title: Maternal n-3 polyunsaturated fatty acid deprivation during pregnancy and lactation affects neurogenesis and apoptosis in adult offspring: associated with DNA methylation of brain-derived neurotrophic factor transcripts.
abstract: In this study, we hypothesized that n-3 polyunsaturated fatty acid (PUFA) deficiency during pregnancy and lactation will make a lasting impact on brain neurogenesis and apoptosis of the adult offspring and that these harmful effects cannot be reversed by n-3 PUFA supplementation after weaning. Moreover, the underlying mechanisms may be attributable to the epigenetic changes of brain-derived neurotrophic factor (BDNF). C57BL/6J female mice were fed with n-3 PUFA-deficient diet (n-3 def) or n-3 PUFA-adequate diet (n-3 adq) throughout pregnancy and lactation. At postnatal 21 days, equal numbers of male pups from both groups were fed the opposite diet, and the remaining male pups were fed with the same diets as their mothers until 3 months of age. Feeding the n-3 adq diet to pups from the maternal n-3 def group significantly increased the n-3 PUFA concentration but did not change expressions of calretinin, Bcl2, and Bax in the hippocampus. Feeding the n-3 def diet to pups from the maternal n-3 adq group significantly reduced the n-3 PUFA concentration but did not reduce expressions of calretinin and Bcl2. Similarly, BDNF levels, especially mRNA expressions of BDNF transcripts IV and IX, were also reduced by maternal n-3 def and not reversed by n-3 PUFA supplementation after weaning. The decrease in BDNF expression by maternal n-3 def diet was associated with greater DNA methylation at special CpG sites. These results suggested that the maternal n-3 PUFA deficiency during pregnancy and lactation imprints long-term changes of brain development in adult offspring.
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Fan
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Huicong
authors.initials: H
authors.lastname: Fu
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Dong
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. Electronic address: qkm6@hotmail.com.
authors.forename: Kemin
authors.initials: K
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D064032:Calbindin 2 / Q000378:metabolism; D019175:DNA Methylation; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D044127:Epigenesis, Genetic; D015525:Fatty Acids, Omega-3 / Q000172:deficiency*; D005247:Feeding Behavior; D005260:Female; D047109:Fetal Development; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D064032:Calbindin 2; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein
keywords: Adult mice; Apoptosis; BDNF; DNA methylation; N-3 polyunsaturated fatty acids; Neurogenesis