title: Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.
abstract: Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible.
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan. Electronic address: akitake@ri.ncvc.go.jp.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Akitake
authors.affiliation: Department of Perinatology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Katsuragi
authors.affiliation: Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Hosokawa
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Obstetrics and Gynecology, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan.
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan. Electronic address: hosoda.hiroshi.ri@ncvc.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D000831:Animals, Newborn; D031204:Caloric Restriction / Q000009:adverse effects; D005317:Fetal Growth Retardation / Q000209:etiology / Q000473:pathology; D039382:Maternal Nutritional Physiological Phenomena; D009420:Nervous System / Q000196:embryology / Q000503:physiopathology
keywords: IUGR; Low birth weight; Maternal nutrition; Mice; Neurodevelopmental disorder; Sex difference