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Imprint Osmoregulation/Maternally-Dehydrated Offspring

印记渗透调节/母体脱水后代

基本信息

批准号：
7224173
负责人：
Mina Desai
金额：
$ 13.13万
依托单位：
LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-05-15 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7224173
关键词：
Acute Adult Adult Children Age-Months Amniotic Fluid Arginine Argipressin Blood Plasma Volume Blood Pressure Blood Volume Cell Nucleus Chronic Coronary heart disease Deglutition Dehydration Desire for food Discipline of Nursing Elderly Electrolytes Environment Exercise Exposure to Failure Female Fluid Balance Food Patterns Gene Expression Regulation Human Hypernatremia Hypertension Hypothalamic structure Kidney Laboratories Lactation Liquid substance Measures Messenger RNA Molecular Neonatal Newborn Infant Osmolalities Osmoregulation Output Pathway interactions Peripheral Physiological Adaptation Pituitary Gland Plasma Predisposition Pregnancy Protein Biochemistry Rattus Regulation Sheep Sodium Stimulus System Urine Vasopressins Water Water consumption Water-Electrolyte Imbalance Week antidiuresis argipressin receptor critical developmental period day fetal human study imprint in utero in vivo intergenerational osmoreceptor response

项目摘要

DESCRIPTION (provided by candidate): Pregnancy evokes marked physiologic adaptations in the composition and volume of fluid compartments. During human and rat pregnancy, maternal blood volume increases and plasma osmolality decreases. Failure to adequately "reset" maternal plasma osmolality or exposure to maternal plasma hypertonicity, as a result of hyperemesis, exercise or dehydration, results in increased fetal plasma osmolality, which stimulates fetal arginine vasopressin (AVP) secretion, causing reduced amniotic fluid (AF) volume. Conversely, induced maternal plasma hypotonicity reduces fetal plasma osmolality, increases fetal urine flow, reduces fetal swallowing and increases AF volume in sheep and humans. More importantly, chronic in utero plasma tonicity alterations imprint newborn rat and human osmoregulation and renal responses including AVP synthesis and secretion, and possibly blood pressure. The imprinting of osmoregulation may increase the susceptibility of the newborn and/or adult to water/electrolyte imbalance, hypertension and coronary heart disease. It is also possible that the imprinted osmoregulation may have intergenerational effects such that the female offspring may not appropriately reset their plasma osmolality and adequately expand their plasma volume during their subsequent pregnancies. Our preliminary studies of rats indicate that maternal dehydration during pregnancy results in hypernatremia and hypertonicity in the newborn. We hypothesize that maternal dehydration alters basal plasma tonicity in newborn and adult offspring, as a result of: (1) an elevated osmoregulatory set-point of the central osmoreceptor nuclei, and altered cellular volume regulation or (2) reduced basal AVP mRNA and synthesis, and AVP secretion in response to osmotic stimuli, and/or (3) reduced AVP-induced renal antidiuresis. We propose to examine central and peripheral mechanisms for the imprinting of the AVP-osmoregulatory system. We will determine the molecular and cellular mechanism(s) and peripheral renal AVP receptor changes. Finally, we will delineate the critical period during which imprinting of the AVP/osmoregulatory pathway occurs.

描述（由候选人提供）：怀孕会引起体液室的成分和体积的显着生理适应。在人类和大鼠怀孕期间，母体血容量增加，血浆渗透压降低。由于剧吐、运动或脱水，未能充分“重置”母体血浆渗透压或暴露于母体血浆高渗状态，会导致胎儿血浆渗透压升高，从而刺激胎儿精氨酸加压素（AVP）分泌，导致羊水（AF）量减少。相反，引起的母体血浆低渗会降低胎儿血浆渗透压，增加胎儿尿流量，减少胎儿吞咽并增加绵羊和人类的 AF 体积。更重要的是，慢性子宫内血浆张力改变会影响新生大鼠和人类的渗透压调节和肾脏反应，包括 AVP 合成和分泌，以及可能的血压。渗透压调节的印记可能会增加新生儿和/或成人对水/电解质失衡、高血压和冠心病的易感性。印迹渗透压调节也可能具有代际效应，使得雌性后代在随后的怀孕期间可能无法适当地重置其血浆渗透压并充分扩大其血浆容量。我们对大鼠的初步研究表明，母亲在怀孕期间脱水会导致新生儿出现高钠血症和肌张力过高。我们假设母体脱水会改变新生儿和成年后代的基础血浆张力，其原因是：（1）中央渗透压感受器核的渗透调节设定点升高，细胞体积调节改变或（2）基础AVP mRNA和合成减少，以及响应渗透压刺激的AVP分泌减少，和/或（3）AVP诱导的减少肾脏抗利尿作用。我们建议检查 AVP 渗透调节系统印记的中枢和外周机制。我们将确定分子和细胞机制以及外周肾 AVP 受体的变化。最后，我们将描述 AVP/渗透调节途径印记发生的关键时期。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Down-regulation of transcription factor peroxisome proliferator-activated receptor in programmed hepatic lipid dysregulation and inflammation in intrauterine growth-restricted offspring.

DOI：
10.1016/j.ajog.2008.05.022
发表时间：
2008-09
期刊：
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
影响因子：
9.8
作者：
Magee, Thomas R.;Han, Guang;Cherian, Bindu;Khorram, Omid;Ross, Michael G.;Desai, Mina
通讯作者：
Desai, Mina

Central insulin sensitivity in male and female juvenile rats.