Centro de Investigaciones Médicas y Departamento de Nefrología, Escuela de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Reprod Biol Endocrinol. 2013 Jan 22;11:5. doi: 10.1186/1477-7827-11-5.
In humans, trophoblast invasion, vascular remodeling and placental development are critical to determine the fate of pregnancy. Since guinea-pigs (GP) and humans share common pregnancy features including extensive trophoblast invasion, transformation of the uterine spiral arteries and a haemomonochorial placenta, the GP animal model was deemed suitable to extend our knowledge on the spatio-temporal immunoreactive expression of the vasodilator arpeptide of the renin-angiotensin system, angiotensin-(1-7) [Ang-(1-7)] and its main generating enzyme, angiotensin converting enzyme 2 (ACE2).
Utero-placental units were collected in days 15, 20, 40 and 60 of a 64-67 day long pregnancy in 25 Pirbright GP. Ang-(1-7) and ACE2 expression in utero-placental units were evaluated by immunohistochemistry.
Ang-(1-7) and ACE2 were detected in the endothelium and syncytiotrophoblast of the labyrinthine placenta, interlobium, subplacenta, giant cells, syncytial sprouts, syncytial streamers, and myometrium throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts in spiral and mesometrial arteries expressed both factors. Immunoreactive Ang-(1-7) and ACE2 were present in decidua and in the vascular smooth muscle of spiral, myometrial and mesometrial arteries, which also express kallikrein (Kal), the bradykinin receptor 2 (B2R), vascular endothelial growth factor (VEGF) and its type 2 receptor (KDR), but no endothelial nitric oxide synthase (eNOS). In addition, the signal of Ang-(1-7) and ACE2 was especially remarkable in giant cells, which also show Kal, B2R. eNOS, VEGF and KDR.
The spatio-temporal expression of Ang-(1-7) and ACE2 in GP, similar to that of humans, supports a relevant evolutionary conserved function of Ang-(1-7) and ACE2 in decidualization, trophoblast invasion, vascular remodeling and placental flow regulation, as well as the validity of the GP model to understand the local adaptations of pregnancy. It also integrates Ang-(1-7) to the utero-placental vasodilatory network. However, its antiangiogenic effect may counterbalance the proangiogenic activity of some of the other vasodilator components.
在人类中，滋养细胞浸润、血管重塑和胎盘发育对于确定妊娠结局至关重要。由于豚鼠（GP）和人类具有共同的妊娠特征，包括广泛的滋养细胞浸润、子宫螺旋动脉的转化以及单绒毛膜胎盘，因此 GP 动物模型被认为适合扩展我们对肾素-血管紧张素系统血管舒张肽、血管紧张素（1-7）[Ang-（1-7）]及其主要生成酶血管紧张素转换酶 2（ACE2）在时空上免疫反应性表达的认识。
在 25 只 Pirbright GP 中，在 64-67 天长的妊娠第 15、20、40 和 60 天收集子宫胎盘单位。通过免疫组织化学评估子宫胎盘单位中 Ang-（1-7）和 ACE2 的表达。
在妊娠期间，Ang-（1-7）和 ACE2 在迷路胎盘、小叶间、胎盘下、巨细胞、合胞体芽、合胞体流和子宫肌层的血管内皮细胞和合体滋养层中被检测到。在妊娠晚期，螺旋和肠系膜动脉的血管周围或血管内滋养细胞表达这两种因子。免疫反应性 Ang-（1-7）和 ACE2 存在于蜕膜和螺旋、子宫肌和肠系膜动脉的血管平滑肌中，这些血管也表达激肽释放酶（Kal）、缓激肽受体 2（B2R）、血管内皮生长因子（VEGF）及其 2 型受体（KDR），但没有内皮型一氧化氮合酶（eNOS）。此外，Ang-（1-7）和 ACE2 的信号在巨细胞中特别明显，巨细胞也显示出 Kal、B2R、eNOS、VEGF 和 KDR。
GP 中 Ang-（1-7）和 ACE2 的时空表达与人类相似，支持 Ang-（1-7）和 ACE2 在蜕膜化、滋养细胞浸润、血管重塑和胎盘血流调节中的相关进化保守功能，以及 GP 模型理解妊娠局部适应的有效性。它还将 Ang-（1-7）整合到子宫胎盘血管舒张网络中。然而，其抗血管生成作用可能会抵消一些其他血管舒张成分的促血管生成活性。
