The effects of feed restriction during organogenesis on embryo-fetal development in the rat

• Published in: Birth defects research. Part B. Developmental and reproductive toxicology 2005-10, Vol.74 (5), p.442-449
• Main Authors: Fleeman, T.L., Cappon, G.D., Chapin, R.E., Hurtt, M.E.
• Format: Article
• Language: English
• Subjects: Animal Feed; Animals; Biological and medical sciences; Body Weight; Bone and Bones - embryology; Bone and Bones - physiology; developmental toxicity; Embryo, Mammalian; Embryology: invertebrates and vertebrates. Teratology; Embryonic Development; feed restriction; Female; Fetal Development; Fetal Weight; Food Deprivation; Fundamental and applied biological sciences. Psychology; Organ Size; Organogenesis; Pregnancy; rat; Rats; Rats, Sprague-Dawley; teratology; Teratology. Teratogens
• ISSN: 1542-9733; 1542-9741
• DOI: 10.1002/bdrb.20056

BACKGROUND: Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate safety data that may be challenging to interpret. To aid with this, the effects of feed restriction and subsequent body weight reductions on embryo‐fetal development were investigated in the rat. METHODS: Groups of 20 timed pregnant female Sprague‐Dawley rats were offered Certified Rodent Diet 5002 either ad libitum or in restricted amounts of 20, 15, 10, and 7.5 g/day from Gestation Day (GD) 6–17. Clinical signs, body weights, and food consumption were recorded. Cesarean sections were performed on GD 21 and fetuses were sexed, weighed, and examined for external, visceral, and skeletal development. RESULTS: Mean maternal body weights at the end of the feed restriction period, GD 18, were reduced 0.87 ×, 0.80 ×, 0.69 ×, and 0.63 × control mean in the 20, 15, 10, and 7.5g/day groups, respectively. Mean body weight gains for the restriction period inclusive, GD 6–18, were 0.49 × and 0.24 × control at 10 and 7.5 g/day, respectively, and a mean body weight loss occurred at 10 and 7.5 g/day (0.95 × and 0.85 × mean GD 6 body weight, respectively). Fetal body weights were reduced 0.95 ×, 0.93 ×, 0.90 ×, and 0.76 × control at 20, 15, 10, and 7.5 g/day, respectively. This resulted in a reduction in gravid uterine weight at 10 and 7.5 g/day. There were no external, visceral, or skeletal malformations attributed to feed restriction. There was an increase in the skeletal variation of wavy ribs and a decrease in ossification at 7.5 g/day. CONCLUSIONS: These data demonstrate that feed restriction‐induced reductions in maternal gestational body weight gain of ∼50% compared to ab lib fed rats only caused a reduction in fetal body weight. Even up to a 15% maternal gestational body weight loss had no effect on embryo viability in rats, but retarded fetal growth significantly enough to induce minor changes in skeletal development. There were no external, visceral, or skeletal malformations associated with any of the levels of maternal body weight reduction or loss. Birth Defects Res B 2005. © 2005 Wiley‐Liss, Inc.