was determined at E18.5. To determine the effects of maternal hypoxia on the placental RAS, mice were housed in 12% oxygen from E14.5-E18.5 and placentas examined at E18.5.
All RAS genes were expressed in the placenta throughout pregnancy and expression varied with fetal sex and age. Agtr1 was expressed within the labyrinth while Mas1 was expressed within the intraplacental yolk sac. ACE and ACE2 were localised to both labyrinth and junctional zones. In response to maternal hypoxia the expression of Agt, Ace and Ace2 was decreased but expression of Agtr1a was increased. Ace and Agtr1a mRNA levels were affected to a greater extent in females compared to males.
Collectively, the location within the placenta as well as the expression profiles identified, support a role for the placental RAS in labyrinth development. The placental RAS is disturbed by maternal hypoxia in a sexually dimorphic manner and may contribute to impairment of placental vascular development.
肾素血管紧张素系统（RAS）是胎盘发育的重要调节因子。然而，尚未对整个小鼠妊娠期胎盘RAS的8个关键成分进行全面的表达谱分析。此外，母体缺氧会导致胎儿组织中RAS表达失调，但对小鼠胎盘RAS的影响尚不清楚。
在七个妊娠阶段从雄性和雌性CD1小鼠胎儿收集胎盘，用于对Agt、Ren1、Atp6ap2、Ace、Ace2、Agtr1a、Agtr2和Mas1进行qPCR分析。在胚胎第18.5天确定Agtr1和Mas1的mRNA定位以及ACE和ACE2的蛋白定位。为了确定母体缺氧对胎盘RAS的影响，将小鼠从胚胎第14.5天至18.5天饲养在含12%氧气的环境中，并在胚胎第18.5天检查胎盘。
所有RAS基因在整个孕期的胎盘中均有表达，且表达随胎儿性别和年龄而变化。Agtr1在迷路中表达，而Mas1在胎盘内卵黄囊中表达。ACE和ACE2定位于迷路和交界区。母体缺氧时，Agt、Ace和Ace2的表达降低，但Agtr1a的表达增加。与雄性相比，雌性的Ace和Agtr1a mRNA水平受影响更大。
总体而言，在胎盘中的定位以及所确定的表达谱均支持胎盘RAS在迷路发育中的作用。胎盘RAS受到母体缺氧的性别差异干扰，可能导致胎盘血管发育受损。
