98 THE FETAL AND POSTNATAL EFFECTS OF PERICONCEPTIONAL HYPERGLYCEMIA USING A RABBIT MODEL

Abstract

The objective of this study was to analyse the effects of maternal hyperglycemia during the periconception period on fetal and postnatal development using a rabbit model. Diabetes was induced in adult New Zealand female does by a single intravenous alloxan injection (group D). Glycemia was maintained between 3 and 5 g L–1 with 2 daily subcutaneous insulin injections. Does from group D and contemporary controls (group C) were naturally mated 1 wk after induction of diabetes in group D animals, without superovulation, and embryos collected after sacrifice on Day 4 post-coitum. In Expt. 1, embryos from D (n = 11) and C (n = 13) groups were transferred respectively to the right and left horns of 3 female recipients, which were killed on Day 28. In Expt. 2, 17 D and 16 C females were mated naturally. 68 D and 98 C embryos were collected and transferred to 26 non-diabetic recipients (6–7 embryos per doe). 17 females were pregnant with no difference between C and D recipients. Fetal development was monitored by ultrasound. At birth, litters were equilibrated in number. 15 D and 7 C pups (from 4 D and 2 C litters) were killed at weaning (1 month of age). The remaining 13 D and 26 C pups (4 D and 7 C litters) were allocated to 1 of 2 feeding groups: control or obesogenic diet. The obesogenic diet was based on the control diet supplemented with animal fat (suet, 200%) and glucose (200%). Bodyweight, adiposity, and glucose metabolism were monitored until sacrifice at 5 months of age. Data were analysed by ANOVA using litter (fetuses), litter and sex (weaning), and litter and diet (5 months) as co-factors. Sex effects at 5 months were not analysed due to small numbers of animals. Fetal development was not different between D and C groups. Fetal, placental, and fetal organ weights did not differ at Day 28, except for brain weight, which was significantly lower in D fetuses (0.86 ± 0.1 v. 1.05 ± 0.08 g; P < 0.05). There was no difference in litter size at birth (3.3 ± 0.3 v. 3.6 ± 0.5 pups for D and C groups, respectively; P = 0.5), but birthweight was significantly increased in D offspring (211 ± 6 v. 194 ± 6 g; P < 0.05). There was no difference in weight after 14 days. At 1 month of age, adiposity, plasma insulin and leptin concentrations were not different between groups. In contrast, in male D offspring, fasting glycemia was significantly lower (1.7 ± 0.2 v. 2.1 ± 0.02 g L–1; P < 0.01), plasma insulin-like growth factor 1 was significantly increased (P < 0.05) and kidney/bodyweight ratio was significantly reduced (0.41 ± 0.03 v. 0.45 ± 0.04; P < 0.01). From 12 wk of age, bodyweight became significantly different between D and C groups and according to diet (P < 0.005), with D individuals being lighter than C individuals for each dietary group. Finally, fasting glycemia was significantly higher in the animals fed the obesogenic diet (1.35 ± 0.05 v. 1.19 ± 0.05 g L–1; P < 0.04), regardless of group. These data suggest that maternal hyperglycemia during the periconceptional period affects glucose metabolism and organ development in offspring with sexual dimorphism.