Responses of Bovine Early Embryos to S-adenosyl Methionine Supplementation in Culture

Abstract

Aim: There is a growing concern about the potential adverse effects of high dose folic acid (FA) supplementation before and during pregnancy. FA metabolism generates S-adenosyl methionine (SAM) which is an important cofactor of epigenetic programming. We sought to assess the impact of a large dose of SAM on early embryo development. Materials & methods:In vitro cultured bovine embryos were treated with SAM from the eight-cell stage to the blastocyst stage. In addition to the phenotype, the genome-wide epigenetic and transcription profiles were analyzed. Results: Treatment significantly improved embryo hatching and caused a shift in sex ratio in favor of males. SAM caused genome-wide hypermethylation mainly in exonic regions and in CpG islands. Although differentially expressed genes were associated with response to nutrients and developmental processes, no correspondence was found with the differentially methylated regions, suggesting that cellular responses to SAM treatment during early embryo development may not require DNA methylation-driven changes. Conclusion: Since bovine embryos were not indifferent to SAM, effects of large-dose FA supplements on early embryonic development in humans cannot be ruled out.

Keywords::

• bovine early embryo
• CpG enrichment
• DNA methylation
• epigenome
• S-adenosyl methionine
• SAM
• sex ratio
• transcriptome

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2016-0022

Author contributions

HAS Saadi, MA Sirard and C Robert designed the study. HAS Saadi performed the IVF, phenotypic, transcriptome (RT-qPCR) and epigenetics (DNA methylation and pyrosequencing) experiments as well as data acquisition and analysis. D Gagné performed the transcriptome microarray. E Fournier performed bioinformatics analyses. LMB Baldeon and HAS Saadi performed the mitochondrial staining. C Robert supervised the work. HAS Saadi and C Robert drafted the final manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors acknowledge I Gilbert for her kind assistance with pyrosequencing.

Financial & competing interests disclosure

HAS Saadi was supported by EmbryoGENE, REDIH, RQR-CREATE and NSERC PGD2 scholarships. Financial support for this work was received from the Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Network EmbryoGENE NETPG 340825-06. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

HAS Saadi was supported by EmbryoGENE, REDIH, RQR-CREATE and NSERC PGD2 scholarships. Financial support for this work was received from the Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Network EmbryoGENE NETPG 340825-06. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.