A preclinical evaluation towards the clinical application of oxygen consumption measurement by CERMs by a mouse chimera model

Takashi Kuno, Masahito Tachibana, Ayako Fujimine-Sato, Misaki Fue, Keiko Higashi, Aiko Takahashi, Hiroki Kurosawa, Keisuke Nishio, Naomi Shiga, Zen Watanabe, Nobuo Yaegashi

Research output: Contribution to journalArticle

Abstract

We have developed an automated device for the measurement of oxygen consumption rate (OCR) called Chip-sensing Embryo Respiratory Measurement system (CERMs). To verify the safety and the significance of the OCR measurement by CERMs, we conducted comprehensive tests using a mouse model prior to clinical trials in a human in vitro fertilization (IVF) program. Embryo transfer revealed that the OCR measured by CERMs did not compromise the full-term development of mice or their future fertility, and was positively correlated with adenosine triphosphate (ATP) production and the mitochondrial membrane potential (∆Ψm), thereby indirectly reflecting mitochondrial oxidative phosphorylation (OXPHOS) activity. We demonstrated that the OCR is independent of embryo morphology (the size) and number of mitochondria (mitochondrial DNA copy number). The OCR correlated with the total cell numbers, whereas the inner cell mass (ICM) cell numbers and the fetal developmental rate were not. Thus, the OCR may serve as an indicator of the numbers of trophectoderm (TE) cells, rather than number or quality of ICM cells. However, implantation ability was neither correlated with the OCR, nor the embryo size in this model. This can probably be attributed to the limitation that chimeric embryos contain non-physiological high TE cells counts that are beneficial for implantation. CERMs can be safely employed in clinical IVF owing to it being a safe, highly effective, non-invasive, accurate, and quantitative tool for OCR measurement. Utilization of CERMs for clinical testing of human embryos would provide further insights into the nature of oxidative metabolism and embryonic viability.

Original languageEnglish
Article number5650
JournalInternational journal of molecular sciences
Volume20
Issue number22
DOIs
Publication statusPublished - 2019 Nov 2

Keywords

  • Adenosine triphosphate (ATP)
  • Assisted reproductive technology
  • Chimera
  • Embryo evaluation
  • Mitochondria
  • Oxygen consumption rate

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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