Starr Lisa M, Scott Marilyn E, Koski Kristine G
Institute of Parasitology, and.
School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Canada
J Nutr. 2015 Jan;145(1):41-50. doi: 10.3945/jn.114.202630. Epub 2014 Oct 29.
Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored.
Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth.
Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex.
Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af-monocyte chemotactic protein 1, af-interferon-γ, and af-eotaxin; and 3) liver and lung with f-leptin and af-corticosterone (all P ≤ 0.02).
PD and nematode infection impaired fetal mass and linear growth, respectively. Fetal mass, length, and individual organ masses were regulated by different hormones, growth factors, and cytokines.
蛋白质缺乏（PD）和肠道线虫感染在孕期常同时出现，并损害胎儿生长，但尚未探究其中复杂的信号网络。
我们的目的是评估受母体蛋白质缺乏和线虫感染影响且与胎儿生长相关的应激激素、生长因子和细胞因子。
采用2×2析因设计，给CD-1小鼠喂食蛋白质充足（PS；24%）或蛋白质缺乏（PD；6%）的等能量饮食，从妊娠第5天（GD5）开始，每5天对小鼠进行一次感染或不感染巴氏赫勒线虫处理。在妊娠第18天，使用Luminex检测母体血清（m）、胎儿血清（f）和羊水（af）中的生物标志物浓度。
母体蛋白质缺乏降低了胎儿体重（PS/未感染组1.25±0.02 g，PS/感染组1.19±0.02 g，vs. PD/未感染组1.11±0.02 g，PD/感染组0.97±0.02 g；P = 0.02）、胎儿肺（P = 0.005）和肝脏（P = 0.003）重量，但未影响脑重量；而母体感染降低了胎儿长度（PS/未感染组2.28±0.02 cm，PD/未感染组2.27±0.03 cm，vs. PS/感染组2.21±0.03 cm，PD/感染组2.11±0.02 cm；P = 0.05）和肾脏重量（P = 0.04）。蛋白质缺乏使所有样本中的应激激素（m-促肾上腺皮质激素、f-皮质酮、af-皮质酮）升高，并降低胰岛素样生长因子1（P≤0.01），但这些与胎儿体重或长度无关。胎儿体重与f-瘦素呈正相关（R² = 0.71，P = 0.0001），与胎儿细胞因子呈负相关[肿瘤坏死因子-α：R² = 0.62, P = 0.001；白细胞介素-4（IL-4）：R² = 0.63, P = 0.0004]。相反，母体感染降低了f-催乳素（P = 0.02），其与胎儿长度呈正相关（R² = 0.43；P = 0.03）；感染未影响其他生物标志物。回归分析显示器官生长、细胞因子和生长因子之间存在关联：1）胸腺、脾脏、心脏和脑与m-IL-10相关；2）脑和肾与f-血管内皮生长因子、af-单核细胞趋化蛋白1、af-干扰素-γ和af-嗜酸性粒细胞趋化因子相关；3）肝脏和肺与f-瘦素和af-皮质酮相关（均P≤0.02）。
蛋白质缺乏和线虫感染分别损害胎儿体重和线性生长。胎儿体重、长度和各器官重量受不同激素、生长因子和细胞因子调节。
