#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts


Autoři: Helena Kaihola aff001;  Fatma Gülen Yaldir aff002;  Therese Bohlin aff003;  Raghad Samir aff004;  Julius Hreinsson aff001;  Helena Åkerud aff001
Působiště autorů: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden aff001;  Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden aff002;  Fertility Unit, Örebro University Hospital, Örebro, Sweden aff003;  Livio Fertility Centre Falun, Falun, Sweden aff004;  GynHälsan Fertility Clinic, Minerva Fertility, Uppsala, Sweden aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226419

Souhrn

Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ≤ 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ≤ 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ≤ 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.

Klíčová slova:

Embryos – Pregnancy – Apoptosis – Biomarkers – Culture media – Blastocysts – Embryo transfer


Zdroje

1. Embryology ESoHRa. More than 8 million babies born from IVF since the world's first in 1978: European IVF pregnancy rates now steady at around 36 percent, according to ESHRE monitoring.: ScienceDaily; 2018 [3 July 2018]. Available from: www.sciencedaily.com/releases/2018/07/180703084127.htm.

2. De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Human reproduction. 2018;33(9):1586–601. Epub 2018/07/23. doi: 10.1093/humrep/dey242 30032255.

3. Hardarson T, Van Landuyt L, Jones G. The blastocyst. Human reproduction. 2012;27 Suppl 1:i72–91. Epub 2012/07/06. doi: 10.1093/humrep/des230 22763375.

4. Gardner DK, Sakkas D. Assessment of embryo viability: the ability to select a single embryo for transfer—a review. Placenta. 2003;24 Suppl B:S5–12. Epub 2003/10/16. doi: 10.1016/s0143-4004(03)00136-x 14559024.

5. Balaban B. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Human reproduction. 2011;26(6):1270–83. Epub 2011/04/20. doi: 10.1093/humrep/der037 [pii]. 21502182.

6. Kaser DJ, Racowsky C. Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. Human reproduction update. 2014;20(5):617–31. Epub 2014/06/04. doi: 10.1093/humupd/dmu023 24890606.

7. Chen M, Wei S, Hu J, Yuan J, Liu F. Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials. PloS one. 2017;12(6):e0178720. Epub 2017/06/02. doi: 10.1371/journal.pone.0178720 28570713; PubMed Central PMCID: PMC5453598.

8. Armstrong S, Bhide P, Jordan V, Pacey A, Farquhar C. Time-lapse systems for embryo incubation and assessment in assisted reproduction. The Cochrane database of systematic reviews. 2018;5:Cd011320. Epub 2018/05/26. doi: 10.1002/14651858.CD011320.pub3 29800485.

9. Thompson JG, Brown HM, Sutton-McDowall ML. Measuring embryo metabolism to predict embryo quality. Reproduction, fertility, and development. 2016;28(1–2):41–50. Epub 2015/02/01. doi: 10.1071/RD15340 27062873.

10. Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014;101(6):1531–44. Epub 2014/06/03. doi: 10.1016/j.fertnstert.2014.04.023 24882617.

11. Rodgaard T, Heegaard PM, Callesen H. Non-invasive assessment of in-vitro embryo quality to improve transfer success. Reproductive biomedicine online. 2015;31(5):585–92. Epub 2015/09/19. doi: 10.1016/j.rbmo.2015.08.003 26380864.

12. Capalbo A, Ubaldi FM, Cimadomo D, Noli L, Khalaf Y, Farcomeni A, et al. MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment. Fertil Steril. 2016;105(1):225–35 e1-3. Epub 2015/10/11. doi: 10.1016/j.fertnstert.2015.09.014 26453979.

13. Gardner DK, Meseguer M, Rubio C, Treff NR. Diagnosis of human preimplantation embryo viability. Human reproduction update. 2015;21(6):727–47. Epub 2015/01/09. doi: 10.1093/humupd/dmu064 25567750.

14. Krisher RL, Schoolcraft WB, Katz-Jaffe MG. Omics as a window to view embryo viability. Fertil Steril. 2015;103(2):333–41. Epub 2015/02/03. doi: 10.1016/j.fertnstert.2014.12.116 25639968.

15. Vergouw CG, Heymans MW, Hardarson T, Sfontouris IA, Economou KA, Ahlstrom A, et al. No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis. Human reproduction. 2014;29(3):455–61. Epub 2014/01/11. doi: 10.1093/humrep/det456 24408316.

16. Munne S. Status of preimplantation genetic testing and embryo selection. Reproductive biomedicine online. 2018;37(4):393–6. Epub 2018/09/21. doi: 10.1016/j.rbmo.2018.08.001 30232021.

