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Am J Physiol Regul Integr Comp Physiol 297: R835-R843, 2009. First published July 15, 2009; doi:10.1152/ajpregu.00072.2009
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ARTICLES

Maternal obesity accelerates fetal pancreatic β-cell but not {alpha}-cell development in sheep: prenatal consequences

Stephen P. Ford,1,2 Liren Zhang,1,2 Meijun Zhu,1,2 Myrna M. Miller,1,2 Derek T. Smith,3 Bret W. Hess,1,2 Gary E. Moss,1,2 Peter W. Nathanielsz,1,4 and Mark J. Nijland1,4

1Center for the Study of Fetal Programming, 2Department of Animal Science, and 3Division of Kinesiology and Health, University of Wyoming, Laramie, Wyoming; and 4Center for Pregnancy and Newborn Research, University of Texas, Health Sciences Center, San Antonio, Texas

Submitted 3 February 2009 ; accepted in final form 29 June 2009

Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by ~43% and ~6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased β-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal β-cell maturation and may contribute to premature β-cell function loss and predisposition to obesity and metabolic disease in offspring.

sheep; fetal growth; pancreatic function


Address for reprint requests and other correspondence: M. J. Nijland, Center for Pregnancy and Newborn Research, The Univ. of Texas Health Science Center at San Antonio, Dept. OB/GYN, 7703 Floyd Curl Dr., MSC 7836, San Antonio, TX 78229 (e-mail: nijland{at}uthscsa.edu)






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