(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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK063994-04
Application #
7048695
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2003-05-15
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$132,328
Indirect Cost
Name
La Biomed Research Institute/ Harbor UCLA Medical Center
Department
Type
DUNS #
069926962
City
Torrance
State
CA
Country
United States
Zip Code
90502
Keen-Rhinehart, Erin; Desai, Mina; Ross, Michael G (2009) Central insulin sensitivity in male and female juvenile rats. Horm Behav 56:275-80
Desai, Mina; Gayle, Dave A; Casillas, Ederlen et al. (2009) Early undernutrition attenuates the inflammatory response in adult rat offspring. J Matern Fetal Neonatal Med 22:571-5
Magee, Thomas R; Han, Guang; Cherian, Bindu et al. (2008) Down-regulation of transcription factor peroxisome proliferator-activated receptor in programmed hepatic lipid dysregulation and inflammation in intrauterine growth-restricted offspring. Am J Obstet Gynecol 199:271.e1-5
Desai, Mina; Guang Han; Ferelli, Monica et al. (2008) Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring. Reprod Sci 15:785-96
Desai, Mina; Gayle, Dave; Han, Guang et al. (2007) Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted offspring. Reprod Sci 14:329-37
Desai, Mina; Gayle, Dave; Babu, Jooby et al. (2007) The timing of nutrient restriction during rat pregnancy/lactation alters metabolic syndrome phenotype. Am J Obstet Gynecol 196:555.e1-7
Desai, Mina; Babu, Jooby; Ross, Michael G (2007) Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition. Am J Physiol Regul Integr Comp Physiol 293:R2306-14
Mansano, Roy; Desai, Mina; Garg, Ambica et al. (2007) Enhanced nephrogenesis in offspring of water-restricted rat dams. Am J Obstet Gynecol 196:480.e1-6
Choi, Gyu Yeon; Tosh, Darran N; Garg, Ambica et al. (2007) Gender-specific programmed hepatic lipid dysregulation in intrauterine growth-restricted offspring. Am J Obstet Gynecol 196:477.e1-7
Beloosesky, R; Gayle, D A; Amidi, F et al. (2006) Ontogenic expression of putative feeding peptides in the rat fetal brain and placenta. Nutr Neurosci 9:33-40

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