17. Kaihola H, Yaldir FG, Hreinsson J, Hornaeus K, Bergquist J, Olivier JD, et al. Effects of Fluoxetine on Human Embryo Development. Front Cell Neurosci. 2016;10:160. Epub 2016/07/06. doi: 10.3389/fncel.2016.00160 PubMed Central PMCID: PMC4909759. 27378857

18. Lindgren KE, Gulen Yaldir F, Hreinsson J, Holte J, Karehed K, Sundstrom-Poromaa I, et al. Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay. Upsala journal of medical sciences. 2018;123(3):143–52. Epub 2018/10/05. doi: 10.1080/03009734.2018.1490830 30282508; PubMed Central PMCID: PMC6198226.

19. Doseff AI. Apoptosis: the sculptor of development. Stem cells and development. 2004;13(5):473–83. Epub 2004/12/14. doi: 10.1089/scd.2004.13.473 15588505.

20. Nordqvist S, Karehed K, Hambiliki F, Wanggren K, Stavreus-Evers A, Akerud H. The presence of histidine-rich glycoprotein in the female reproductive tract and in embryos. Reproductive sciences (Thousand Oaks, Calif). 2010;17(10):941–7. Epub 2010/07/20. doi: 10.1177/1933719110374366 [pii]. 20639474.

21. Nordqvist S, Karehed K, Stavreus-Evers A, Akerud H. Histidine-rich glycoprotein polymorphism and pregnancy outcome: a pilot study. Reproductive biomedicine online. 2011;23(2):213–9. Epub 2011/06/15. doi: 10.1016/j.rbmo.2011.04.004 21665544.

22. Bolin M, Akerud P, Hansson A, Akerud H. Histidine-rich glycoprotein as an early biomarker of preeclampsia. American journal of hypertension. 2011;24(4):496–501. Epub 2011/01/22. doi: 10.1038/ajh.2010.264 21252863.

23. Granfors M, Karypidis H, Hosseini F, Skjoldebrand-Sparre L, Stavreus-Evers A, Bremme K, et al. Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: a retrospective case control study. BMC medical genetics. 2012;13:121. Epub 2012/12/15. doi: 10.1186/1471-2350-13-121 23237535; PubMed Central PMCID: PMC3556309.

24. Lindgren KE, Hreinsson J, Helmestam M, Wånggren K, Sundström Poromaa I, Kårehed K, et al. Histidine-rich glycoprotein derived peptides affect endometrial angiogenesis in vitro but has no effect on embryo development. Systems biology in reproductive medicine. 2016;In press.

25. Juarez JC, Guan X, Shipulina NV, Plunkett ML, Parry GC, Shaw DE, et al. Histidine-proline-rich glycoprotein has potent antiangiogenic activity mediated through the histidine-proline-rich domain. Cancer Res. 2002;62(18):5344–50. Epub 2002/09/18. 12235005.

26. Silverstein RL, Febbraio M. CD36-TSP-HRGP interactions in the regulation of angiogenesis. Current pharmaceutical design. 2007;13(35):3559–67. Epub 2008/01/29. doi: 10.2174/138161207782794185 18220792.

27. Lundberg M, Eriksson A, Tran B, Assarsson E, Fredriksson S. Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic acids research. 2011;39(15):e102. Epub 2011/06/08. doi: 10.1093/nar/gkr424 21646338; PubMed Central PMCID: PMC3159481.

28. Assarsson E, Lundberg M, Holmquist G, Björkesten J, Bucht Thorsen S, Ekman D, et al. Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent Scalability. PloS one. 2014;9(4):e95192. doi: 10.1371/journal.pone.0095192 24755770

29. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science (New York, NY). 1998;281(5381):1312–6. Epub 1998/08/28. doi: 10.1126/science.281.5381.1312 9721091.

30. Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell. 1997;89(2):175–84. Epub 1997/04/18. doi: 10.1016/s0092-8674(00)80197-x 9108473.

31. Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 1998;391(6662):96–9. Epub 1998/01/09. doi: 10.1038/34214 9422513

32. Jurisicova A, Antenos M, Varmuza S, Tilly JL, Casper RF. Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation. Molecular human reproduction. 2003;9(3):133–41. Epub 2003/02/28. doi: 10.1093/molehr/gag016 12606589.

33. Ubeda M, Habener JF. The large subunit of the DNA replication complex C (DSEB/RF-C140) cleaved and inactivated by caspase-3 (CPP32/YAMA) during Fas-induced apoptosis. The Journal of biological chemistry. 1997;272(31):19562–8. Epub 1997/08/01. doi: 10.1074/jbc.272.31.19562 9235961.

