Taki Atsuko, Abe Mayumi, Komaki Motohiro, Oku Kikuko, Iseki Sachiko, Mizutani Shuki, Morita Ikuo
Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Congenit Anom (Kyoto). 2012 Jun;52(2):97-103. doi: 10.1111/j.1741-4520.2012.00359.x.
We hypothesized that gene expression in placenta and umbilical vessels are affected by intrauterine environment and some of the expression in umbilical vessels originating from the fetus could reflect fetal condition of these complicated pregnancies. Expression of angiogenesis-related factors and inflammatory cytokines were examined in placenta and umbilical vessels to clarify the effects of intrauterine environment of pregnancies complicated by preeclampsia and chorioamnionitis/funisitis. Forty-six preterm cesarean section deliveries were classified into three groups based on maternal condition during prenatal monitoring: preeclampsia (PE) (n = 11), chorioamnionitis/funisitis (CAM) (n = 8), and preterm control (PC) (n = 27). Angiogenesis-related factors and inflammatory cytokines in placentas, umbilical arteries and umbilical veins were analyzed by RT-PCR and immunohistochemistry. We demonstrated that Ang-2, Tie-2, and Dll4 increase in the placentas of PE compared to PC for the first time, and we confirmed the findings of previous reports showing the high expression of HIF-1α, sFlt-1, endoglin, leptin, and AT1R. Expression of angiogenesis-related factors, including HIF-1α, VEGF, angiopoietin, and TGF-β systems, and inflammatory cytokines, such as TNF-α and IL-6, increased in umbilical vessels of PE. Umbilical veins of CAM showed a higher Dll4 level than did PC. In preeclampsia, abnormal expressions of angiogenesis-related factors related to lifestyle diseases in adulthood were seen in the placenta and umbilical vessels as compared to PC. Chorioamnionitis/funisitis showed only upregulation of DII4 in umbilical veins.
我们假设胎盘和脐血管中的基因表达受宫内环境影响,并且源自胎儿的脐血管中的一些表达可以反映这些复杂妊娠的胎儿状况。检测胎盘和脐血管中血管生成相关因子和炎性细胞因子的表达,以阐明子痫前期及绒毛膜羊膜炎/脐带炎合并妊娠的宫内环境影响。46例早产剖宫产分娩根据产前监测时的母亲状况分为三组:子痫前期(PE)(n = 11)、绒毛膜羊膜炎/脐带炎(CAM)(n = 8)和早产对照组(PC)(n = 27)。通过逆转录聚合酶链反应(RT-PCR)和免疫组织化学分析胎盘、脐动脉和脐静脉中的血管生成相关因子和炎性细胞因子。我们首次证明,与PC组相比,PE组胎盘中血管生成素-2(Ang-2)、酪氨酸激酶受体2(Tie-2)和三角洲样蛋白4(Dll4)增加,并且我们证实了先前报告中显示缺氧诱导因子-1α(HIF-1α)、可溶性血管内皮生长因子受体-1(sFlt-1)、内皮糖蛋白、瘦素和血管紧张素Ⅱ1型受体(AT1R)高表达的结果。PE组脐血管中包括HIF-1α、血管内皮生长因子(VEGF)、血管生成素和转化生长因子-β(TGF-β)系统在内的血管生成相关因子以及炎性细胞因子如肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达增加。CAM组的脐静脉中Dll4水平高于PC组。与PC组相比,子痫前期患者胎盘和脐血管中出现与成年期生活方式疾病相关的血管生成相关因子异常表达。绒毛膜羊膜炎/脐带炎仅表现为脐静脉中DII4上调。