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Ketotic dairy cows have diminished fertility, and elevated levels of the ketone body beta-hydroxybutyrate (BHB) have been associated with poor embryonic development. We used an in vitro model based on either in vitro fertilization (IVF) or parthenogenesis to investigate the effects of BHB on the preimplantation bovine embryo development, epigenome, and transcriptome. Embryo culture medium was supplemented with BHB at a similar concentration to that present in the blood of cows suffering with severe ketosis, followed by analysis of blastocysts formation rate, diameter, total number of cells, levels of H3K9 beta-hydroxybutyrylation (H3K9bhb), apoptosis, and transcriptional alterations. As a result, we observed that BHB reduced the blastocysts rates, the diameter and the total number of cells in both parthenotes and IVF embryos. Exposure to BHB for either 3 or 7\u00a0days greatly increased the H3K9bhb levels in parthenotes at the 8-cells and blastocyst stages, and affected the expression of HDAC1, TET1, DNMT1, KDM6B, NANOG, and MTHFD2 genes. Additionally, culture of IVF embryos with BHB for 7\u00a0days dramatically increased H3K9bhb and reduced NANOG in blastocysts. RNA-seq analysis of IVF blastocysts revealed that BHB modulated the expression of 118 genes, which were involved with biological processes such as embryonic development, implantation, reproduction, proliferation, and metabolism. These findings provided valuable insights into the mechanisms through which BHB disrupts preimplantation embryonic development and affects the fertility in dairy cows.<\/jats:p>","DOI":"10.1093\/biolre\/ioae175","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T15:22:36Z","timestamp":1732548156000},"page":"253-272","source":"Crossref","is-referenced-by-count":6,"title":["Beta-hydroxybutyrate alters bovine preimplantation embryo development through transcriptional and epigenetic mechanisms"],"prefix":"10.1093","volume":"112","author":[{"given":"Juliano Rodrigues","family":"Sangalli","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"University of Sao Paulo Pirassununga , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Perecin","family":"Nociti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"University of Sao Paulo Pirassununga , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"Centre de Recherche en Reproduction Animale (CRRA) , Faculty of Veterinary Medicine, , Quebec,","place":["Canada"]},{"name":"University of Montreal Saint-Hyacinthe , Faculty of Veterinary Medicine, , Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Roberto","family":"Chiaratti","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolution , Center of Biological and Health Sciences, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"Federal University of S\u00e3o Carlos , Center of Biological and Health Sciences, , S\u00e3o 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Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena Fabiana Reis","family":"de Almeida Saraiva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"University of Sao Paulo Pirassununga , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Perecin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]},{"name":"University of Sao Paulo Pirassununga , Faculty of Animal Sciences and Food Engineering, , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano Coelho","family":"da 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