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Gene expression analysis of follicular cells revealed inflammation as a potential IVF failure cause

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. Not every patient has the same response to the same treatment and many fail for unknown reasons. Knowing why a cycle has failed and how the follicles were affected would allow clinicians to adapt the treatment accordingly and improve success rate. This study examines the hypothesis that transcriptomic analysis of follicular cells from failed IVF cycles reveals potential reasons for failure and provides new information on the physiological mechanisms related to IVF failure.

Methods

Follicular cells (granulosa cells) were obtained from IVF patients of four Canadian fertility clinics. Using microarray analysis, patients that did not become pregnant following the IVF cycle were compared to those that did. Functional analysis was performed using ingenuity pathway analysis and qRT-PCR was used to validate the microarray results in a larger cohort of patients.

Results

The microarray showed 165 differentially expressed genes (DEGs) in the negative group compared to the pregnancy group. DEGs include many pro-inflammatory cytokines and other factors related to inflammation, suggesting that this process might be altered when IVF fails. Overexpression of several factors, some of which act upstream from vascular endothelial growth factor (VEGF), also indicates increased permeability and vasodilation. Some DEGs were related to abnormal differentiation and increased apoptosis.

Conclusions

Our results suggest that failure to conceive following IVF cycles could be associated with an imbalance between pro-inflammatory and anti-inflammatory mediators. The findings of this study identify potential failure causes and pathways for further investigation. Stimulatory protocols personalized according to patient response could improve the chances of later success.

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References

  1. Canadian Fertility and Andrology Society. Canadian ART Report. Human Assisted Reproduction 2014 Live Birth Rates for Canada 2014.

  2. The European IVF-Monitoring Consortium for the European Society of Human Reproduction and Embryology, Calhaz-Jorge C, de Geyter C, Kupka MS, de Mouzon J, Erb K, et al. Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE. Hum Reprod. 2016;31(8):1638–52. https://doi.org/10.1093/humrep/dew151.

    Article  Google Scholar 

  3. Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122(6):829–38.

    Article  CAS  Google Scholar 

  4. Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002;296(5576):2178–80. https://doi.org/10.1126/science.1071965.

    Article  CAS  PubMed  Google Scholar 

  5. Hamel M, Dufort I, Robert C, Gravel C, Leveille M-C, Leader A, et al. Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod. 2008;23(5):1118–27. https://doi.org/10.1093/humrep/den048.

    Article  CAS  PubMed  Google Scholar 

  6. Hamel M, Dufort I, Robert C, Léveillé M-C, Leader A, Sirard M-A. Genomic assessment of follicular marker genes as pregnancy predictors for human IVF. Mol Hum Reprod. 2010;16(2):87–96. https://doi.org/10.1093/molehr/gap079.

    Article  CAS  PubMed  Google Scholar 

  7. Hamel M, Dufort I, Robert C, Léveillé M-C, Leader A, Sirard M-A. Identification of follicular marker genes as pregnancy predictors for human IVF: new evidence for the involvement of luteinization process. Mol Hum Reprod. 2010;16(8):548–56. https://doi.org/10.1093/molehr/gaq051.

    Article  CAS  PubMed  Google Scholar 

  8. Uyar A, Torrealday S, Seli E. Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril. 2013;99(4):979–97. https://doi.org/10.1016/j.fertnstert.2013.01.129.

    Article  CAS  PubMed  Google Scholar 

  9. Burnik Papler T, Vrtacnik Bokal E, Maver A, Lovrecic L. Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod BioMed Online. 2015;30:426–33. https://doi.org/10.1016/j.rbmo.2014.12.011.

    Article  CAS  PubMed  Google Scholar 

  10. Gebhardt KM, Feil DK, Dunning KR, Lane M, Russell DL. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril. 2011;96(1):47–52 e2. https://doi.org/10.1016/j.fertnstert.2011.04.033.

    Article  CAS  PubMed  Google Scholar 

  11. Iager AE, Kocabas AM, Otu HH, Ruppel P, Langerveld A, Schnarr P, et al. Identification of a novel gene set in human cumulus cells predictive of an oocyte’s pregnancy potential. Fertil Steril. 2013;99(3):745–52 e6. https://doi.org/10.1016/j.fertnstert.2012.10.041.

    Article  CAS  PubMed  Google Scholar 

  12. Wathlet S, Adriaenssens T, Segers I, Verheyen G, Van Landuyt L, Coucke W, et al. Pregnancy prediction in single embryo transfer cycles after ICSI using QPCR: validation in oocytes from the same cohort. PLoS One. 2013;8(4):e54226. https://doi.org/10.1371/journal.pone.0054226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Anderson RA, Sciorio R, Kinnell H, Bayne RA, Thong KJ, de Sousa PA, et al. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction. 2009;138(4):629–37. https://doi.org/10.1530/REP-09-0144.

