Skip to main content

Advertisement

Log in

Understanding mechanisms of oocyte development by follicular fluid lipidomics

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The present study aimed to provide a non-invasive approach to studying mechanisms responsible for oocyte development.

Methods

To this end, follicular fluid (FF) from 62 patients undergoing in vitro fertilization (IVF) cycles was split into two groups depending on the pregnancy outcome: pregnant (n = 28) and non-pregnant (n = 34) groups. Data were acquired by the MALDI-TOF mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to the data set. A ROC curve, to predict success rate, was constructed, and the lipids were attributed.

Results

Six ions were differentially represented in FF of pregnant and non-pregnant patients, with an area under the curve of 0.962. Phosphatidic acid, phosphatidylglycerol, and triacylglycerol were hyper-represented in the pregnant group, while glucosylceramide was hyper-represented in the non-pregnant group. Enriched functions related to these lipids are steroidogenesis, cellular response, signal transduction, cell cycle, and activation of protein kinase C for the pregnant group and apoptosis inhibition for the non-pregnant group.

Conclusion

Human FF fingerprinting can both improve the understanding concerning mechanisms responsible for oocyte development and its effect on embryo implantation potential and assist in the management of IVF cycles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sullivan EA, Zegers-Hochschild F, Mansour R, Ishihara O, de Mouzon J, Nygren KG, et al. International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report: assisted reproductive technology 2004. Hum Reprod. 2013;28(5):1375–90.

    Article  CAS  PubMed  Google Scholar 

  2. Sunkara SK, LaMarca A, Polyzos NP, Seed PT, Khalaf Y. Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data. Hum Reprod. 2016;31(10):2261–7.

    Article  PubMed  Google Scholar 

  3. Russell DL, Rodgers RJ. Riding the wave: determining the hierarchy of ovarian follicle activation. Biol Reprod. 2015;93(4):99.

    Article  CAS  PubMed  Google Scholar 

  4. Rodgers RJ, Irving-Rodgers HF. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod. 2010;82(6):1021–9.

    Article  CAS  PubMed  Google Scholar 

  5. Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V, et al. A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 2008;14(12):711–9.

    Article  CAS  PubMed  Google Scholar 

  6. Aydiner F, Yetkin CE, Seli E. Perspectives on emerging biomarkers for non-invasive assessment of embryo viability in assisted reproduction. Curr Mol Med. 2010;10(2):206–15.

    Article  CAS  PubMed  Google Scholar 

  7. Uyar A, Torrealday S, Seli E. Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril. 2013;99(4):979–97.

    Article  CAS  PubMed  Google Scholar 

  8. van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010;16(6):577–89.

    Article  PubMed  Google Scholar 

  9. Han X, Gross RW. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev. 2005;24(3):367–412.

    Article  CAS  PubMed  Google Scholar 

  10. Oresic M, Hanninen VA, Vidal-Puig A. Lipidomics: a new window to biomedical frontiers. Trends Biotechnol. 2008;26(12):647–52.

    Article  CAS  PubMed  Google Scholar 

  11. Postle AD. Lipidomics. Curr Opin Clin Nutr Metab Care. 2012;15(2):127–33.

    CAS  PubMed  Google Scholar 

  12. Want EJ, Cravatt BF, Siuzdak G. The expanding role of mass spectrometry in metabolite profiling and characterization. Chembiochem. 2005;6(11):1941–51.

    Article  CAS  PubMed  Google Scholar 

  13. Schwudke D, Oegema J, Burton L, Entchev E, Hannich JT, Ejsing CS, et al. Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition. Anal Chem. 2006;78(2):585–95.

    Article  CAS  PubMed  Google Scholar 

  14. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37(8):911–7.

    Article  CAS  PubMed  Google Scholar 

  15. Leroy JL, Vanholder T, Delanghe JR, Opsomer G, Van Soom A, Bols PE, et al. Metabolic changes in follicular fluid of the dominant follicle in high-yielding dairy cows early post partum. Theriogenology. 2004;62(6):1131–43.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang P, Fang L, Wu H, Ding P, Shen Q, Liu R. Down-regulation of GRalpha expression and inhibition of its nuclear translocation by hypoxia. Life Sci. 2016;146:92–9.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang JY, Diao YF, Oqani RK, Han RX, Jin DI. Effect of endoplasmic reticulum stress on porcine oocyte maturation and parthenogenetic embryonic development in vitro. Biol Reprod. 2012;86(4):128.

    PubMed  Google Scholar 

  18. Wang J, Qi L, Huang S, Zhou T, Guo Y, Wang G, et al. Quantitative phosphoproteomics analysis reveals a key role of insulin growth factor 1 receptor (IGF1R) tyrosine kinase in human sperm capacitation. Mol Cell Proteomics. 2015;14(4):1104–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mendelson CR, Jiang B, Shelton JM, Richardson JA, Hinshelwood MM. Transcriptional regulation of aromatase in placenta and ovary. J Steroid Biochem Mol Biol. 2005;95(1–5):25–33.

