title: Natrium fluoride influences methylation modifications and induces apoptosis in mouse early embryos.
abstract: This study epigenetically examined the effect of fluoride on early embryos of Kunming mice administered with 0, 20 (low), 60 (medium), and 120 mg/L (high) sodium fluoride (NaF). The results showed that NaF repressed oocyte maturation, fertilization and blastocyst formation in all NaF-treated groups. Meanwhile, TUNEL assay showed that embryo apoptosis was induced dramatically in blastocyst stage at either low or medium doses, and in 8-cell stage at high dose, compared to the control, suggesting a dose-dependent effect. Furthermore, the immunostaining displayed global increases of DNA methylation, H3K9m2 and H3K4m2 with increasing dose, which were consistent with gene expression results, exhibiting general increases of DNMT1, DNMT3a, G9a, LSD1, and MLL1 and a reduction of JHDM2a in transcription and protein levels. More closely, the differential methylation domain in parentally imprinted gene H19 showed low methylation, while materanlly imprinted gene IGF2 showed high methylaiton in NaF-treated groups compared to the control group, which corresponded with high expression of H19 and low expression of IGF2 confirmed by qPCR. Collectively, we demonstrated that fluoride epigenetically impaired mouse oocyte maturation and embryonic development, supplying a better knowledge of fluoride in toxicology and a deeper evaluation of its potential influence in physiological and clinical implications.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi Province The People's Republic of China 712100.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Fu
authors.forename: Xinying
authors.initials: X
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D001757:Blastomeres / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D005260:Female; D005306:Fertilization / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D059471:In Vitro Oocyte Maturation Techniques; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics*; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology*
chemical_list: C094335:H19 long non-coding RNA; D006657:Histones; C513121:IGF2 protein, mouse; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D012969:Sodium Fluoride