Excess Folic Acid Supplementation before and during Pregnancy and Lactation Alters Behaviors and Brain Gene Expression in Female Mouse Offspring

Nutrients

Zhixing Lu¹  Yan Zhou¹  Yongqi Chen¹  Wenyan Sun¹  Fei Liu²  Hongyan Lin³  Feng Wu³  Xingyue Yang⁴  Xin Shen⁴  Li Huang⁴  Qian Wu⁴  Dandan Chu⁴ 

[1] Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China;Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA;Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China;Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China;

关键词: folic acid;    pregnancy;    lactation;    behaviors;    gene expression;    female;   

DOI  :  10.3390/nu14010066

来源: DOAJ

【 摘 要 】

Use of folic acid (FA) during early pregnancy protects against birth defects. However, excess FA has shown gender-specific neurodevelopmental toxicity. Previously, we fed the mice with 2.5 times the recommended amount of FA one week prior to mating and during the pregnancy and lactation periods, and detected the activated expression of Fos and related genes in the brains of weaning male offspring, as well as behavioral abnormalities in the adults. Here, we studied whether female offspring were affected by the same dosage of FA. An open field test, three-chamber social approach and social novelty test, an elevated plus-maze, rotarod test and the Morris water maze task were used to evaluate their behaviors. RNA sequencing was performed to identify differentially expressed genes in the brains. Quantitative real time-PCR (qRT-PCR) and Western blots were applied to verify the changes in gene expression. We found increased anxiety and impaired exploratory behavior, motor coordination and spatial memory in FA-exposed females. The brain transcriptome revealed 36 up-regulated and 79 down-regulated genes in their brains at weaning. The increase of Tlr1; Sult1a1; Tph2; Acacb; Etnppl; Angptl4 and Apold1, as well as a decrease of Ppara mRNA were confirmed by qRT-PCR. Among these genes; the mRNA levels of Etnppl; Angptl4andApold1 were increased in the both FA-exposed female and male brains. The elevation of Sult1a1 protein was confirmed by Western blots. Our data suggest that excess FA alteres brain gene expression and behaviors in female offspring, of which certain genes show apparent gender specificity.

【 授权许可】

Unknown