Institute for Women's Healthcare (IFG), Erlangen, Germany; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Placenta. 2018 Feb;62:58-65. doi: 10.1016/j.placenta.2017.12.019. Epub 2017 Dec 30.
Preeclampsia is a hypertensive, gestational disease, which is still the leading cause of pregnancy related morbidity and mortality. The impairment of placental angiogenesis and vascularization is discussed to be of etiopathologic relevance. Deytrosination and tyrosination of α-tubulin is important for the stability and dynamics of microtubules. An increase of α-tubulin detyrosination leads to microtubule stabilization, which is an essential prerequisite for physiologic vascular tube morphogenesis during angiogenesis. So far, little is known about the specific localization of detyrosinated (detyr) and tyrosinated (tyr) tubulin in the placenta and its relevance for preeclampsia.
Placental expression of detyr- and tyr-tubulin was analyzed by immunohistochemistry, immunofluorescence and western blot. For western blot quantification we used biopsies from healthy placentas (n = 21) and placentas from pregnancies complicated with small for gestational age (n = 5), preeclampsia (n = 5) or both (n = 5).
Specific placental localization of detyr-tubulin was detected in the fetal endothelial cells of the placenta. Villous and extravillous trophoblasts as well as villous stroma cells were tyr-tubulin positive. Detyr-tubulin protein expression was significantly decreased in placentas complicated by preeclampsia.
In summary, we report an accumulation of detyr-tubulin in villous vessels of the placenta and a significantly reduced level of detyr-tubulin in placental biopsies of preeclampsia cases. The reduction of placental detyr-tubulin in preeclampsia could suggest a deficit in villous vascular plasticity and might be associated with the impaired arborization of the disease.
子痫前期是一种高血压的妊娠疾病,仍然是妊娠相关发病率和死亡率的主要原因。胎盘血管生成和血管化的损伤被认为与发病机制有关。α-微管蛋白的去酪氨酸化和酪氨酸化对微管的稳定性和动力学很重要。α-微管蛋白去酪氨酸化的增加导致微管的稳定,这是血管生成过程中生理性血管管腔形态发生的必要前提。到目前为止,关于去酪氨酸化(detyr)和酪氨酸化(tyr)微管蛋白在胎盘中的特异性定位及其与子痫前期的关系知之甚少。
通过免疫组织化学、免疫荧光和 Western blot 分析胎盘中 detyr-和 tyr-微管蛋白的表达。Western blot 定量分析使用来自健康胎盘(n=21)和因胎儿生长受限(n=5)、子痫前期(n=5)或两者(n=5)而复杂的胎盘的活检。
在胎盘的胎儿内皮细胞中检测到 detyr-微管蛋白的特异性胎盘定位。绒毛和绒毛外滋养层以及绒毛间质细胞均为 tyr-微管蛋白阳性。子痫前期复杂的胎盘中 detyr-微管蛋白的蛋白表达显著降低。
总之,我们报告了 detyr-微管蛋白在胎盘绒毛血管中的积累,以及子痫前期胎盘活检中 detyr-微管蛋白水平显著降低。子痫前期胎盘中 detyr-微管蛋白的减少可能表明绒毛血管可塑性不足,可能与疾病的分支受损有关。