Analysis of human embryo culture medium metabolites


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Abstract

Aim. To investigate metabolites of spent embryo culture media, including those containinggranulocyte-macrophage colony-stimulating factor (GM-CSF), and identify molecular profiles that enable prediction of the human embryo implantation potential. Materials and methods. We used samples of spent human embryo culture media with and without GM-CSF. The embryos were obtained from patients undergoing an IVF (ICSI). Metabolites were detected in the spent human embryo culture media using the HPLC-MS in the positive ion detection mode. After identifying chromatographic peaks, alignment of chromatograms, and better visualization of metabolite profiles in the compared samples, we conducted partial least squares discriminant analysis. Results. Metabolic profiling enabled the detection of significant differences between the spent human embryo culture media of implanted and non-implanted embryos, regardless of the culture medium type. We identified molecular ions which levels were significantly changed in the culture media of the implanted embryos. A comparative analysis of potential metabolites in culture media showed that the presence of GM-CSF could potentially affect the metabolism of fatty acids in implanted embryos. The regulation of the metabolism of fatty acids involved in structural, nutritional, and signaling functions plays an essential role in early embryonic development. Therefore, the presence of GM- CSF in the culture medium can facilitate adequate embryonic development and exert a positive effect on implantation potential. Conclusion. Metabolomic profiling of embryo culture media constituents offers a more accurate selection for elective single-embryo transfer to reduce the risks associated with multiple pregnancies.

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About the authors

Svetlana A. Yarygina

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: s.a.iarygina@yandex.ru
Ph.D. Student at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility

Veronika Yu. Smolnikova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: veronika.smolnikova@mail.ru
PhD, leading researcher, Department of Assistive Technologies in Infertility Treatment

Elena A. Kalinina

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
M.D., PhD, Head of IVF Department

Chupalav M. Eldarov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Ph.D. in Chemistry, Senior Researcher at the Laboratory of Molecular Pathophysiology

Alina M. Gamisonia

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; M.M. Shemyakin - Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the RAS

Researcher at the Laboratory of Molecular Pathophysiology

Natalia P. Makarova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: np_makarova@oparina4.ru
Dr. Biol. Sci., Senior Researcher at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility

Mikhail Yu. Bobrov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; M.M. Shemyakin - Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the RAS

Email: mbobr@mail.ru
Ph.D. in Chemistry, Head of the Laboratory of Molecular Pathophysiology

