Protein-restricted diet during pregnancy after insemination alters behavioral phenotypes of the progeny

Tamio Furuse,Kimio Kobayashi,Ikuko Yamada,Hideki Kaneda,Takae Hirasawa,Misho Kashimura,Takashi Kohda,Shigeharu Wakana,Kunio Miyake,Takeo Kubota,Tomoko Kushida,Fumitoshi Ishino

doi:10.1186/s12263-016-0550-2

Abstract

BackgroundEpidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models. However, previous experimental hyponutrition or protein-restricted (PR) diets affected stages other than the fetal stage, such as formation of the egg before insemination, milk composition during lactation, and maternal nursing behavior.ResultsWe conducted in vitro fertilization and embryo transfer in mice and allowed PR diet and folic acid-supplemented PR diet to affect only fetal environments. Comprehensive phenotyping of PR and control-diet progenies showed moderate differences in fear/anxiety-like, novelty-seeking, and prosocial behaviors, irrespective of folic-acid supplementation. Changes were also detected in gene expression and genomic methylation in the brain.ConclusionsThese results suggest that epigenetic factors in the embryo/fetus influence behavioral and epigenetic phenotypes of progenies. Significant epigenetic alterations in the brains of the progenies induced by the maternal-protein restriction were observed in the present study. To our knowledge, this is first study to evaluate the effect of maternal hyponutrition on behavioral phenotypes using reproductive technology.

Highlights

Epidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models
The three different diets used in this study were proteinrestricted (PR), folic acid-supplemented PR (FA), and the control diet (CD) (Table 1)
In vitro fertilized eggs were transferred to three different kinds of ICR recipient mothers that consumed the PR, FA, or control diet (CD) 1 month before the embryo transfer

Summary

Introduction

Epidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models. Previous experimental hyponutrition or protein-restricted (PR) diets affected stages other than the fetal stage, such as formation of the egg before insemination, milk composition during lactation, and maternal nursing behavior. Maternal PR diet, affects fetal environments and formation of the egg before insemination, nutritional condition of maternal milk, and maternal nursing behavior, and it has potential confounding variables at different stages. We performed in vitro fertilization (IVF) to produce neonates and obtained progenies that were adopted by foster mothers before weaning. This allowed the PR diet to affect only the fetal stage of development

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Discussion

Conclusion