    Article  CAS  PubMed  Google Scholar 

  20. Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino Y. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. 2000;141(4):1317–24.

    Article  CAS  PubMed  Google Scholar 

  21. Piontkewitz Y, Sundfeldt K, Hedin L. The expression of c-myc during follicular growth and luteal formation in the rat ovary in vivo. J Endocrinol. 1997;152(3):395–406.

    Article  CAS  PubMed  Google Scholar 

  22. Bashir ST, Ishak GM, Gastal MO, Roser JF, Gastal EL. Changes in intrafollicular concentrations of free IGF-1, activin A, inhibin A, VEGF, estradiol, and prolactin before ovulation in mares. Theriogenology. 2016;85(8):1491–8.

    Article  CAS  PubMed  Google Scholar 

  23. Belin F, Goudet G, Duchamp G, Gerard N. Intrafollicular concentrations of steroids and steroidogenic enzymes in relation to follicular development in the mare. Biol Reprod. 2000;62(5):1335–43.

    Article  CAS  PubMed  Google Scholar 

  24. Rosenfeld CS, Wagner JS, Roberts RM, Lubahn DB. Intraovarian actions of oestrogen. Reproduction. 2001;122(2):215–26.

    Article  CAS  PubMed  Google Scholar 

  25. Ginther OJ, Gastal EL, Gastal MO, Beg MA. Regulation of circulating gonadotropins by the negative effects of ovarian hormones in mares. Biol Reprod. 2005;73(2):315–23.

    Article  CAS  PubMed  Google Scholar 

  26. Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012;18(1):73–91.

    Article  PubMed  Google Scholar 

  27. Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ. Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology. 2011;152(11):4377–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010;330(6002):366–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Richard S, Baltz JM. Prophase I arrest of mouse oocytes mediated by natriuretic peptide precursor C requires GJA1 (connexin-43) and GJA4 (connexin-37) gap junctions in the antral follicle and cumulus-oocyte complex. Biol Reprod. 2014;90(6):137.

    Article  CAS  PubMed  Google Scholar 

  30. Babeu JP, Boudreau F. Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J Gastroenterol. 2014;20(1):22–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Harris SE, Leese HJ, Gosden RG, Picton HM. Pyruvate and oxygen consumption throughout the growth and development of murine oocytes. Mol Reprod Dev. 2009;76(3):231–8.

    Article  CAS  PubMed  Google Scholar 

  32. Hresko RC, Kraft TE, Quigley A, Carpenter EP, Hruz PW. Mammalian glucose transporter activity is dependent upon anionic and conical phospholipids. J Biol Chem. 2016;291(33):17271–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes. 2001;50(8):1771–7.

    Article  CAS  PubMed  Google Scholar 

  34. Kurat CF, Wolinski H, Petschnigg J, Kaluarachchi S, Andrews B, Natter K, et al. Cdk1/Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression. Mol Cell. 2009;33(1):53–63.

    Article  CAS  PubMed  Google Scholar 

  35. Ruvolo PP. Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia. 2001;15(8):1153–60.

    Article  CAS  PubMed  Google Scholar 

  36. Bourbon NA, Yun J, Kester M. Ceramide directly activates protein kinase C zeta to regulate a stress-activated protein kinase signaling complex. J Biol Chem. 2000;275(45):35617–23.

    Article  CAS  PubMed  Google Scholar 

  37. Ruvolo PP, Clark W, Mumby M, Gao F, May WS. A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function. J Biol Chem. 2002;277(25):22847–52.

    Article  CAS  PubMed  Google Scholar 

  38. Liu YY, Han TY, Giuliano AE, Cabot MC. Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. J Biol Chem. 1999;274(2):1140–6.

    Article  CAS  PubMed  Google Scholar 

  39. Degroote S, Wolthoorn J, van Meer G. The cell biology of glycosphingolipids. Semin Cell Dev Biol. 2004;15(4):375–87.

    Article  CAS  PubMed  Google Scholar 

  40. Eggens I, Fenderson BA, Toyokuni T, Hakomori S. A role of carbohydrate-carbohydrate interaction in the process of specific cell recognition during embryogenesis and organogenesis: a preliminary note. Biochem Biophys Res Commun. 1989;158(3):913–20.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors wish to acknowledge the Coordination for the Improvement of Higher Education Personnel (CAPES) for providing funding for this research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniela Paes de Almeida Ferreira Braga.

Ethics declarations

Ethical Approval

The study received approval by the Ethics in Research Committee of Federal University of São Paulo.

Informed Consent

All participants included in the study provided the Informed consent form.

Disclaimer

The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Montani, D.A., Braga, D.P.d.F., Borges, E. et al. Understanding mechanisms of oocyte development by follicular fluid lipidomics. J Assist Reprod Genet 36, 1003–1011 (2019). https://doi.org/10.1007/s10815-019-01428-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-019-01428-7

Keywords

Navigation