Impact of chorionic somatomammotropin RNA interference on uterine blood flow and placental glucose uptake in the absence of intrauterine growth restriction.
Impact of chorionic somatomammotropin RNA interference on uterine blood flow and placental glucose uptake in the absence of intrauterine growth restriction.
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在没有宫内生长受限的情况下，绒毛膜生长激素 RNA 干扰对子宫血流和胎盘葡萄糖摄取的影响。
DOI：
10.1152/ajpregu.00223.2020
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Anthony,RussellV
中科院分区：
文献类型：
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作者：
Tanner,AmeliaR;Lynch,CameronS;Ali,Asghar;Winger,QuintonA;Rozance,PaulJ;Anthony,RussellV
绒毛膜生长催乳素（CSH）是胎盘分泌最丰富的激素之一，但其确切功能仍不清楚。在近足月[胎龄135天（dGA）]，CSH RNA干扰（RNAi）导致两种不同的表型：1）宫内生长受限（IUGR）妊娠和2）胎儿和胎盘重量正常的妊娠。在这里，我们报告了没有IUGR的CSH RNAi妊娠的生理变化。在转移到同步化受体母羊中之前，用表达乱序对照（对照RNAi）或CSH特异性shRNA（CSH RNAi）的慢病毒构建体感染孵化囊胚（9 dGA）的滋养外胚层。在126 dGA时，对照RNAi（n= 6）和CSH RNAi（n= 6）妊娠装配有母体和胎儿导管。在132 dGA下测量子宫和脐带血流量，并通过Fick原理计算营养摄取。通过方差分析比较对照RNAi和CSH RNAi妊娠，并将显著性设定为P ≤ 0.05。在CSH RNAi妊娠中，绝对（mL/min）和相对（mL/min/kg胎儿）子宫血流量减少（P≤ 0.05），但脐带血流量不受影响。子宫动脉-静脉葡萄糖梯度（mmol/L）显著增加（P≤ 0.05）。子宫胎盘葡萄糖摄取（μmoL/min/kg胎盘）增加（P≤ 0.05），而脐带葡萄糖摄取（μmoL/min/kg胎儿）减少。我们的研究结果表明，即使在没有IUGR的情况下，CSH RNAi也具有显着的生理后果，并且比较表现出IUGR和非IUGR表型的CSH RNAi妊娠可能有助于确定CSH的直接影响及其对胎儿发育的潜在影响。
Chorionic somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term [135 days of gestational age (dGA)], CSH RNA interference (RNAi) results in two distinct phenotypes:1) pregnancies with intrauterine growth restriction (IUGR), and2) pregnancies with normal fetal and placental weights. Here, we report the physiological changes in CSH RNAi pregnancies without IUGR. The trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (Control RNAi) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 126 dGA, Control RNAi (n= 6) and CSH RNAi (n= 6) pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured at 132 dGA and nutrient uptakes were calculated by the Fick’s principle. Control RNAi and CSH RNAi pregnancies were compared by analysis of variance, and significance was set atP≤ 0.05. Absolute (mL/min) and relative (mL/min/kg fetus) uterine blood flows were reduced (P≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/L) was significantly (P≤ 0.05) increased. The uteroplacental glucose uptake (μmoL/min/kg placenta) was increased (P≤ 0.05), whereas umbilical glucose uptake (μmoL/min/kg fetus) was reduced. Our results demonstrate that CSH RNAi has significant physiological ramifications, even in the absence of IUGR, and comparing CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal development.