References

  1. Malina A., Pooley J.A. Psychological consequences of IVF fertilization. Review of research. Ann. Agric. Environ. Med. 2017; 24(4): 554-8. https://dx.doi. org/10.5604/12321966.1232085.
  2. Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy. Fertil. Steril. 2012; 97(4): 825-34. https://dx.doi.org/10.1016/j.fertnstert.2011.11.048.
  3. Sullivan E.A., Wang Y.A., Hayward I., Chambers G.M., Illingworth P., McBain J., Norman R.J. Single embryo transfer reduces the risk of perinatal mortality, a population study. Hum. Reprod. 2012; 27(12): 3609-15. https://dx.doi. org/10.1093/humrep/des315.
  4. Wang Q., Sun Q.Y. Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reprod. Fertil. Dev. 2007; 19: 1-12. https://dx.doi. org/10.1071/rd06103.
  5. Cimadomo D., Capalbo A., Ubaldi F.M., Scarica C., Palagiano A., Canipari R., Rienzi L. The impact of biopsy on human embryo developmental potential during preimplantation genetic diagnosis. Biomed. Res. Int. 2016; 2016: 7193075. https://dx.doi.org/10.1155/2016/7193075.
  6. Chen M., Wei S., Hu J., Quan S. Can comprehensive chromosome screening technology improve IVF/ICSI outcomes? A meta-analysis. PLoS One. 2015; 10(10): e0140779. https://dx.doi.org/10.1371/journal.pone.0140779.
  7. Houghton F.D., Hawkhead J.A., Humpherson P.G., Hogg J.E., Balen A.H., Rutherford A.J., Leese H.J. Non-invasive amino acid turnover predicts human embryo developmental capacity. Hum. Reprod. 2002; 17(4): 999-1005. https:// dx.doi.org/10.1093/humrep/17.4.999.
  8. Gardner D.K., Lane M., Stevens J., Schoolcraft W.B. Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential. Fertil. Steril. 2001; 76(6): 1175-80. https://dx.doi.org/10.1016/s0015-0282(01)02888-6.
  9. Vergouw C.G., Botros L.L., Judge K., Henson M., Roos P., Kostelijk E.H. et al. Non-invasive viability assessment of day-4 frozen-thawed human embryos using near infrared spectroscopy. Reprod. Biomed. Online. 2011; 23(6): 769-76. https://dx.doi.org/10.1016/j.rbmo.2011.08.015.
  10. Uyar A., Seli E. Embryo assessment strategies and their validation for clinical use: a critical analysis of methodology. Curr. Opin. Obstet. Gynecol. 2012; 24(3): 141-50. https://dx.doi.org/10.1097/GCO.0b013e328352cd17.
  11. Robertson S.A., Chin P.Y., Femia J.G., Brown H.M. Embryotoxic cytokines - Potential roles in embryo loss and fetal programming. J. Reprod. Immunol. 2018; 125: 80-8. https://dx.doi.org/10.1016/ j.jri.2017.12.003.
  12. Kawamura K., Chen Y., Shu Y., Cheng Y., Qiao J., Behr B. et al. Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine - growth factors. PLoS One. 2012; 7(11): e49328. https:// dx.doi.org/10.1371/journal.pone.0049328.
  13. Sjoblom C., Wikland M., Robertson S.A. Granulocyte-macrophage colony-stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos. Biol. Reprod. 2002; 67(6): 1817-23. https://dx.doi.org/10.1095/ biolreprod.101.001503.
  14. Morbeck D.E., Krisher R.L., Herrick J.R., Baumann N.A., Matern D., Moyer T. Composition of commercial media used for human embryo culture. Fertil. Steril. 2014; 102(3): 759-66. https://dx.doi.org/10.1016/j.fertnstert.2014.05.043.
  15. Sunde A., Balaban B. The assisted reproductive technology laboratory: toward evidence-based practice. Fertil. Steril. 2013; 100(2): 310-18. https://dx.doi. org/10.1016/j.fertnstert.2013.06.032.
  16. Vergouw C.G., Botros L.L., Roos P., Lens J.W., Schats R., Hompes PG. et al. Metabolomic profiling by near-infrared spectroscopy as a tool to assess embryo viability: a novel, noninvasive method for embryo selection. Hum. Reprod. 2008; 23(7): 1499-504. https://dx.doi.org/10.1093/humrep/den111.
  17. Seli E., Sakkas D., Scott R., Kwok S.C., Rosendahl S.M., Burns D.H. Noninvasive metabolomic profiling of embryo culture media using; Raman and near-infrared spectroscopy correlates with reproductive potential of embryos in women undergoing in vitro fertilization. Fertil. Steril. 2007; 88(5): 1350-7. https:// dx.doi.org/10.1016/j.fertnstert.2007.07.1390.
  18. Scott R., Seli E., Miller K., Sakkas D., Scott K., Burns D.H. Fertil. Steril. 2008; 90(1): 77-83. https://dx.doi.org/10.1016/j.fertnstert.2007.11.058.
  19. Rinaudo P., Shen S., Hua J., Qian S., Prabhu U., Garcia E. et al. H-1 NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos. J. Assist. Reprod. Genet. 2012; 29(12): 1435-42. https://dx.doi. org/10.1007/s10815-012-9877-9.
  20. Gode F., Akarsu S., Gunnur Dikmen Z., Tamer B., Isik A.Z. The effect follicular fluid vitamin A, E, D and B6 on embryo morphokinetics and pregnancy rates in patients receiving assisted reproduction. Gynecol. Obstet. Reprod. Med. 2019; 25(2): 89-95. https://dx.doi.org/10.21613/GORM.2018.860.
  21. Picton H.M., Elder K., Houghton F.D., Hawkhead J.A., Rutherford A.J., Hogg J.E. et al. Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro. Mol. Hum. Reprod. 2010; 16(8): 557-69. https://dx.doi.org/10.1093/molehr/gaq040.
  22. Richter K.S. The importance of growth factors for preimplantation embryo development and in-vitro culture. Curr. Opin. Obstet. Gynecol. 2008; 20(3): 292-304. https://dx.doi.org/10.1097/GCO.0b013e3282fe743b.
  23. Na Y.R., Gu G.J., Jung D., Kim Y.W Na J., Woo J.S. et al. GM-CSF induces inflammatory macrophages by regulating glycolysis and lipid metabolisms J. Immunol. 2016; 197(10): 4101-9. https://dx.doi.org/10.4049/ jimmunol.1600745.
  24. Kim I.K., Koh C.H., Jeon I., Shin K.S., Kang T.S., Bae E.A. et al. GM-CSF promotes antitumor immunity by inducing Th9 cell responses. Cancer Immunol. Res. 2019; 7(3): 498-509. https://dx.doi.org/10.1158/2326-6066.CIR-18-0518.
  25. Kennedy T. Interactions of eicosanoids and other factors in blastocyst implantation. In: Hillier K., ed. Eicosanoids and reproduction. Springer; 2012: 73-88. https://dx.doi.org/10.1007/978-94-009-3215-9.
  26. Yagi A., Miyanaga S., Shrestha R., Takeda S., Kobayashi S., Chiba H. et al. A fatty acid profiling method using liquid chromatography-high resolution mass spectrometry for improvement of assisted reproductive technology. Clin. Chim. Acta. 2016; 456: 100-6. https://dx.doi.org/10.1016/j.cca.2016.03.001.

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