Chorionic somatomammotropin RNA interference alters fetal liver glucose utilization.
Chorionic somatomammotropin RNA interference alters fetal liver glucose utilization.
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DOI：
10.1530/joe-20-0375
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Anthony RV
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文献类型：
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作者：
Ali A;Swanepoel CM;Winger QA;Rozance PJ;Anthony RV
绒毛膜生长抑素(CSH)是一种胎盘特异性激素，与人和羊的胎儿生长、胎儿和母体代谢有关。我们推测CSH缺乏可能会影响绵羊胎肝葡萄糖的利用。为了获得CSH缺陷的妊娠，用表达CSH特异性shRNA(RNAi)或扰乱对照shRNA(SC)的慢病毒颗粒感染第9天孵化的囊胚，并将其转移到同步受体。CSH RNAi在胎龄135天(DGA)时产生两种不同的表型：胎儿宫内发育迟缓(RNAi-IUGR)或胎儿体重正常(RNAi-NW)。与SC相比，只有RNAi-IUGR妊娠的胎儿体重、胎儿肝脏和胎盘重量减轻(P<；0.05)。两种RNAi表型的脐动脉血浆胰岛素和胰岛素样生长因子1(IGF1)浓度降低，而胎肝胰岛素受体β(IRβ)浓度升高(P<0.05)。两种RNAi表型的胎肝中IGF1、IGF2、IGFBP2和IGFBP3的mRNA浓度均降低(P<0.05)。在两种RNAi表型中，胎肝糖原浓度和糖原合成酶1(GYS1)浓度升高(P<；0.05)，而胎肝磷酸化Gys(非活性Gys)浓度降低(P<；0.05)。仅在RNAi-IUGR胎肝中乳酸脱氢酶B(LDHB)浓度升高(P<0.05)，IGF2浓度降低(P<；0.05)。我们的发现表明，胎儿肝脏葡萄糖的利用受到CSH RNAi的影响，与IUGR无关，并且可能与两种RNAi表型的胎儿肝脏胰岛素敏感性增强有关。确定这两种表型的生理分支有助于区分CSH缺乏的直接影响或通过IUGR的间接影响。
Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We hypothesized that CSH deficiency could impact sheep fetal liver glucose utilization. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 days of gestational age (dGA); pregnancies with IUGR (RNAi-IUGR) or with normal fetal weight (RNAi-NW). Fetal body, fetal liver and placental weights were reduced (P<0.05) only in RNAi-IUGR pregnancies compared to SC. Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased, whereas insulin receptor beta (IRβ) concentration in fetal liver was increased (P<0.05) in both RNAi phenotypes. The mRNA concentrations of IGF1, IGF2, IGF binding protein 2 (IGFBP2) and IGFBP3 were decreased (P<0.05) in fetal livers from both RNAi phenotypes. Fetal liver glycogen concentration and glycogen synthase 1 (GYS1) concentration was increased (P<0.05), whereas fetal liver phosphorylated-GYS (inactive GYS) concentration was reduced (P<0.05) in both RNAi phenotypes. Lactate dehydrogenase B (LDHB) concentration was increased (P<0.05) and IGF2 concentration was decreased (P<0.05) in RNAi-IUGR fetal livers only. Our findings suggest that fetal liver glucose utilization is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced fetal liver insulin sensitivity in both RNAi phenotypes. Determining the physiological ramifications of both phenotypes, may help to differentiate direct effect of CSH deficiency or its indirect effect through IUGR.