Baboon placental heparin-binding epidermal growth factor-like growth factor.
Baboon placental heparin-binding epidermal growth factor-like growth factor.
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DOI：
10.1530/rep-19-0487
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发表时间：
2020-07
期刊：
影响因子：
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通讯作者：
Albrecht ED
中科院分区：
文献类型：
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作者：
Armant DR;Aberdeen GW;Kilburn BA;Pepe GJ;Albrecht ED
胎盘绒毛外滋养层重构子宫螺旋动脉对于促进胎盘血流和胎儿发育是重要的。肝素结合表皮生长因子样生长因子（HB-EGF）是EGF家族成员，在体外刺激绒毛外滋养细胞分化和侵袭能力。妊娠期子痫前期孕妇的滋养层细胞表达和母体HB-EGF水平降低，但尚不确定HB-EGF是否在可能导致胎盘功能不全的早期下调。已经建立了一个非人灵长类动物模型，其中子宫螺旋动脉的滋养层重塑通过将雌激素的上升从狒狒妊娠的第二个三个月转移到第一个三个月来抑制。在本研究中，我们用这个模型来确定是否胎盘HB-EGF是改变过早升高雌激素在狒狒妊娠早期。子宫螺旋动脉重塑和胎盘HB-EGF和其他EGF家族成员的表达进行了评估，在妊娠第60天的狒狒与雌二醇（E2）之间的第25天和第59天的妊娠（任期= 184天）。与未处理狒狒相比，E2处理狒狒中直径为26 - 50、51 - 100和> 100 µ m的血管的螺旋动脉重塑百分比分别低90%、84%和70%（P <0.01）。免疫细胞化学染色/图像分析定量的HB-EGF蛋白在E2处理的狒狒胎盘中比未处理的狒狒减少3倍（P <0.01），而双调蛋白（AREG）和EGF表达没有改变。因此，我们建议，HB-EGF调节雌激素敏感性重塑的子宫螺旋动脉绒毛外滋养层在狒狒怀孕早期。
Placental extravillous trophoblast remodeling of the uterine spiral arteries is important for promoting blood flow to the placenta and fetal development. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGF family member, stimulates differentiation and invasive capacity of extravillous trophoblasts in vitro. Trophoblast expression and maternal levels of HB-EGF are reduced at term in women with preeclampsia, but it is uncertain whether HB-EGF is downregulated earlier when it may contribute to placental insufficiency. A nonhuman primate model has been established in which trophoblast remodeling of the uterine spiral arteries is suppressed by shifting the rise in estrogen from the second to the first trimester of baboon pregnancy. In the present study, we used this model to determine if placental HB-EGF is altered by prematurely elevating estrogen early in baboon gestation. Uterine spiral artery remodeling and placental expression of HB-EGF and other EGF family members were assessed on day 60 of gestation in baboons treated with estradiol (E2) daily between days 25 and 59 of gestation (term = 184 days). The percentages of spiral artery remodeling were 90%, 84% and 70% lower (P<0.01), respectively, for vessels of 26–50, 51–100 and >100 µm diameter in E2-treated compared with untreated baboons. HB-EGF protein quantified by immunocytochemical staining/image analysis was decreased 3-fold (P<0.01) in the placenta of E2-treated versus untreated baboons, while amphiregulin (AREG) and EGF expression was unaltered. Therefore, we propose that HB-EGF modulates the estrogen-sensitive remodeling of the uterine spiral arteries by the extravillous trophoblast in early baboon pregnancy.