    Article  CAS  PubMed  Google Scholar 

  14. Assidi M, Montag M, Van der Ven K, Sirard MA. Biomarkers of human oocyte developmental competence expressed in cumulus cells before ICSI: a preliminary study. J Assist Reprod Genet. 2011;28(2):173–88. https://doi.org/10.1007/s10815-010-9491-7.

    Article  PubMed  Google Scholar 

  15. 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. https://doi.org/10.1093/molehr/gan067.

    Article  CAS  PubMed  Google Scholar 

  16. Feuerstein P, Puard V, Chevalier C, Teusan R, Cadoret V, Guerif F, et al. Genomic assessment of human cumulus cell marker genes as predictors of oocyte developmental competence: impact of various experimental factors. PLoS One. 2012;7(7):e40449. https://doi.org/10.1371/journal.pone.0040449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nivet AL, Leveille MC, Leader A, Sirard MA. Transcriptional characteristics of different sized follicles in relation to embryo transferability: potential role of hepatocyte growth factor signalling. Mol Hum Reprod. 2016;22:475–84. https://doi.org/10.1093/molehr/gaw029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Blazejczyk M, Miron M, Nadon R. FlexArray: a statistical data analysis software for gene expression microarrays. Montreal, Canada: Genome Quebec 2007.

  19. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034.

    Article  Google Scholar 

  20. Espey LL. Ovulation as an inflammatory reaction—a hypothesis. Biol Reprod. 1980;22(1):73–106.

    Article  CAS  Google Scholar 

  21. Espey LL, Lipner H. Ovulation. In: Knobil E, Neill JD, editors. The physiology of reproduction. 1 ed. New-York, United-States.: Raven Press; 1994. p. 725–80.

  22. Espey LL, Bellinger AS, Healy JA. Ovulation: an inflammatory cascade of gene expression. In: Leung PCK, Adashi EY, editors. The ovary. 2 ed. San Diego, CA, United States: Elsevier Academic Press; 2004. p. 145–165.

  23. Adams J, Liu Z, Ren YA, Wun WS, Zhou W, Kenigsberg S, et al. Enhanced inflammatory transcriptome in the granulosa cells of women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2016;101(9):3459–68. https://doi.org/10.1210/jc.2015-4275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dahm-Kahler P, Runesson E, Lind AK, Brannstrom M. Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle. Mol Hum Reprod. 2006;12(1):1–6. https://doi.org/10.1093/molehr/gah256.

    Article  CAS  PubMed  Google Scholar 

  25. Carletti MZ, Christenson LK. Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles. Reproduction. 2009;137(5):843–55. https://doi.org/10.1530/REP-08-0457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kaur S, Archer KJ, Devi MG, Kriplani A, Strauss JF 3rd, Singh R. Differential gene expression in granulosa cells from polycystic ovary syndrome patients with and without insulin resistance: identification of susceptibility gene sets through network analysis. J Clin Endocrinol Metab. 2012;97(10):E2016–21. https://doi.org/10.1210/jc.2011-3441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yan SF, Fujita T, Lu J, Okada K, Shan Zou Y, Mackman N, et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med. 2000;6(12):1355–61. https://doi.org/10.1038/82168.

    Article  CAS  PubMed  Google Scholar 

  28. Beckmann AM, Wilce PA. Egr transcription factors in the nervous system. Neurochem Int. 1997;31(4):477–510 discussion 7-6.

    Article  CAS  Google Scholar 

  29. Khachigian LM, Collins T. Early growth response factor 1: a pleiotropic mediator of inducible gene expression. J Mol Med (Berl). 1998;76(9):613–6.

    Article  CAS  Google Scholar 

  30. Cavaillon JM. Cytokines in inflammation. C R Seances Soc Biol Fil. 1995;189(4):531–44.

    CAS  PubMed  Google Scholar 

  31. Okada M, Fujita T, Sakaguchi T, Olson KE, Collins T, Stern DM, et al. Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation. FASEB J. 2001;15(14):2757–9. https://doi.org/10.1096/fj.01-0490fje.

    Article  CAS  PubMed  Google Scholar 

  32. Silverman ES, De Sanctis GT, Boyce J, Maclean JA, Jiao A, Green FH, et al. The transcription factor early growth-response factor 1 modulates tumor necrosis factor-alpha, immunoglobulin E, and airway responsiveness in mice. Am J Respir Crit Care Med. 2001;163(3 Pt 1):778–85. https://doi.org/10.1164/ajrccm.163.3.2003123.

