Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability

Stimulation of mitochondria in embryos from older mice improved embryo viability and fetal weights and therefore may be a novel means of improving outcomes in an IVF setting.

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Authors

Nicole O. McPherson, B.Hlth.Sc.(Hons.), Deirdre Zander, Ph.D., Michelle Lane, Ph.D.

Volume 101, Issue 5, Pages 1458–1466.e5

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.

Design:

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.

Setting:

University research facility.

Animal(s):

Swiss female mice 26- to 28-week-old.

Intervention(s):

The addition of DCA to the embryo culture media.

Main Outcome Measure(s):

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.

Result(s):

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.

Conclusion(s):

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00078-8/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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