title: Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability.
abstract: OBJECTIVE
  To determine whether supplementation of embryo culture media with a substrate to stimulate mitochondrial activity improves embryo viability and pregnancy establishment in aged mice.
  
  
  METHODS
  Female mice were superovulated and mated. Zygotes were collected and cultured in either G1/G2 or G1/G2 with 1.0 mM dichloroacetic acid (DCA), a stimulator of pyruvate dehydrogenase complex. Embryos were cultured to the blastocyst stage and transferred into pseudopregnant female mice.
  
  
  METHODS
  University research facility.
  
  
  METHODS
  Swiss female mice 26- to 28-week-old.
  
  
  METHODS
  The addition of DCA to the embryo culture media.
  
  
  METHODS
  Embryo development, total, trophectoderm, inner cell mass (ICM) and epiblast cell number, mitochondrial membrane potential, reactive oxygen species, pyruvate oxidation, adenosine triphosphate (ATP) output, implantation rates, and fetal and placental size and weights.
  
  
  RESULTS
  Supplementation of the embryo culture medium with DCA significantly increased blastocyst development rates in vitro, significantly improved total, trophectoderm, and ICM cell numbers and pluripotency of the ICM, significantly increased pyruvate oxidation and ATP output, and significantly increased fetal weights and size comparable to in vivo conditions.
  
  
  CONCLUSIONS
  This study demonstrates that the addition of DCA to embryo culture media improves mitochondrial output in embryos produced from aged mice. Although DCA itself may be of limited therapeutic value in a clinical setting due to its low threshold of dosage and high toxicity, this proof of concept study does suggest that the addition of a physiological-based mitochondrial stimulator to embryo culture media for aged women may potentially improve IVF outcomes.
authors.affiliation: School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia. Electronic address: nicole.mcpherson@adelaide.edu.au.
authors.forename: Nicole O
authors.initials: NO
authors.lastname: McPherson
authors.affiliation: School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia; Repromed, Dulwich, Adelaide, South Australia, Australia.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Zander-Fox
authors.affiliation: School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia; Repromed, Dulwich, Adelaide, South Australia, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lane
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004624:Embryo Transfer / Q000379:methods; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology*; D005260:Female; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D023421:Models, Animal; D010865:Pilot Projects; D011247:Pregnancy
chemical_list: D003999:Dichloroacetic Acid
keywords: Embryo development; IVF; mitochondrial medicine