    Article  CAS  PubMed  Google Scholar 

  33. Brannstrom M. Potential role of cytokines in ovarian physiology: the case for interleukin-1. In: Leung PCK, Adashi EY, editors. The ovary. 2 ed. San Diego, CA, United States: Elsevier Academic Press; 2004. p. 261–271.

  34. Guirao X, Lowry SF. Biologic control of injury and inflammation: much more than too little or too late. World J Surg. 1996;20(4):437–46.

    Article  CAS  Google Scholar 

  35. Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med. 1993;178(6):2207–11.

    Article  CAS  Google Scholar 

  36. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771–6. https://doi.org/10.1016/j.cell.2010.03.006.

    Article  CAS  PubMed  Google Scholar 

  37. Muszynski JA, Frazier WJ, Hall MW. Pro-inflammatory and anti-inflammatory mediators in critical illness and injury. In: Wheeler SD, Wong RH, Shanley PT, editors. Pediatric critical care medicine: volume 1: care of the critically ill or injured child. London: Springer London; 2014. p. 231–8.

    Chapter  Google Scholar 

  38. Haslett C. Granulocyte apoptosis and inflammatory disease. Br Med Bull. 1997;53(3):669–83.

    Article  CAS  Google Scholar 

  39. Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 2002;109(1):41–50. https://doi.org/10.1172/JCI11638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature. 1997;390(6658):350–1. https://doi.org/10.1038/37022.

    Article  CAS  PubMed  Google Scholar 

  41. McGrath EE, Marriott HM, Lawrie A, Francis SE, Sabroe I, Renshaw SA, et al. TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. J Leukoc Biol. 2011;90(5):855–65. https://doi.org/10.1189/jlb.0211062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Renshaw SA, Parmar JS, Singleton V, Rowe SJ, Dockrell DH, Dower SK, et al. Acceleration of human neutrophil apoptosis by TRAIL. J Immunol. 2003;170(2):1027–33.

    Article  CAS  Google Scholar 

  43. Bergh PA, Navot D. Ovarian hyperstimulation syndrome: a review of pathophysiology. J Assist Reprod Genet. 1992;9(5):429–38.

    Article  CAS  Google Scholar 

  44. McClure N, Healy DL, Rogers PA, Sullivan J, Beaton L, Haning RV Jr, et al. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet. 1994;344(8917):235–6.

    Article  CAS  Google Scholar 

  45. Soares SR, Gomez R, Simon C, Garcia-Velasco JA, Pellicer A. Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome. Hum Reprod Update. 2008;14(4):321–33. https://doi.org/10.1093/humupd/dmn008.

    Article  CAS  PubMed  Google Scholar 

  46. Vlahos NF, Gregoriou O. Prevention and management of ovarian hyperstimulation syndrome. Ann N Y Acad Sci. 2006;1092:247–64. https://doi.org/10.1196/annals.1365.021.

    Article  CAS  PubMed  Google Scholar 

  47. Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW. Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med. 2004;36(1):1–12. https://doi.org/10.1038/emm.2004.1.

    Article  PubMed  Google Scholar 

  48. Kim W, Moon SO, Sung MJ, Kim SH, Lee S, So JN, et al. Angiogenic role of adrenomedullin through activation of Akt, mitogen-activated protein kinase, and focal adhesion kinase in endothelial cells. FASEB J. 2003;17(13):1937–9. https://doi.org/10.1096/fj.02-1209fje.

    Article  CAS  PubMed  Google Scholar 

  49. Sugo S, Minamino N, Shoji H, Kangawa K, Kitamura K, Eto T, et al. Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem Biophys Res Commun. 1995;207(1):25–32. https://doi.org/10.1006/bbrc.1995.1148.

    Article  CAS  PubMed  Google Scholar 

  50. Ando M, Kol S, Kokia E, Ruutiainen-Altman K, Sirois J, Rohan RM, et al. Rat ovarian prostaglandin endoperoxide synthase-1 and -2: periovulatory expression of granulosa cell-based interleukin-1-dependent enzymes. Endocrinology. 1998;139(5):2501–8. https://doi.org/10.1210/endo.139.5.5988.

