Testing the safety of MitoQ as a potential therapeutic to improve gamete quality and embryo development — ASN Events
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  3. Testing the safety of MitoQ as a potential therapeutic to improve gamete quality and embryo development

Testing the safety of MitoQ as a potential therapeutic to improve gamete quality and embryo development (#476)

Milana Frost 1 , Yasmyn Winstanley 1 , Rebecca Robker 1
  1. Robinson Research Institute, Adelaide University, Adelaide, SA, Australia
  1. Background:

The increasing age of first-time parents is associated with declining fertility that is commonly linked with gamete mitochondrial dysfunction. Current assisted reproductive technologies, including in vitro fertilisation, cannot improve gamete quality, highlighting the need for interventions enhancing mitochondrial function. MitoQ, a mitochondria-targeted antioxidant, is known to reduce oxidative damage and improve mitochondrial performance in various cell types. However, its safety and efficacy in gametes remain unclear, with inconsistent findings and limited investigation into clinically relevant treatment windows.

  1. Methods:

This study utilised mice to identify indications of toxicity in gametes and embryos after exposure to MitoQ. Oocytes were treated (1-hour) with 0-500nM MitoQ prior to IVF. Spermatozoa were treated during capacitation (1-hour) with 9 MitoQ doses, ranging 0-20µM, before CASA assessment for motility, progressive motility and hyperactivity. CASA data was analysed using Dunnett's Multiple Comparisons test or 2-way-ANOVA Tukey’s post hoc test (0-1µM n=10, 2.5-20µM n=8, 40-80µM n=2). Treated gametes underwent IVF, and on-time development was assessed (n=3 independent experiments). Blastocysts underwent immunohistochemistry (Oct3/4 and CDX2) for cell population quantification. Embryo developmental outcomes were assessed using 1-way-ANOVA Tukey’s post hoc test.

  1. Results:

Oocyte pre-IVF treatment with MitoQ did not affect developmental competence or blastocyst cell numbers. Spermatozoa motility (total and progressive) increased with 0.5µM MitoQ (P=0.0256) when compared to untreated controls, but decreased with 20µM (P=0.0015), indicative of toxicity. Oocytes fertilised by spermatozoa treated with 0.5µM MitoQ developed identically to controls, while fertilisation with 20µM MitoQ treated spermatozoa decreased 2-cell and blastocyst development (P=0.009), but did not alter cell numbers.

  1. Conclusion:

This study highlights that while low doses of MitoQ benefit gamete quality, high-dose exposure reduces motility and embryo development. This study provides preclinical data on the safety of MitoQ as a therapeutic for gamete quality, highlighting that dose selection is a critical issue.