OXYGEN AND PRENATAL GROWTH

氧气与产前生长

• 批准号: 3321277
• 负责人: JAMES METCALFE
• 金额: $ 8.87万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3321277
• 关键词: cell cycle; cell growth regulation; centrifugation; embryo /fetus hypoxia; gestational age; insulin; insulinlike factor; mass spectrometry; nonmammalian vertebrate embryology; oxygen consumption; oxygen tension; pregnancy circulation; prenatal growth disorder; radioimmunoassay; respiratory enzyme; respiratory gas transport; scintillation counter; statistics /biometry; thyroid hormones; tissue /cell culture

When fertile hen's eggs are switched from a 21% oxygen to a 60% oxygen environment on the fifteenth day of incubation, embryonic growth and 02 consumption are greater for the next three days than controls maintained at 21% 02. The opposite effects occur when the 02 concentration in the incubator is switched from 21% to 15% on the 15th day; embryonic growth slows and embryonic 02 consumption falls. These data suggest that oxygen availability normally limits the growth of the chick embryo beginning on the 15th day of incubation. We propose to investigate the mechanism by which 02 influences embryonic growth and metabolism. We will explore the possibility that 02 modifies growth through its action on the production of known anabolic hormones by measuring plasma concentrations of thyroid hormones, insulin, avian growth hormone, and avian insulin-like growth factors in circulating blood, taking samples from embryos in 15%, 21% and 60% 02. We will also add plasma from each of these experimental groups to chick embryo fibroblasts in culture and measure the rates of cell division, protein synthesis, and DNA synthesis. We will evaluate the possibility that 02 acts directly at the cellular level by comparing the biochemical characteristics of chick embryo tissues from 15% 02, 21% 02 and 60% 02 embryos with data obtained on cultured cells grown in media with different oxygen tensions. We will also attempt to develop the fetus of the guinea pig as a mammalian model of hyperoxic growth stimulation. We will increase 02 availability to the guines pig fetus beginning on day 53 of pregnancy by increasing maternal blood 02 capacity or decreasing maternal blood 02 affinity, or by a combination of these two procedures, measuring the effects by comparing fetal weight and the wet and dry weights of selected fetal organs with those from controls that have been cross-transfused without altering blood 02 affinity or capacity. Measurements of placental blood flow in experimental and control animals will be made at 63 days so the effects of changing blood respiratory characteristics on the blood flow to maternal organs, including placentas, can be evaluated. If 02 availability (the product of arterial 02 content and placental blood flow) is not increased by these changes in maternal blood, we will increase the hematocrit of one fetus, comparing its growth with controls. If one of these interventions evokes fetal growth acceleration, we will begin to compare 02-induced growth acceleration in the guinea pig with 02-induced growth acceleration of the chick embryo.

当可育母鸡的鸡蛋从21%的氧气切换到60%的氧气时 孵化第15天的环境、胚胎生长和02 在接下来的三天内的消耗量比维持在 21%02。相反的效果发生在02浓度在 孵化器在第15天从21%切换到15%；胚胎生长 消费放缓，处于萌芽状态的02消费量下降。这些数据表明氧气 可获得性通常会限制小鸡胚胎的生长 孵化第15天。我们建议通过以下方式来研究这一机制 哪种02会影响胚胎的生长和代谢。我们将探索 02通过其对生产的作用改变增长的可能性 通过测量甲状腺血浆浓度来了解已知的合成代谢激素 激素、胰岛素、禽类生长激素和禽类胰岛素样生长 循环血液中的因素，从胚胎中提取样本的比例分别为15%、21%和 60%02。我们还将把每个试验组的血浆添加到 培养鸡胚成纤维细胞，并测定细胞分裂率， 蛋白质合成和DNA合成。我们将评估这一可能性 02直接在细胞水平上起作用，通过比较生化 15%02、21%02和60%02鸡胚组织的特性 胚胎在培养细胞上获得的数据在不同的培养液中生长 氧气紧张。 我们还将尝试将豚鼠的胚胎发育成哺乳动物 高氧刺激生长模型。我们将把02的可用性提高到 豚鼠从妊娠第53天开始通过增加 母血02容量或降低母血02亲和力，或 这两个程序的组合，通过比较来衡量效果 胎儿体重和选定胎儿器官的湿重和干重 来自对照的那些在没有改变血液的情况下进行了交叉输血 02亲和力或能力。胎盘血流量的测定 实验动物和对照动物将在63天内制成，因此 血液呼吸特性变化对母体血流量的影响 器官，包括胎盘，可以进行评估。如果02可用( 动脉血氧分压和胎盘血流量的乘积)没有增加 通过母体血液的这些变化，我们将增加一个人的红细胞压积 胎儿，将其生长情况与对照组进行比较。如果其中一项干预措施 唤起胎儿生长加速，我们将开始比较02诱导 02促生长对豚鼠的促生长作用 小鸡胚胎的。