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Composition of Maternal Diet Influences Fetal Brain Gene Expression and Offspring Behavior in Mice

Key findings

  • How the composition of maternal diet during pregnancy affects fetal brain development has not been well studied
  • In wild-type mice, exposure to a maternal diet that was relatively deficient in micronutrients was associated with differential expression of more 1,600 fetal brain genes compared with exposure to a micronutrient-enriched diet
  • Neonates exposed to the micronutrient-deficient diet exhibited earlier achievement of strength and coordination-associated milestones but delayed sensory maturation compared with those exposed to the micronutrient-enriched diet
  • Behavioral differences between offspring exposed to the two maternal diet groups persisted into adult life
  • When examining the impact of maternal dietary or other environmental manipulations on fetal brain development and offspring behavior, it is important to select the appropriate control diet, matched by micro- and macronutrients

Maternal over- or undernutrition during pregnancy are known to harm fetal brain development and alter offspring behavior in animal models and in humans, but there is more to learn about exactly why. One possibility is that the harm is associated, at least in part, with diet composition, including relative micronutrient deficiency (proposed to co-exist frequently with maternal obesity) and macronutrient deficiency.

Andrea Edlow, MD, MSc, an investigator in the Vincent Center for Reproductive Biology at Massachusetts General Hospital, Diana Bianchi, MD, head of Prenatal Genomics & Therapy at the National Human Genome Research Institute, and colleagues investigated that question as part of a larger research program examining maternal nutrition in a mouse model of Down's syndrome. According to their report in Frontiers in Neuroscience, two maternal diets that differed primarily with respect to micronutrient composition had significantly different effects on fetal brain gene expression and offspring behavior.

Study Methods

Only wild-type fetuses and offspring were analyzed for this study.

At the time of breeding, each dam–sire pair started one of two commercially available chow diets:

  • Pelleted: Richer in isoflavones, macronutrients (except carbohydrate), amino acids and micronutrients (including all vitamins and most minerals) compared with the powdered chow
  • Powdered: Richer in carbohydrate and favorable polyunsaturated fatty acids than the pelleted chow, but deficient in micronutrients

The dams continued on the diet throughout pregnancy and lactation. Offspring were weaned to the same diet they were exposed to in utero and during lactation.

Pelleted and powdered chow did not differ with respect to their effect on dam weight gain during pregnancy or embryo weight/length at day 15.5 of gestation.

Brain Gene Expression

On embryonic day 15.5, some of the pregnant dams had RNA extracted from embryonic forebrains. 1,647 genes were found to be differentially expressed in the embryonic brains exposed to powdered chow versus those exposed to pelleted chow. The maternal diet accounted for 63% of the variation in fetal brain gene expression.

Offspring Weight Gain and Behavior

Maternal diet did not have a significant impact on neonatal weight trajectory. Neonates that had been exposed to the powdered-chow maternal diet achieved body righting, strength and coordination milestones significantly faster than the group exposed to pelleted chow. However, they were significantly delayed in sensory maturation (eye opening and the tactile, auditory and tonic labyrinthine reflexes).

When evaluated as adults, powdered chow-exposed offspring exhibited hyperactivity and hippocampal learning deficits compared with the group exposed to the more micronutrient-rich pelleted chow.

Research Implications

The differences between maternal diet groups in gene expression and behavior occurred in the absence of any differences in maternal, fetal or neonatal weight gain, suggesting that they were not attributable to overt nutrient excess or deficiency.

The findings highlight the critical importance of selecting the appropriate control diet, matched for macro- and micronutrients, when examining the impact of maternal dietary or other environmental manipulations on fetal brain development and offspring behavior.

Learn more about the Vincent Center for Reproductive Biology

Learn more about the Maternal-Fetal Medicine Program at Mass General

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