Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, 204 Craft Ave, Pittsburgh, PA 15213, United States.
Placenta. 2011 Dec;32(12):1004-9. doi: 10.1016/j.placenta.2011.09.010. Epub 2011 Oct 8.
Exposure of cultured trophoblasts to hypoxia is commonly used to interrogate the molecular mechanisms underlying placental hypoxic injury. We examined the effect of levels, durations, and patterns of hypoxia on gene expression patterns in primary human trophoblasts.
We exposed primary term human trophoblasts to either standard culture conditions (O(2) = 20%) or to static or alternating levels of oxygen (O(2) = 8%, or O(2) = 0%) either early or late in culture, and analyzed the expression of 34 genes that are known to be regulated in placentas from pregnancies complicated by fetal growth restriction (FGR).
Using multidimensional scale analysis, Euclidean distance, and hierarchical clustering, we found that gene expression patterns in cells exposed to O(2) = 8% were similar to patterns observed in O(2) = 20%, but more distant from patterns in O(2) = 0%. Alternating atmospheric oxygen (8% vs. 0%) yielded intermediate results. Changes in oxygen levels over a longer period had a greater effect on gene expression than short-term changes. Gene expression patterns in cultured trophoblasts did not fully capture expression patterns observed in biopsies from FGR placentas vs. control.
The level, duration, and patterns of hypoxia are critical in determining trophoblast gene expression, and therefore germane for analysis of trophoblast hypoxic injury.
将培养的滋养细胞暴露于低氧环境中常用于研究胎盘缺氧损伤的分子机制。我们研究了低氧水平、持续时间和模式对原代人滋养细胞基因表达模式的影响。
我们将原代足月人滋养细胞暴露于标准培养条件（氧分压 20%）或早期或晚期的静态或交替氧水平（氧分压 8%或氧分压 0%）下，并分析了已知在胎儿生长受限（FGR）妊娠胎盘中有调节作用的 34 个基因的表达。
使用多维尺度分析、欧几里得距离和层次聚类，我们发现暴露于氧分压 8%的细胞的基因表达模式与氧分压 20%下观察到的模式相似，但与氧分压 0%下的模式更为不同。大气氧的交替（8%对 0%）产生了中间结果。较长时间内氧水平的变化对基因表达的影响大于短期变化。培养的滋养细胞中的基因表达模式并不能完全捕捉到 FGR 胎盘活检中的表达模式。
低氧的水平、持续时间和模式是决定滋养细胞基因表达的关键因素，因此与分析滋养细胞缺氧损伤有关。
