Altered health outcomes in adult offspring of Sprague Dawley and Wistar rats undernourished during early or late pregnancy.
BACKGROUND
Birth weight in humans has been inversely associated with adult disease risk. Results of animal studies have varied depending on species, strain, and treatment.


METHODS
We compared birth weight and adult health in offspring following 50% maternal undernutrition on gestation days (GD) 1-15 (UN1-15) or GD 10-21 (UN10-21) in Sprague Dawley and Wistar rats. Offspring from food-deprived dams were weighed and cross-fostered to control dams. Litters were weighed during lactation and initiating at weaning males were fed either control or a high-fat diet. Young and mature adult offspring were evaluated for obesity, blood pressure (BP), insulin response to oral glucose, and serum lipids. Nephron endowment, renal glucocorticoid receptor, and renin-aldosterone-angiotensin system components were measured.


RESULTS
The UN10-21 groups had birth weights lower than controls and transient catch up growth by weaning. Neither strain demonstrated obesity or dyslipidemia following prenatal undernutrition, but long-term body weight deficits occurred in the UN groups of both strains. High-fat diet fed offspring gained more weight than control offspring without an effect of prenatal nutrition. Sprague Dawley were slightly more susceptible than Wistar rats to altered insulin response and increased BP following gestational undernutrition. Nephron endowment in Sprague Dawley but not Wistar offspring was lower in the UN10-21 groups. Glucocorticoid and renin-aldosterone-angiotensin system pathways were not altered.


CONCLUSIONS
The most consistent effect of maternal undernutrition was elevated BP in offspring. Long-term health effects occurred with undernutrition during either window, but the UN10-21 period resulted in lower birth weight and more severe adult health effects.
Ellis-Hutchings
Robert G
RG
Toxicology Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA. Rellis-hutchings@dow.com
Zucker
Robert M
RM
Grey
Brian E
BE
Norwood
Joel
J
Richards
Judy H
JH
Lau
Christopher
C
Rogers
John M
JM
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001724:Birth Weight; D001835:Body Weight; D005260:Female; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D039401:Prenatal Nutritional Physiological Phenomena; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014886:Weaning
D007328:Insulin; D020738:Leptin; D008055:Lipids