Early evidence of the artificial transfer/transplant of mitochondria to oocytes and zygotes by MitoCeption

Francisco Cabrera, Verónica Castañeda, Emilia Morales, Francesca Velarde, Mayra Ortega, Ariana Leon-Sosa, Christian Jorgensen, Andrés Caicedo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Oocytes may carry mutations in their mitochondrial DNA (mtDNA) which affect fertility and embryo development leading to hereditary diseases or rejection. Mitochondrial replacement therapies (MRTs) such as polar body transfer, spindle transfer and pronuclear transfer, aim to change dysfunctional to normal mitochondria inside oocytes and zygotes resulting in healthier offspring. Even with promising results, MRTs techniques are invasive to oocytes and may negatively affect their viability and the success of the procedure. This article shows early evidence of the use of MitoCeption, a mitochondria transfer/transplant (AMT/T) technique to possibly induce the internalization of exogenous mitochondria in a dose-dependent manner to recipient oocytes in comparison to coincubation. By using human isolated mitochondria in a mix obtained from different donors we were able to identify their mtDNA in murine oocytes by qPCR. Fluorescence microscopy showed that exogenous and transferred mitochondria (MitoTracker ® Red) by MitoCeption were internalized in oocytes and zygotes (CellTracker® Green). After maintaining mitocepted zygotes to two-cell embryos, we transferred them to subrogate female mice and obtained healthy mice pups; however, without clear evidence of the maintenance of human mtDNA in the tissues of mice pups. These early results are puzzling, and they open the path to generate more research regarding the use of MitoCeption in comparison to coincubation in order to transfer mitochondria to oocytes using less invasive procedures.

Original languageEnglish
Pages (from-to)102-112
Number of pages11
JournalMitochondrion
Volume65
DOIs
StatePublished - Jul 2022
Externally publishedYes

Bibliographical note

Funding Information:
We thank the School of Human and Veterinary Medicine at the Universidad San Francisco de Quito, USFQ, the “Instituto de Investigaciones en Biomedicina, USFQ”, and the Mito-Act Research Consortium in Quito, Ecuador for their constant support of our work and initiatives.

Publisher Copyright:
© 2022

Keywords

  • Coincubation
  • Heteroplasmy
  • MitoCeption
  • Mitochondria replacement therapy (MRT)
  • Mitochondrial disease
  • Oocytes
  • Xenogeneic transfer/transplant
  • Zygotes

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