MON-019 Maternal Behaviour in Mice Is Modified by a High Fat Diet in Pregnancy

Abstract

Background: About a third of pregnant women of age 20-39 are obese, which carries significant risks for the mother and fetus, and adversely impacts pregnancy outcome. Specifically, women with obesity are at increased risk for peripartum depression. Maternal behaviour in mice is influenced by changes in hormone signaling in pregnancy, which is associated with effects on adult neurogenesis in the brain. Thus, we used mouse as a model system to gain further insight into the possible relationship between overeating/obesity and brain physiology and maternal behaviour. Objective: To assess the ability of a high-fat diet (HFD) versus a regular chow diet (CD), starting up to 10 weeks pre-pregnancy, to modify glucose clearance before and during pregnancy and affect maternal behaviour in the CD1 mouse. Study Design: Two groups of 3-4 week-old female CD1 mice were fed a HFD (fat=60 kcal%; carbohydrate=20 kcal%; protein=20 kcal%) or CD (fat=14 kcal%; carbohydrate=60 kcal%; protein=26 kcal%) and maintained on their respective diets throughout the study and weighed periodically. After at least 4 weeks of feeding on their diets, mice were allowed to breed. Glucose tolerance was tested using 2 g/kg of i.p. glucose at gestational day (GD) -1) after fasting (16 hours-overnight) as well as during pregnancy at GD16.5. An even number of pregnant and non-pregnant females were selected for each diet for maternal behaviour testing. Tests include an assessment of nest building at GD16.5-17 (use of nesting material and nest quality), and after birth pup retrieval at postpartum day (PD) 3, 4 and 5 (time of retrieval of each of the four pups within six minutes) using video capture. Results: The HFD led to a significant increase in weight relative to mice fed a CD. HFD impaired glucose-load clearances at GD -1 and 16.5 (p<0.05) compared to mice fed a CD. Mice fed on HFD performed poorly in the nest building task (p<0.01) as well as demonstrated a reduced completion rate on the pup retrieval test on PD3 (CD=8/10 vs. HFD 2/9 mice) but their retrieval response latency was improved by PD4 (CD=8/10 vs. HFD 8/9 mice) and PD5 (CD=7/10 vs. HFD 7/9 mice). Conclusions: Initial observations suggest that a HFD for at least 4 weeks before and during pregnancy results in overweight CD1 mice with impaired glucose clearance, and a negative effect on maternal behaviour as assessed by nest-building during pregnancy and pup retrieval postpartum; however, with regard to the latter, mice on the HFD show the ability to learn. Additional behavioural tests for locomotion, anxiety, risk avoidance and object recognition memory during or after pregnancy, as well as associated changes in hormonal signaling and adult neurogenesis are also currently under investigation.