Kwan Sze Ting Cecilia, King Julia H, Yan Jian, Jiang Xinyin, Wei Emily, Fomin Vladislav G, Roberson Mark S, Caudill Marie A
Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Department of Biomedical Sciences, Cornell University, Ithaca, NY, United States.
Placenta. 2017 May;53:57-65. doi: 10.1016/j.placenta.2017.03.019. Epub 2017 Mar 30.
Normal placental vascular development is influenced by inflammatory, angiogenic and apoptotic processes, which may be modulated by choline through its role in membrane biosynthesis, cellular signaling and gene expression regulation. The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy.
Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses.
The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript (P ≤ 0.05) and protein (P ≤ 0.06) expression of TNF-a and IL-1β in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 (P = 0.045) and E18.5 (P = 0.067) but increased Il1b at E15.5 (P = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 (P = 0.034; 4X versus 2X) and E18.5 (P = 0.026; 4X versus 1X). MCS decreased (P = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger (P ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation.
MCS during murine pregnancy has fetal sex-specific effects on placental inflammation and angiogenesis, with possible consequences on placental vascular development.
正常的胎盘血管发育受炎症、血管生成和凋亡过程的影响，胆碱通过其在膜生物合成、细胞信号传导和基因表达调控中的作用，可能对这些过程进行调节。本研究探讨了孕期母鼠补充胆碱（MCS）对胎盘炎症、血管生成和凋亡过程的影响。
将怀孕的母鼠随机分为三组，分别给予正常啮齿动物饮食中胆碱含量的1倍、2倍或4倍，在胚胎第10.5天、12.5天、15.5天或18.5天采集组织，进行基因表达、蛋白质丰度和免疫组织化学分析。
胆碱诱导的炎症和血管生成标志物变化与胎儿性别有关。具体而言，在胚胎第10.5天和18.5天，4倍胆碱（相对于1倍胆碱）分别降低了雄性胎盘肿瘤坏死因子-α（TNF-a）和白细胞介素-1β（IL-1β）的转录本表达（P≤0.05）和蛋白质表达（P≤0.06）。在雌性胎盘中，4倍胆碱（相对于1倍胆碱）以双相模式调节白细胞介素-1β（Il1b）的转录本表达，在胚胎第12.5天（P=0.045）和18.5天（P=0.067）Il1b表达降低，但在胚胎第15.5天（P=0.031）Il1b表达增加。MCS还诱导雌性胎盘在胚胎第15.5天（P=0.034；4倍胆碱相对于2倍胆碱）和18.5天（P=0.026；4倍胆碱相对于1倍胆碱）血管内皮生长因子（Vegfa）表达上调。在胚胎第10.5天，MCS降低了胎盘凋亡（P=0.011；4倍胆碱相对于1倍胆碱）。此外，在整个妊娠期，额外补充胆碱后，母体螺旋动脉的管腔面积更大（P≤0.05；4倍胆碱相对于1倍胆碱）。
孕期母鼠补充胆碱对胎盘炎症和血管生成具有胎儿性别特异性影响，可能对胎盘血管发育产生影响。
