© 1993 Oxford University Press
research-article |
Food Restriction during Organogenesis in Rabbits: Effects on Reproduction and the Offspring
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company Ann Arbor, Michigan 48105
Received October 5, 1992; accepted June 18, 1993
Food Restriction during Organogenesis in Rabbits: Effects on Reproduction and the Offspring. PETRERE, J. A., ROHN, W. R., GRANTHAM, L. E., II, AND ANDERSON, J. A. (1993). Fundam. Appl. Toxicol. 21, 517–522.
To assess the effects of markedly restricted food intake versus ad libitum feeding or a slightly restricted feeding regimen during the period of organogenesis we fed groups of 16–18 pregnant rabbits Purina Certified High Fiber Chow ad libitum, 150 g/day, 75 g/day, or 15 g/day on Gestation Days 6 to 18 inclusive. Prior to and after organogenesis the animals were provided food ad libitum (ad lib). Clinical observations, body weights, and food and water consumption were recorded daily. On Gestation Day 30 each doe was euthanatized and necropsied, and maternal and fetal data were collected. Each fetus was examined for external, visceral, and skeletal variations and malformations. Ossification parameters were also evaluated. Statistical analyses were conducted in two ways, first comparing the restricted groups to the ad lib group and second comparing the 15 and 75 g/day groups to the 150 g/day group. During Days 6–18, the 15 and 75 g/day groups had significantly decreased weight gain (actual weight loss), compared to the groups fed 150 g/day or ad lib. Water consumption was also significantly decreased in the 15 g/day group during this period, compared to the ad lib group. When food was provided ad lib on Days 19–30 to the restricted groups, weight gain was significantly higher in the 15 and 75 g/day groups than the group previously given 150 g/day and the ad lib group. There were no differences in water consumption during that period. Abortion occurred in three 15 g/day animals. Pregnancy rate and numbers of corpora lutea, implantation sites, live and dead fetuses and resorptions, pre- and postimplantation loss, and placental weights were similar among groups. Fetal sex ratio and survival at term were comparable between the ad lib group and the restricted groups. In the 15 g/day group, mean fetal weights were lower than those in the 150 g/day and the ad lib groups. None of the fetuses from food-restricted does had external or visceral malformations, whereas two littermates from the ad lib group had malformations of the heart or gallbladder. Except for a significant increase in the percentage of litters with external or visceral variations in the 15 g/day group compared to the 150 g/day group, there were no significant differences between groups in the incidences of variations or malformations. Our findings agree with those in the literature in that abortion is increased and fetal weights are reduced when maternal food intake is severely restricted during organogenesis. Contrary to a previous report also using 15 g/day during organogenesis [R. L. Clark, R. T. Robertson, C. P. Peter, J. A. Bland, T. E. Nolan, L. Oppenheimer, and D. L. Bokelman (1986). Fundam. Appl. Toxicol. 7, 292–286], we did not have an increased incidence of fetal malformations. This study indicates that the influence of reduced food intake and body weight loss during organogenesis is equivocal in the induction of teratogenicity in rabbits.