Mice Born to Mothers Fed a Diet High in Omega-6 Fatty Acids and Low in Omega-3 Fatty Acids During Pregnancy Exhibit Various Behavioral Changes Including Impaired Social Behaviors and Enhanced Recognition Memory

Background: Modern dietary trends have led to an increase in foods that are relatively high in n–6 PUFAs and low in n–3 PUFAs. We previously reported that the offspring of mother mice that consumed a diet high in n–6 linoleic acid (LA) and low in n–3 α-linolenic acid (ALA), hereinafter called the LA^high/ALA^low diet, exhibited behavioral abnormalities related to anxiety and feeding. Objectives: We currently lack a comprehensive overview of the behavioral abnormalities in these offspring, which was investigated in this study. Methods: C57BL/6J virgin female mice at 11 wk of age were fed either a control diet or the LA^high/ALA^low diet, mated at 13 wk of age, and maintained on their respective diet throughout gestation. At birth, the lactating mothers’ diet was replaced with standard laboratory feed pellets. After weaning, the offspring continued to receive standard laboratory feed pellets, and both male and female offspring at 1–63 wk of age were analyzed using a comprehensive behavioral test battery (n = 6–14 offspring/group and offspring in each group were derived from ≥3 independent litters). Results: Both male and female offspring exposed in utero to the LA^high/ALA^low diet exhibited impaired social behaviors, including the lower number of contacts with novel mice in the social interaction test [diet, F_(1,15) = 9.807, P = 0.007, 2-way analysis of variance (ANOVA)], and also showed enhanced recognition memory in the object location test (diet, F_(1,36) = 6.779, P = 0.013, 2-way ANOVA) compared with offspring exposed in utero to the control diet. In addition, compared with sex-matched controls, female offspring displayed hyperactivity in the open field test (F_(1,36) = 6.097, P = 0.018, simple main effect analysis). Conclusions: The maternal balance between dietary n–6 and n–3 PUFAs during pregnancy can have significant effects on the offspring's behaviors, lasting well into adulthood.