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Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring
British Journal of Nutrition ( IF 3.6 ) Pub Date : 2020-01-21 , DOI: 10.1017/s000711452000015x
Jean-Baptiste Armengaud 1 , Zelie Dennebouy 1 , Danny Labes 2 , Catherine Fumey 3 , Anne Wilson 2, 3 , Fabio Candotti 4 , Catherine Yzydorczyk 1 , Umberto Simeoni 1
Affiliation  

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P < 0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P < 0·05). At PND180, the protein expression of the lymphotoxin β receptor (P < 0·05), the autoimmune regulator (P < 0·05) and Forkhead Box P3 (FoxP3; P < 0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P < 0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

中文翻译:

母体低蛋白饮食诱导的子宫内生长受限导致成年雄性大鼠后代胸腺结构和功能的长期改变

早期营养不良是子宫内生长受限的第一个环境原因,会损害胸腺的发育。在小鼠和绵羊模型中,在年轻时报告了胸腺结构和功能的改变。然而,关于成年期胎儿营养不良的胸腺后果的描述很少。本研究调查了与妊娠期对照饮食相比,暴露于母体低蛋白饮食 (mLPD) 的大鼠的雄性后代在出生后第 180 天 (PND180) 观察到的胸腺结构、蛋白质表达和细胞选择过程。暴露于 mLPD 的成年后代的胸腺指数较低(< 0·05)。暴露于 mLPD 的成年后代的胸腺皮质髓质比率较低(< 0·05)。在 PND180,淋巴毒素的蛋白质表达β受体(< 0·05), 自身免疫调节剂 (< 0·05) 和叉头盒 P3 (FoxP3;< 0·05) 在 mLPD 组中均显着降低。mLPD组CD4+:CD8+单阳性胸腺细胞亚群比例和CD4+:CD8+淋巴细胞亚群比例增加(< 0·05)。CD3+淋巴细胞中,CD4+CD8+双阳性淋巴细胞、CD31+近期胸腺细胞和CD4+FoxP3+淋巴细胞的比例在mLPD和对照组之间无显着差异。这些发现表明,妊娠期间的 mLPD 在成年雄性大鼠后代的胸腺结构发育和胸腺细胞成熟和选择过程中引起了长期的改变。
更新日期:2020-01-21
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