    Article  CAS  PubMed  Google Scholar 

  51. Levitas E, Chamoun D, Udoff LC, Ando M, Resnick CE, Adashi EY. Periovulatory and interleukin-1 beta-dependent up-regulation of intraovarian vascular endothelial growth factor (VEGF) in the rat: potential role for VEGF in the promotion of periovulatory angiogenesis and vascular permeability. J Soc Gynecol Investig. 2000;7(1):51–60.

    CAS  PubMed  Google Scholar 

  52. Smith-Mungo LI, Kagan HM. Lysyl oxidase: properties, regulation and multiple functions in biology. Matrix Biol. 1998;16(7):387–98.

    Article  CAS  Google Scholar 

  53. Baker AM, Bird D, Welti JC, Gourlaouen M, Lang G, Murray GI, et al. Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis. Cancer Res. 2013;73(2):583–94. https://doi.org/10.1158/0008-5472.CAN-12-2447.

    Article  CAS  PubMed  Google Scholar 

  54. Mammoto A, Mammoto T, Kanapathipillai M, Wing Yung C, Jiang E, Jiang A, et al. Control of lung vascular permeability and endotoxin-induced pulmonary oedema by changes in extracellular matrix mechanics. Nat Commun. 2013;4:1759. https://doi.org/10.1038/ncomms2774.

    Article  CAS  PubMed  Google Scholar 

  55. Vloeberghs V, Peeraer K, Pexsters A, D'Hooghe T. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol. 2009;23(5):691–709. https://doi.org/10.1016/j.bpobgyn.2009.02.006.

    Article  PubMed  Google Scholar 

  56. Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA Jr. Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion. Am J Pathol. 1985;121(3):394–403.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA Jr. Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985;76(5):2003–11. https://doi.org/10.1172/JCI112200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7(9):678–89. https://doi.org/10.1038/nri2156.

    Article  CAS  PubMed  Google Scholar 

  59. Nourshargh S, Alon R. Leukocyte migration into inflamed tissues. Immunity. 2014;41(5):694–707. https://doi.org/10.1016/j.immuni.2014.10.008.

    Article  CAS  PubMed  Google Scholar 

  60. Rizk B, Aboulghar M, Smitz J, Ron-El R. The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome. Hum Reprod Update. 1997;3(3):255–66.

    Article  CAS  Google Scholar 

  61. Wong GG, Clark SC. Multiple actions of interleukin 6 within a cytokine network. Immunol Today. 1988;9(5):137–9. https://doi.org/10.1016/0167-5699(88)91200-5.

    Article  CAS  PubMed  Google Scholar 

  62. Hammond ME, Lapointe GR, Feucht PH, Hilt S, Gallegos CA, Gordon CA, et al. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J Immunol. 1995;155(3):1428–33.

    CAS  PubMed  Google Scholar 

  63. Brannstrom M, Pascoe V, Norman RJ, McClure N. Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril. 1994;61(3):488–95.

    Article  CAS  Google Scholar 

  64. Norman R, Bonello N, Jasper M, Van der Hoek K. Leukocytes: essential cells in ovarian function and ovulation. Reprod Med Rev. 1997;6(02):97–111. https://doi.org/10.1017/S0962279900001447.

    Article  Google Scholar 

  65. Hock DL, Huhn RD, Kemmann E. Leukocytosis in response to exogenous gonadotrophin stimulation. Hum Reprod. 1997;12(10):2143–6.

    Article  CAS  Google Scholar 

  66. Fabregues F, Balasch J, Manau D, Jimenez W, Arroyo V, Creus M, et al. Haematocrit, leukocyte and platelet counts and the severity of the ovarian hyperstimulation syndrome. Hum Reprod. 1998;13(9):2406–10.

    Article  CAS  Google Scholar 

  67. Loret de Mola JR, Baumgardner GP, Goldfarb JM, Friedlander MA. Ovarian hyperstimulation syndrome: pre-ovulatory serum concentrations of interleukin-6, interleukin-1 receptor antagonist and tumour necrosis factor-alpha cannot predict its occurrence. Hum Reprod. 1996;11(7):1377–80.

    Article  CAS  Google Scholar 

  68. Bertout JA, Mahutte NG, Preston SL, Behrman HR. Reactive oxygen species and ovarian function. In: Leung PCK, Adashi EY, editors. The ovary. 2 ed. San Diego, CA, United States: Elsevier Academic Press; 2004. p. 353–368.

  69. Davisson MT, Bechtel LJ, Akeson EC, Fortna A, Slavov D, Gardiner K. Evolutionary breakpoints on human chromosome 21. Genomics. 2001;78(1–2):99–106. https://doi.org/10.1006/geno.2001.6639.

