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Gender Specificity of Programmed Plasma Hypertonicity and Hemoconcentration in Adult Offspring of Water-Restricted Rat Dams

Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California Los Angeles, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center; Department of Pathology, Harbor-University of California Los Angeles Medical Center, Torrance, California mdesai{at}obgyn.humc.edu

Dave Gayle, PhD

Nathash Kallichanda, MD

Michael G. Ross, MD,MPH

Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California Los Angeles, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center; Department of Pathology, Harbor-University of California Los Angeles Medical Center, Torrance, California

Objective: We studied the impact of maternal water-restriction during rat pregnancy on newborn plasma composition, and determined the persistence of plasma composition alterations in adult offspring.

Methods: Maternal dams were water-restricted from 10 days of pregnancy until term (21 days) and throughout lactation to increase plasma sodium levels by 6 mEq/L. At 21 days of age, offspring were weaned, and subsequently maintained on ad libitum food and water until 12 weeks of age. Daily water and food intake was monitored. Blood samples and organs were collected from 1-day- and 12-week-old offspring. Hematocrit, plasma osmolality, sodium, and arginine vasopressin (AVP) levels were analyzed. Because water-restriction led to concomitant reduction in mternal food intake (ie, dehydration anorexia), henceforth these dams and their offspring are referred to as "water-deprived/food-reduced" rats.

Results: Water-deprived/food-reduced dams had significantly increased plasma sodium levels, reduced food intake, and lower body weight gain during pregnancy and lactation as compared to control dams. One-day-old newborns of water-deprived/food-reduced dams weighed 17% less and had increased plasma sodium levels, osmolality, and hematocrit. At 12 weeks of age, males exhibited 11% and females 19% reduction in body weight from controls. Notably, male offspring of water-deprived/food-reduced dams showed significantly elevated plasma sodium levels, osmolality, and hematocrit. Additionally, males demonstrated reduced adrenal growth and decreased water intake. Conversely, the female offspring had similar plasma osmolality with decreased sodium levels, though a persistently elevated hematocrit. No differences were evident in plasma AVP levels.

Conclusions: Maternal water deprivation/food reduction is associated with increased newborn plasma osmolality and sodium levels and long-term physiologic changes in the offspring. The gender-specificity of programmed hypersmolality, though not hemoconcentration, implicates differing pathways/mechanisms for these phenotypic alterations. The contributions of pregnancy hypertonicity versus nutrient restriction in the mechanism for programmed offspring phenotype remain to be elucidated.

Key Words: Arginine vasopressin • osmoregulation • hypertension • maternal nutrient-reduction

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