title: Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural development and function in resulting mice.
abstract: Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lv
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Guoying
authors.initials: G
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Cui
authors.forename: Man
authors.initials: M
authors.lastname: Tong
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D001757:Blastomeres / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000502:physiology*; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D016678:Genome; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000378:metabolism; D027724:Reproductive Techniques, Assisted
chemical_list: D020543:Proteome; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases
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