Abstract Developing embryos are susceptible to fluctuations in the nutrients and metabolites concentrations within the reproductive tract, which can lead to alterations in their developmental trajectory. 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 days 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 days 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.

Juliano Rodrigues Sangalli

Ricardo Perecin Nociti

Marcos Roberto Chiaratti

Alessandra Bridi

Ramon Cesar Botigelli

Dewison Ricardo Ambrizi

Helena Fabiana Reis de Almeida Saraiva

Felipe Perecin

Juliano Coelho da Silveira

Pablo Juan Ross

Flávio Vieira Meirelles

Biology of Reproduction

生殖生物学 (BOR) 是生殖研究学会的官方期刊，发表关于生殖生物学领域广泛主题的原创研究，以及对当前重要或争议主题的评论。 BOR 一直是发表生殖生物学领域原创研究的引用率最高的期刊之一。

Biology of Reproduction is the official journal of the Society for the Study of Reproduction, publishing original research on a wide range of topics in the field of reproductive biology, as well as commentary on current important or controversial issues. It has consistently been one of the most highly cited journals for original research in the field of reproductive biology.

《Biology of Reproduction》是生殖研究学会的官方期刊，发表关于生殖生物学领域的原创研究，涵盖广泛的主题，并对当前重要或有争议的议题进行评论。该期刊一直是生殖生物学领域中引用率最高的原创研究发表平台之一。

Category	Quartile
生物学	2
生物学, 生殖生物学	3

Beta-hydroxybutyrate alters bovine preimplantation embryo development through transcriptional and epigenetic mechanisms

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Journal Info

Category	Quartile
REPRODUCTIVE BIOLOGY	2