ZINC DEPRIVATION AND TERATOGENESIS

次优膳食缺锌是潜在的致病危险因素 用于妊娠并发症和新生儿发育。我们的实验室有 关注膳食缺锌对妊娠恒河猴的影响 了解导致“营养风险”的机制 怀孕了。我们的数据表明，缺锌的影响最大 在生长和发展时期有特点的。在接下来的五年里 几年后，我们将继续使用恒河猴来定义机制 这很容易导致“营养不良”的怀孕。特别是，我们 将研究中度缺锌对青春期恒河猴的作用 猴子。青少年恒河猴是人类最好的模型之一 青春期。我们将通过以下方式调查膳食缺锌的影响 关注缺锌对生长和营养的影响程度 通过对生长因子和其他荷尔蒙的影响来实现性成熟。更多 重要的是，利用怀孕的动物，母亲和受孕动物都会 进行研究以确定相关的基本生化和细胞损伤 缺锌。我们假设青春期女性的健康 会被同时存在的膳食缺锌和 将涉及释放、分布、结合或/或组织中的缺陷 对增长因素的反应。我们还假设同时存在 免疫和行为功能会出现异常。 此外，我们认为胎儿和胎儿可能会出现锌缺乏。 由于急性期反应扰乱了母体锌 动态平衡。我们认为，急性期反应，如 通过给药重组TNFpha，将导致所谓的 “母体毒性综合征”，并将包括锌的隔离 由于急性期蛋白产生增加而导致的母体肝脏 金属硫蛋白与锌在肝脏的摄取增加有关 血浆α2巨球蛋白的增加。这一切的后果 事件会减少锌向胚胎/胎儿的转移。这个 发生异常的原因有很多，包括锌 缺乏导致细胞脂质的速度和程度的变化， 核酸和蛋白质的氧化和DNA甲基化的改变。支持 因为这些假设将对锌和锌的健康产生重大影响 母体毒性/急性期反应期间的补充以及 为理解势能提供了统一的假设 多种外源性胁迫、缺锌与衰老的相互作用 发育异常。

Suboptimal dietary zinc deficiency is a potential etiological risk factor for pregnancy complications and neonatal development. Our laboratory has focused on the role of dietary zinc deficiency in pregnant rhesus monkeys to understand the mechanisms that lead to a "nutritionally-at-risk" pregnancy. Our data indicate that the effects of zinc deprivation are most marked during periods of growth and development. During the next five years we will continue our use of the rhesus monkey to define mechanisms that predispose to a "nutritionally-at-risk" pregnancy. In particular, we will study the role of moderate zinc deprivation in adolescent rhesus monkeys. Adolescent rhesus monkeys are amongst the best models for human adolescence. We will investigate the effects of dietary zinc deficiency by focusing on the extent to which zinc deficiency influences growth and sexual maturation via effects on growth factors and other hormones. More importantly, utilizing pregnant animals, both the mother and conceptus will be studied to identify basic biochemical and cellular lesions associated with zinc deficiency. We postulate that the health of adolescent females will be significantly disrupted by concurrent dietary zinc deficiency and will involve defects in the release, distribution, binding, or/or tissue response to growth factors. We also postulate that concurrent abnormalities will be seen in immunological and behavioral function. Additionally, we believe that embryonic and fetal zinc deficiency can arise as a consequence of acute phase reactions which disrupt maternal zinc homeostasis. We propose that acute phase reactions, such as that mediated by administration of recombinant TNFalpha, will lead to the so-called "maternal toxicity syndrome" and will include a sequestering of zinc in maternal liver due to enhanced production of the acute phase protein metallothionein coupled with an enhanced uptake of zinc into liver due to an increase in plasma alpha2 macroglobulin. The consequence of these events will be reduced zinc transfer to the embryo/fetus. The abnormalities that occur are due to a number of factors including zinc deficiency induced alterations in the rate and extent of cellular lipid, nucleic acid and protein oxidation and altered methylation of DNA. Support for these hypotheses would have major health implications, both for zinc supplementation during maternal toxicity/acute phase reactions as well as for providing a unifying hypothesis for understanding the potential interactions between multiple exogenous insults, zinc deficiency and developmental abnormalities.