Preconceptional Lipid-Based Nutrient Supplementation in 2 Low-Resource Countries Results in Distinctly Different IGF-1/mTOR Placental Responses.
Preconceptional Lipid-Based Nutrient Supplementation in 2 Low-Resource Countries Results in Distinctly Different IGF-1/mTOR Placental Responses.
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DOI：
10.1093/jn/nxaa354
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发表时间：
2021-03-11
期刊：
影响因子：
--
通讯作者：
Powell TL
中科院分区：
文献类型：
--
作者：
Castillo-Castrejon M;Yang IV;Davidson EJ;Borengasser SJ;Jambal P;Westcott J;Kemp JF;Garces A;Ali SA;Saleem S;Goldenberg RL;Figueroa L;Hambidge KM;Krebs NF;Powell TL
妇女第一孕前孕产妇营养试验（WF）证明，在资源匮乏的国家，孕前母体小剂量脂质营养补充（SQLNS）改善了宫内线性生长。胎儿生长依赖于营养物质的可用性，并受胰岛素样生长因子1 （IGF-1）通过胎盘转运能力的改变而调节，并由雷帕霉素（mTOR）通路的机制靶点介导。我们的目的是评估胎盘mTOR和IGF-1信号在两个低资源国家接受孕前SQLNS后发育迟缓率高的妇女胎儿生长中的作用。作为WF研究的一部分，我们研究了48名来自危地马拉和巴基斯坦的妇女，从孕前到分娩，她们接受过或没有接受过SQLNS。分娩时采集胎盘样本（对照组，n = 24； SQLNS, n = 24）。检测胎盘真核翻译起始因子结合蛋白-1 （4E-BP1）、核糖体蛋白S6 （rpS6）、amp活化蛋白激酶α (AMPKA)、IGF-1、胰岛素样生长因子受体（IGF-1R）和妊娠相关血浆蛋白(PAPP)-A的蛋白或mRNA表达，以及IGF1启动子的DNA甲基化。检测母体血清IGF-1、胰岛素样生长因子结合蛋白(IGFBP)-3、IGFBP-4、IGFBP-5、PAPP-A、PAPP-A2、锌含量。危地马拉（26.5±1.3）和巴基斯坦（19.8±0.7）孕妇孕前BMI的平均值±SEM差异有统计学意义（P < 0.001）。在巴基斯坦参与者中，SQLNS增加了胎盘rpS6(T37/46):rpS6比率（1.5倍），降低了AMPKA(T172):AMPKA比率。胎盘IGF1 mRNA表达与出生体长和出生体重z-score呈正相关。胎盘PAPP-A（30倍）和母体血清锌（1.2倍）随SQLNS升高。在危地马拉参与者中，SQLNS不影响胎盘mTOR信号。胎盘IGF-1R蛋白表达与出生长度和出生体重z分数呈正相关。SQLNS增加胎盘PAPP-A（40倍）和母体血清IGFBP-4（1.6倍）。在营养状况不佳的巴基斯坦孕妇中，孕前SQLNS激活胎盘mTOR和IGF-1信号，并与胎儿生长改善有关。相反，在危地马拉妇女中，SQLNS没有激活胎盘营养感应通路。在经历儿童发育迟缓的人群中，孕前SQLNS仅在母体营养不良的情况下才能改善胎盘功能和胎儿生长。该试验在clinicaltrials.gov注册为NCT01883193。
Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS. We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P < 0.001). In Pakistani participants, SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively correlated with birth length and birth weight z-scores. Placental PAPP-A (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R protein expression was positively associated with birth length and birth weight z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 (1.6-fold). In Pakistani pregnant women with poor nutritional status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS did not activate placental nutrient-sensing pathways. In populations experiencing childhood stunting, preconceptional SQLNS improves placental function and fetal growth only in the context of poor maternal nutrition. This trial was registered at clinicaltrials.gov as NCT01883193.
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影响因子：
3.1
作者：
Hambidge KM;Krebs NF;Westcott JE;Garces A;Goudar SS;Kodkany BS;Pasha O;Tshefu A;Bose CL;Figueroa L;Goldenberg RL;Derman RJ;Friedman JE;Frank DN;McClure EM;Stolka K;Das A;Koso-Thomas M;Sundberg S;Preconception Trial Group
通讯作者：
Preconception Trial Group
影响因子：
3.4
作者：
Arimond, Mary;Zeilani, Mamane;Dewey, Kathryn G.
通讯作者：
Dewey, Kathryn G.
影响因子：
168.9
作者：
Black, RE;Morris, SS;Bryce, J
通讯作者：
Bryce, J
影响因子：
4.2
作者：
Jobarteh, Modou Lamin;McArdle, Harry J.;Moore, Sophie E.
通讯作者：
Moore, Sophie E.
影响因子：
1.7
作者：
Dissanayake, Hasthi U.;Anderson, Lyndal;Gordon, Adrienne
通讯作者：
Gordon, Adrienne