Poorly controlled diabetes mellitus alters placental structure, efficiency, and plasticity
Poorly controlled diabetes mellitus alters placental structure, efficiency, and plasticity
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DOI：
10.1136/bmjdrc-2020-001243
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发表时间：
2020-01-01
影响因子：
4.1
通讯作者：
Soares, Michael J.
中科院分区：
文献类型：
--
作者：
Nteeba, Jackson;Varberg, Kaela M.;Soares, Michael J.
血绒膜胎盘在母胎界面提供了一个重要的屏障，以调节母体的免疫耐受，并使母亲和孕体之间的气体和营养交换。妊娠结局受到糖尿病的不利影响，然而，控制不良的糖尿病对胎盘形成的影响，随后胎儿发育，是不完全understood.Research设计和方法链脲佐菌素被用来诱导妊娠大鼠高血糖症的目的，调查控制不良的糖尿病对胎盘形成和胎儿发育的影响。妊娠大鼠缺氧暴露的实验范式也被用来评估胎盘可塑性的属性。从妊娠第6.5天（gd）开始，将血糖正常和高血糖大鼠暴露于环境条件（类似于21%氧气）或缺氧（10.5%氧气），并在gd 13.5处死。为了确定是否高血糖和缺氧的相互作用直接改变滋养层细胞系的发展，大鼠滋养层干细胞（TS）培养在高葡萄糖（25 mM）和/或暴露于低氧（0.5%至1.5%）。结果糖尿病引起胎盘肥大和胎盘畸形，降低胎盘效率和胎儿大小。高浓度葡萄糖破坏大鼠TS细胞的体外分化。在体内也观察到滋养层分化改变的证据，因为高血糖影响结合区转录组并干扰子宫内滋养层侵袭和子宫螺旋动脉重塑。当暴露于缺氧时，高血糖大鼠在gd 9.5表现出增殖和外胎盘锥发育下降，并在gd 13.5完全丧失妊娠。此外，升高的葡萄糖浓度抑制TS细胞对缺氧的反应在vitro.Conclusions总体而言，这些结果表明，胎盘发育，效率和可塑性的改变可能有助于从妊娠并发糖尿病控制不良的后代的次优胎儿结局。
Introduction The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by diabetes mellitus; however, the effects of poorly controlled diabetes on placental formation, and subsequently fetal development, are not fully understood.Research design and methods Streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of poorly controlled diabetes on placental formation and fetal development. The experimental paradigm of hypoxia exposure in the pregnant rat was also used to assess properties of placental plasticity. Euglycemic and hyperglycemic rats were exposed to ambient conditions (similar to 21% oxygen) or hypoxia (10.5% oxygen) beginning on gestation day (gd) 6.5 and sacrificed on gd 13.5. To determine whether the interaction of hyperglycemia and hypoxia was directly altering trophoblast lineage development, rat trophoblast stem (TS) cells were cultured in high glucose (25 mM) and/or exposed to low oxygen (0.5% to 1.5%).Results Diabetes caused placentomegaly and placental malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat TS cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, hyperglycemic rats showed decreased proliferation and ectoplacental cone development on gd 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro.Conclusions Overall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by poorly controlled diabetes.