34. Samejima K, Villa P, Earnshaw WC. Role of factors downstream of caspases in nuclear disassembly during apoptotic execution. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 1999;354(1389):1591–8; discussion 8–9. Epub 1999/12/03. doi: 10.1098/rstb.1999.0503 10582245; PubMed Central PMCID: PMC1692664.

35. Leung LL. Interaction of histidine-rich glycoprotein with fibrinogen and fibrin. J Clin Invest. 1986;77(4):1305–11. Epub 1986/04/01. doi: 10.1172/JCI112435 3958188; PubMed Central PMCID: PMC424483.

36. Simantov R, Febbraio M, Crombie R, Asch AS, Nachman RL, Silverstein RL. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. J Clin Invest. 2001;107(1):45–52. Epub 2001/01/03. doi: 10.1172/JCI9061 11134179; PubMed Central PMCID: PMC198540.

37. Armstrong LC, Bornstein P. Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol. 2003;22(1):63–71. Epub 2003/04/26. S0945053X03000052 [pii]. doi: 10.1016/s0945-053x(03)00005-2 12714043.

38. Lin X, Beckers E, Mc Cafferty S, Gansemans Y, Joanna Szymanska K, Chaitanya Pavani K, et al. Bovine Embryo-Secreted microRNA-30c Is a Potential Non-invasive Biomarker for Hampered Preimplantation Developmental Competence. Frontiers in genetics. 2019;10:315. Epub 2019/04/27. doi: 10.3389/fgene.2019.00315 31024625; PubMed Central PMCID: PMC6459987.

39. Cimadomo D, Rienzi L, Giancani A, Alviggi E, Dusi L, Canipari R, et al. Definition and validation of a custom protocol to detect miRNAs in the spent media after blastocyst culture: searching for biomarkers of implantation. Human reproduction. 2019. Epub 2019/08/17. doi: 10.1093/humrep/dez119 31419301.

40. Market Velker BA, Denomme MM, Mann MR. Loss of genomic imprinting in mouse embryos with fast rates of preimplantation development in culture. Biol Reprod. 2012;86(5):143, 1–16. Epub 2012/01/27. doi: 10.1095/biolreprod.111.096602 22278980; PubMed Central PMCID: PMC4480067.

41. Song S, Ghosh J, Mainigi M, Turan N, Weinerman R, Truongcao M, et al. DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility. Clinical epigenetics. 2015;7(1):41. doi: 10.1186/s13148-015-0071-7 25901188

42. Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, et al. Association of four imprinting disorders and ART. Clinical epigenetics. 2019;11(1):21. Epub 2019/02/09. doi: 10.1186/s13148-019-0623-3 30732658; PubMed Central PMCID: PMC6367766.

43. Morbeck DE, Krisher RL, Herrick JR, Baumann NA, Matern D, Moyer T. Composition of commercial media used for human embryo culture. Fertil Steril. 2014;102(3):759–66 e9. Epub 2014/07/08. doi: 10.1016/j.fertnstert.2014.05.043 24998366.

44. Menezo Y, Clement P, Dale B. DNA Methylation Patterns in the Early Human Embryo and the Epigenetic/Imprinting Problems: A Plea for a More Careful Approach to Human Assisted Reproductive Technology (ART). International journal of molecular sciences. 2019;20(6). Epub 2019/03/20. doi: 10.3390/ijms20061342 30884872; PubMed Central PMCID: PMC6471582.

45. Dominguez F, Meseguer M, Aparicio-Ruiz B, Piqueras P, Quinonero A, Simon C. New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies. Fertil Steril. 2015;104(4):908–14. Epub 2015/07/22. doi: 10.1016/j.fertnstert.2015.06.032 26196234.

46. Stigliani S, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation. Human reproduction. 2013;28(10):2652–60. Epub 2013/07/28. doi: 10.1093/humrep/det314 23887072.

47. Simopoulou M, Sfakianoudis K, Antoniou N, Maziotis E, Rapani A, Bakas P, et al. Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle? Systems biology in reproductive medicine. 2018;64(5):305–23. Epub 2018/08/09. doi: 10.1080/19396368.2018.1504347 30088950.

48. Busnelli A, Dallagiovanna C, Reschini M, Paffoni A, Fedele L, Somigliana E. Risk factors for monozygotic twinning after in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2019;111(2):302–17. Epub 2019/01/30. doi: 10.1016/j.fertnstert.2018.10.025 30691632.

49. Fuchs F, Senat MV. Multiple gestations and preterm birth. Seminars in fetal & neonatal medicine. 2016;21(2):113–20. Epub 2016/01/23. doi: 10.1016/j.siny.2015.12.010 26795885.


Článok vyšiel v časopise

PLOS One


2019 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#