    Article  CAS  PubMed  Google Scholar 

  70. Nishizaki R, Ota M, Inoko H, Meguro A, Shiota T, Okada E, et al. New susceptibility locus for high myopia is linked to the uromodulin-like 1 (UMODL1) gene region on chromosome 21q22.3. Eye (Lond). 2009;23(1):222–9. https://doi.org/10.1038/eye.2008.152.

    Article  CAS  Google Scholar 

  71. Shibuya K, Nagamine K, Okui M, Ohsawa Y, Asakawa S, Minoshima S, et al. Initial characterization of an uromodulin-like 1 gene on human chromosome 21q22.3. Biochem Biophys Res Commun. 2004;319(4):1181–9. https://doi.org/10.1016/j.bbrc.2004.05.094.

    Article  CAS  PubMed  Google Scholar 

  72. Wang W, Tang Y, Ni L, Kim E, Jongwutiwes T, Hourvitz A, et al. Overexpression of uromodulin-like1 accelerates follicle depletion and subsequent ovarian degeneration. Cell Death Dis. 2012;3:e433. https://doi.org/10.1038/cddis.2012.169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rodriguez P, Vinuela JE, Alvarez-Fernandez L, Gomez-Marquez J. Prothymosin alpha antisense oligonucleotides induce apoptosis in HL-60 cells. Cell Death Differ. 1999;6(1):3–5. https://doi.org/10.1038/sj.cdd.4400450.

    Article  CAS  PubMed  Google Scholar 

  74. Jiang X, Kim HE, Shu H, Zhao Y, Zhang H, Kofron J, et al. Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science. 2003;299(5604):223–6. https://doi.org/10.1126/science.1076807.

    Article  CAS  PubMed  Google Scholar 

  75. Qi X, Wang L, Du F. Novel small molecules relieve prothymosin alpha-mediated inhibition of apoptosome formation by blocking its interaction with Apaf-1. Biochemistry. 2010;49(9):1923–30. https://doi.org/10.1021/bi9022329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Isabelle Dufort for her support and assistance in the lab, and Scot Hamilton, Marie-Claude Léveillé, Martin Laforest, and Hanane Lachgar for their involvement in the collection of follicle cell samples.

Authors’ roles

Fortin, C.: conception and design of the study, sample processing, data acquisition, data analysis and interpretation, drafting the article, approval of the final manuscript.

Leader, A.: data acquisition, critical discussion, reading and approval of the final manuscript.

Mahutte, N.: data acquisition, critical discussion, reading and approval of the final manuscript.

Hamilton, S.: data acquisition, critical discussion, reading and approval of the final manuscript.

Léveillé, M.C.: data acquisition, critical discussion, reading and approval of the final manuscript.

Villeneuve, M.: data acquisition, critical discussion, reading and approval of the final manuscript.

Sirard, M.A.: conception and design of the study, data analysis and interpretation, improvement of the draft, reading and approval of the final manuscript.

Funding

This work was supported by the Merck Serono Grant for Fertility Innovation (GFI).

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Authors and Affiliations

  1. Centre de recherche en reproduction, développement et santé intergénérationnelle (CRDSI), Université Laval, 2440 Boulevard Hochelaga, Québec, QC, G1V 0A6, Canada

    Chloé S. Fortin & Marc-André Sirard

  2. Ottawa Fertility Centre, 100-955 Green Valley Crescent, Ottawa, ON, K2C 3V4, Canada

    Arthur Leader & Marie-Claude Léveillé

  3. Montréal Fertility Centre, 5252 de Maisonneuve Boulevard West Suite 220, Montréal, QC, H4A 3S5, Canada

    Neal Mahutte

  4. Reproductive Care Centre, 2180 Meadowvale Boulevard, Toronto, ON, L5N 5S3, Canada

    Scot Hamilton

  5. PROCREA Cliniques, 5600 Boulevard des Galeries, Québec, QC, G2K 2H6, Canada

    Marc Villeneuve

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  1. Chloé S. Fortin
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Correspondence to Marc-André Sirard.

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The authors declare that they have no conflict of interest. A GFI grant was received in support of this work. This article does not contain any data or conclusion relating to any commercial product.

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This project was approved by Université Laval REB (2014-102/08-09-2014) for the collection and use of human tissues.

Large-scale data

The data discussed in this publication are accessible through GEO Series accession number GSE87545.

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Fortin, C., Leader, A., Mahutte, N. et al. Gene expression analysis of follicular cells revealed inflammation as a potential IVF failure cause. J Assist Reprod Genet 36, 1195–1210 (2019). https://doi.org/10.1007/s10815-019-01447-4

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