Chorionic Somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term (135 dGA), CSH RNA interference (RNAi) results in two distinct phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) 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 principle. Control RNAi and CSH RNAi pregnancies were compared by analysis of variance, and significance was set at P ≤ 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.

中文翻译：

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在没有宫内生长受限的情况下，绒毛膜促生长激素 RNA 对子宫血流和胎盘葡萄糖摄取的影响

绒毛膜促生长激素 (CSH) 是产生最丰富的胎盘激素之一，但其确切功能仍然难以捉摸。近期 (135 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。在转移到同步受体母羊之前，孵化囊胚 (9 dGA) 的滋养外胚层被表达乱序对照（对照 RNAi）或 CSH 特异性 shRNA（CSH RNAi）的慢病毒构建体感染。在 126 dGA 时，对照 RNAi (n = 6) 和 CSH RNAi (n = 6) 妊娠均配有母体和胎儿导管。在 132 dGA 时测量子宫和脐血流量，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，显着性设定为 P ≤ 0.05。CSH RNAi 妊娠的绝对（ml/min）和相对（ml/min/kg 胎儿）子宫血流量减少（P ≤ 0.05），但脐血流量未受影响。子宫动脉-静脉葡萄糖梯度（mmol/l）显着（P≤0.05）增加。子宫胎盘葡萄糖摄取量（μmol/min/kg胎盘）增加（P≤0.05），而脐带葡萄糖摄取量（μmol/min/kg胎儿）减少。我们的结果表明，即使在没有 IUGR 的情况下，CSH RNAi 也具有显着的生理学影响，