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The effect of vitrification on blastocyst mitochondrial DNA dynamics and gene expression profiles

  • Embryo Biology
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Abstract

Purpose

Does vitrification/warming affect the mitochondrial DNA (mtDNA) content and the gene expression profile of blastocysts?

Methods

Prospective cohort study in which 89 blastocysts were obtained from 50 patients between July 2017 and August 2018. mtDNA was measured in a total of 71 aneuploid blastocysts by means of real-time polymerase chain reaction (RT-PCR). Transcriptomic analysis was performed by RNA sequencing (RNA-seq) in an additional 8 aneuploid blastocysts cultured for 0 h after warming, and 10 aneuploid blastocysts cultured for 4–5 h after warming.

Results

A significant decrease in mtDNA content just during the first hour after the warming process in blastocysts was found (P < 0.05). However, mtDNA content experimented a significantly increased along the later culture hours achieving the original mtDNA levels before vitrification after 4–5 h of culture (P < 0.05). Gene expression analysis and functional enrichment analysis revealed that such recovery was accompanied by upregulation of pathways associated with embryo developmental capacity and uterine embryo development. Interestingly, the significant increase in mtDNA content observed in blastocysts just after warming also coincided with the differential expression of several cellular stress response-related pathways, such as apoptosis, DNA damage, humoral immune responses, and cancer.

Conclusion

To our knowledge, this is the first study demonstrating in humans, a modulation in blastocysts mtDNA content in response to vitrification and warming. These results will be useful in understanding which pathways and mechanisms may be activated in human blastocysts following vitrification and warming before a transfer.

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Data availability

Data regarding any of the subjects in the study have not been previously published.

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Acknowledgements

The authors are grateful to all the embryologists of the IVF lab of IVIRMA Valencia.

Funding

This project was supported by the intramural funds of IVIRMA Global (Valencia), a grant from the IVI foundation (Instituto de Investigación Sanitaria La Fe, Valencia), and a grant for the recruitment of support staff in a technology transfer project (APOTI, Generalitat Valenciana).

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Authors and Affiliations

  1. IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106 - Torre A, Planta 1ª, 46026, Valencia, Spain

    Marta Pérez-Sánchez, Maria Luisa Pardiñas, Alicia Quiñonero, Francisco Domínguez & Angel Martin

  2. Department of Research, Igenomix, Parque Tecnológico, Rda. de Narcís Monturiol, nº11, B, 46980, Paterna, Valencia, Spain

    Antonio Díez-Juan

  3. Department of Gynaecology, IVIRMA Global, Plaça de La Policía Local, 3, Valencia, 46015, Spain

    Carmina Vidal

  4. IVF Laboratory, IVIRMA Global, Plaça de La Policía Local, 3, 46015, Valencia, Spain

    Diana Beltrán, Amparo Mifsud, Amparo Mercader, Ana Cobo & Maria José de los Santos

  5. Department of Gynaecology, IVIRMA Global, Largo Ildebrando Pizzetti, 1, Rome, 00197, Italy

    Antonio Pellicer

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  1. Marta Pérez-Sánchez
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Contributions

All authors have materially participated in the research and/or article preparation. (1) M. Pérez-Sánchez, ML. Pardiñas, A. Díez-Juan, A. Quiñonero, A. Martin, MJ. de los Santos: the conception and design of the study, or acquisition of data, or analysis and interpretation of data. (2) M. Pérez-Sánchez, ML. Pardiñas, F. Dominguez, A. Martin, MJ. de los Santos: drafting the article or revising it critically for important intellectual content. (3) C. Vidal, D. Beltran, A. Mifsud, A. Mercader, A. Pellicer, A. Cobo, MJ. de los Santos: final approval of the version to be submitted.

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Correspondence to Maria José de los Santos.

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Pérez-Sánchez, M., Pardiñas, M.L., Díez-Juan, A. et al. The effect of vitrification on blastocyst mitochondrial DNA dynamics and gene expression profiles. J Assist Reprod Genet 40, 2577–2589 (2023). https://doi.org/10.1007/s10815-023-02952-3

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