Maternal Diet Effects on Body Weight and Behavior Responses in Offspring.

Abstract

The Barker hypothesis envisages that intra-uterine effects of maternal diet during pregnancy can manifest themselves in the later life of her offspring, in some cases with predictable pathological consequences. Here, we have determined whether or not murine dams (NIH Swiss) that had been fed three nutritionally complete diets: 1) very high in fat (VHF), 2) low in fat (LF), 3) a control (C) diet intermediate in fat and calories (Purina 5015) continuously from 5 wks of age for up to 40 wks, produced pups whose behavior and body weight differed across groups. Freshly weaned female pups (n = 20/ group) were randomly selected from offspring of each dietary group of dams, housed 3-4 to a cage, and fed a standard mouse chow (Purina 5001). Mice were weighed at weaning (3wks), 4 to 6 and 14 to 16 wks of age, and their behavioral responses examined at these last two time-points (trials 1 and 2) by using an ActivityPro open-field maze, which tracks movement, periods at rest, exploratory behavior, total distance traveled, stereotypical behaviors, and speed by the frequency at which the mice break laser beams directed at various levels within the maze. Four mazes were run simultaneously, with one mouse per maze, and activity data accumulated for 15 min. All dependent variables, dam body weights, pup body weights, and pup behavior data were analyzed by ANOVA. While the average body weight at weaning was not different between the three groups, by 4 to 6 wks of age the daughters from the VHF dams (31.1 ± 0.8g) weighed more than those born to the LF and 5015 control dams (28.1 ± 0.8 and 28.0 ± 0.8g, respectively; P<0.01). These results were consistent at 14 to 16 wks (P<0.01), with daughters of VHF dams weighing 37.4 ± 1.4g compared to those born to the LF (30.0 ± 1.4) and 5015 control dams (32.0 ± 1.4). Additionally, offspring weight was correlated (r=0.5) with prior maternal body weight during pregnancy irrespective of diet. In behavioral trial 1, VHF offspring tended to spend more time in the center of the maze, suggesting they were less anxious than the LF offspring (P<0.06). Additionally, the daughters of the VHF dams spent more time traveling around the cage (P<0.05) and in engaging in stereotypical behaviors (P< 0.01), such as grooming and sniffing than daughters of LF dams. At behavioral trial 2, the daughters of VHF dams continued to engage in more stereotypic behavior than the LF offspring (P<0.01), but by this point, the VHF daughters spent more time resting than the LF offspring (P<0.01). In contrast, the LF daughters traveled further and faster than the offspring of VHF and 5015 dams (P<0.01). We then determined whether mouse weight was correlated with behavior in the maze. For trial 1, increased mouse weight strongly correlated in a positive manner with stereotypical behavior and decreased speed (P<0.01). At trial 2, increased body weight continued to be negatively correlated with speed (P<0.01), and there was an overall trend towards a reduction in distance traveled. In summary, maternal diet and body weight during pregnancy strongly influence subsequent body weight and behavioral parameters of daughters, and, in turn, offspring body weight was correlated with some aspects of their behavior. These outcomes might have important implications for human pregnancies. Supported by NIH grant HD 44042. (poster)