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Antioxidants in preimplantation mouse embryo culture media and vitrification/warming solutions support a more in vivo-like gene expression profile in fetal liver and placenta post-transfer

Published:November 26, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.11.013

      Abstract

      Research question

      : What is the effect of combined antioxidants (acetyl-L-carnitine, N-acetyl-L-cysteine and α-lipoic acid; A3) when used in culture media and vitrification/warming solutions, on mouse fetal gene expression?

      Design

      : A laboratory-based analysis of an animal model. Embryo transfers were conducted on in vivo flushed blastocysts, or blastocysts cultured or vitrified with and without A3. Transcriptional profiles of E14 fetal liver and placental tissue in all groups were quantified using RNAseq and functional analyses (GO biological processes and KEGG pathway analysis).

      Results

      : Both in vitro culture in the presence of 20% oxygen and vitrification of blastocysts significantly perturbed fetal liver and placental gene expression. Notably, supplementation of in vitro culture media or vitrification/warming solutions with A3 reduced the number of DEGs and biological processes altered, establishing a more in vivo like gene expression profile, particularly within the E14.5 placenta. Specifically, A3 supplementation significantly reduced the expression of genes associated with preeclampsia and intrauterine growth restriction, along with genes involved in metabolism, cell senescence and cancer associated pathways. However, despite these improvements, several biological processes remained overrepresented following both in vitro culture and vitrification, even in the presence of A3.

      Conclusion

      : Both in vitro culture in the presence of 20% oxygen and vitrification of blastocysts significantly perturbed fetal liver and placental gene expression, with the number of DEGs greater following vitrification. Supplementation with A3 reduced the number of DEGs and biological processes altered, establishing a more in vivo like gene expression profile, particularly in the placenta. Notably, A3 supplementation of in vitro culture significantly reduced the expression of genes associated with preeclampsia and intrauterine growth restriction.

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      Biography

      Thi Truong is a senior research embryologist and laboratory manager in Professor David Gardner's ART laboratory at the University of Melbourne, Australia. She has over 14 years’ experience in embryology research. Her main interest is in discovering ways to improve ART outcomes through the use of antioxidants.