Late gestation fetal hyperglucagonaemia impairs placental function and results in diminished fetal protein accretion and decreased fetal growth.
Late gestation fetal hyperglucagonaemia impairs placental function and results in diminished fetal protein accretion and decreased fetal growth.
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DOI：
10.1113/jp281288
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
Rozance PJ
中科院分区：
文献类型：
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作者：
Cilvik SN;Wesolowski SR;Anthony RV;Brown LD;Rozance PJ
在胎盘功能不全和胎儿应激的情况下，胎儿胰高血糖素浓度升高。产后研究已经证明胰高血糖素在氨基酸代谢中的重要性，有限的胎儿研究表明胰高血糖素抑制脐带对某些氨基酸的摄取。我们假设慢性胎儿高胰高血糖素血症会减少胎儿的氨基酸转移并增加胎儿的氨基酸氧化。妊娠晚期单胎羊胎接受直接静脉输注胰高血糖素（GCG；5 或 50ng/kg/min；分别为 n=7 和 5）或载体对照（n=10）8-10 天。测量胎儿和母体营养浓度、子宫和脐血流量、胎儿亮氨酸通量、营养吸收率、胎盘绒毛膜生长激素（CSH）分泌以及胎盘目标基因表达。与对照组相比，GCG 胎儿的胎儿体重降低了 13%（p=0.0239），21 种氨基酸中 16 种的浓度降低了 28% 以上（p<0.02）。此外，GCG 胎儿的蛋白质合成降低了 49% (p=0.0005)，蛋白质积累降低了 92% (p=0.0006)。怀有 GCG 胎儿的母羊的子宫血流量降低了 33% (p=0.0154)，而脐血流量相似。胎儿高胰高血糖素血症使子宫对 10 种氨基酸的摄取量降低 >48% (p<0.05)，使脐带对 7 种氨基酸的摄取量降低 >29% (p<0.04)。与对照组相比，胎盘向母体循环中分泌的 CSH 减少了 80% (p=0.0080)。这项研究证明胰高血糖素对胎儿蛋白质积累和生长有负面影响。它还表明，胰高血糖素（一种胎儿来源的激素）对母体胎盘营养转运功能、胎盘 CSH 产生和子宫血流产生负调节。
Fetal glucagon concentrations are elevated in the setting of placental insufficiency and fetal stress. Postnatal studies have demonstrated the importance of glucagon in amino acid metabolism, and limited fetal studies have suggested that glucagon inhibits umbilical uptake of certain amino acids. We hypothesized that chronic fetal hyperglucagonemia would decrease amino acid transfer and increase amino acid oxidation by the fetus. Late gestation singleton fetal sheep received a direct intravenous infusion of glucagon (GCG; 5 or 50ng/kg/min; n=7 and 5, respectively) or a vehicle control (n=10) for 8–10 days. Fetal and maternal nutrient concentrations, uterine and umbilical blood flows, fetal leucine flux, nutrient uptake rates, placental secretion of chorionic somatomammotropin (CSH), and targeted placental gene expression were measured. GCG fetuses had 13% lower fetal weight compared to controls (p=0.0239) and >28% lower concentrations of 16 out of 21 amino acids (p<0.02). Additionally, protein synthesis was 49% lower (p=0.0005), and protein accretion was 92% lower in GCG fetuses (p=0.0006). Uterine blood flow was 33% lower in ewes with GCG fetuses (p=0.0154), while umbilical blood flow was similar. Fetal hyperglucagonemia lowered uterine uptake of 10 amino acids by >48% (p<0.05) and umbilical uptake of 7 amino acids by >29% (p<0.04). Placental secretion of CSH into maternal circulation was reduced by 80% compared to controls (p=0.0080). This study demonstrates a negative effect of glucagon on fetal protein accretion and growth. It also demonstrates that glucagon, a hormone of fetal origin, negatively regulates maternal placental nutrient transport function, placental CSH production, and uterine blood flow.