Birth weight (BW) is an important indicator for newborn health. Both high and low BW is associated with increased risks for adult metabolic diseases. AMPK (Adenosine monophosphate (AMP)-activated protein kinase), mTOR (Mechanistic Target of Rapamycin), and Insulin/IGF1 (Insulin-like Growth Factor 1) pathways may function as placental sensors of maternal hormonal and nutritional status. However, the physiological role of these pathways in placenta has not been completely elucidated. To evaluate expression and activation of AMPK, mTOR, and insulin/IGF1 pathways, and its association with placental weight (PW), BW, and maternal hormonal and metabolic status, we performed a cross-sectional study in placentas from non-obese mothers with SGA (n=17), AGA (n=19) and LGA (n=10) newborns. We analyzed placental expression of total and phosphorylated key proteins from the AMPK, mTOR and Insulin/IGF1 pathways. Maternal and cord blood hormones were determined by ELISA. AMPK and LKB1 activation correlated negatively with PW and BW, cord leptin, and pregestational BMI. Placental SIRT1 inversely correlated with BW, cord leptin, neonatal HOMA-IR, and maternal IGF1. PGC1 correlated negatively with PW and BW. Phosphorylated mTOR positively correlated with maternal glucose, PW and BW. IGF1R was lower in SGA. No changes in pIGF1R, INSRb, total Akt or pAkt were found, pPDK1 was lower in SGA and LGA. These results suggest that placental AMPK, insulin/IGF1, and mTOR pathways may influence fetal growth, perhaps regulating placental physiology, even in metabolically healthy pregnancies. Our study highlights these nutrient sensing pathways as potential molecular mechanisms modulating placental adaptations and thus, long-term metabolic health.

中文翻译：

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胎盘营养感应通路与出生体重的关联

出生体重（BW）是新生儿健康的重要指标。高和低 BW 都与成人代谢疾病的风险增加有关。AMPK（一磷酸腺苷 (AMP) 激活的蛋白激酶）、mTOR（雷帕霉素的机制靶点）和胰岛素/IGF1（胰岛素样生长因子 1）通路可能充当母体激素和营养状况的胎盘传感器。然而，这些途径在胎盘中的生理作用尚未完全阐明。为了评估 AMPK、mTOR 和胰岛素/IGF1 通路的表达和激活，及其与胎盘重量 (PW)、BW 和母体激素和代谢状态的关联，我们对来自非肥胖母亲的胎盘进行了横断面研究SGA (n=17)、AGA (n=19) 和 LGA (n=10) 新生儿。我们分析了来自 AMPK、mTOR 和胰岛素/IGF1 通路的总和磷酸化关键蛋白的胎盘表达。通过ELISA测定母体和脐带血激素。AMPK 和 LKB1 激活与 PW 和 BW、脐带瘦素和孕前 BMI 呈负相关。胎盘 SIRT1 与 BW、脐带瘦素、新生儿 HOMA-IR 和母体 IGF1 呈负相关。PGC1α 与 PW 和 BW 呈负相关。磷酸化的 mTOR 与母体葡萄糖、PW 和 BW 呈正相关。SGA 中的 IGF1R 较低。未发现 pIGF1R、INSRb、总 Akt 或 pAkt 发生变化，SGA 和 LGA 中的 pPDK1 较低。这些结果表明胎盘 AMPK、胰岛素/IGF1 和 mTOR 通路可能影响胎儿生长，甚至可能在代谢健康的妊娠中调节胎盘生理。