Research article Special Issues

Non-invasive analysis of bovine embryo metabolites during in vitro embryo culture using nuclear magnetic resonance

  • Received: 12 October 2016 Accepted: 02 December 2016 Published: 13 December 2016
  • The ability to identify embryos that have the highest developmental potential from a cohort would significantly increase the chances of achieving pregnancy. Metabolic analysis is a well-established analytical approach in biological systems. Starting from this idea, we chose to use high-resolution nuclear magnetic resonance (1H-NMR) spectroscopy. The aim of this study was to determine if it is possible to select viable embryos after 48 h of culture using metabolic activity as the parameter. We evaluated embryo metabolism after the first 48 h of culture and compared the activity of cleaved embryos that became blastocysts to cleaved embryos that did not develop to blastocysts, and in vitro fertilized (IVF) blastocysts and parthenogenetic-activated (PA) blastocysts. Our results show that citrate, pyruvate, myo-inositol and lysine have great impact on predicting embryo development. When we compared IVF and PA blastocysts, we found that acetate and phenylalanine concentrations are excellent parameters for evaluating blastocyst quality. Combining all these results, we were able to create a formula that predicts zygote development after 2 days of culture. In conclusion, we found that it is possible predict the future development of in vitro produced bovine embryos after only 2 days of culture using 1H-NMR.

    Citation: Marcello Rubessa, Andrea Ambrosi, Dianelys Gonzalez-Pena, Kathryn M. Polkoff, Scott E. Denmark, Matthew B. Wheeler. Non-invasive analysis of bovine embryo metabolites during in vitro embryo culture using nuclear magnetic resonance[J]. AIMS Bioengineering, 2016, 3(4): 538-551. doi: 10.3934/bioeng.2016.4.538

    Related Papers:

  • The ability to identify embryos that have the highest developmental potential from a cohort would significantly increase the chances of achieving pregnancy. Metabolic analysis is a well-established analytical approach in biological systems. Starting from this idea, we chose to use high-resolution nuclear magnetic resonance (1H-NMR) spectroscopy. The aim of this study was to determine if it is possible to select viable embryos after 48 h of culture using metabolic activity as the parameter. We evaluated embryo metabolism after the first 48 h of culture and compared the activity of cleaved embryos that became blastocysts to cleaved embryos that did not develop to blastocysts, and in vitro fertilized (IVF) blastocysts and parthenogenetic-activated (PA) blastocysts. Our results show that citrate, pyruvate, myo-inositol and lysine have great impact on predicting embryo development. When we compared IVF and PA blastocysts, we found that acetate and phenylalanine concentrations are excellent parameters for evaluating blastocyst quality. Combining all these results, we were able to create a formula that predicts zygote development after 2 days of culture. In conclusion, we found that it is possible predict the future development of in vitro produced bovine embryos after only 2 days of culture using 1H-NMR.


    加载中
    [1] Nyboe Andersen A, Goossens V, Bhattacharya S, et al. (2009) Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE: ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod 24: 1267–1287.
    [2] Graham J, Han T, Porter R, et al. (2000) Day 3 morphology is a poor predictor of blastocyst quality in extended culture. Fertil Steril 74: 495–497. doi: 10.1016/S0015-0282(00)00689-0
    [3] Guerif F, Le Gouge A, Giraudeau B, et al. (2007) Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: a prospective study based on 4042 embryos. Hum Reprod 22: 1973–1981. doi: 10.1093/humrep/dem100
    [4] Rijnders PM, Jansen CA (1998) The predictive value of day 3 embryo morphology regarding blastocyst formation, pregnancy and implantation rate after day 5 transfer following in-vitro fertilization or intracytoplasmic sperm injection. Hum Reprod 13: 2869–2873. doi: 10.1093/humrep/13.10.2869
    [5] Marhuenda-Egea FC, Martinez-Sabater E, Gonsalvez-Alvarez R, et al. (2010) A crucial step in assisted reproduction technology: human embryo selection using metabolomic evaluation. Fertil Steril 94: 772–774. doi: 10.1016/j.fertnstert.2009.10.013
    [6] Sakkas D, Gardner DK (2005) Noninvasive methods to assess embryo quality. Curr Opin Obstet Gynecol 17: 283–288. doi: 10.1097/01.gco.0000169106.69881.3e
    [7] Scott R, Seli E, Miller K, et al. (2008) Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study. Fertil Steril 90: 77–83. doi: 10.1016/j.fertnstert.2007.11.058
    [8] Seli E, Botros L, Sakkas D, et al. (2008) Noninvasive metabolomic profiling of embryo culture media using proton nuclear magnetic resonance correlates with reproductive potential of embryos in women undergoing in vitro fertilization. Fertil Steril 90: 2183–2189. doi: 10.1016/j.fertnstert.2008.07.1739
    [9] Vergouw CG, Botros LL, Roos P, et al. (2008) Metabolomic profiling by near–infrared spectroscopy as a tool to assess embryo viability: a novel, non-invasive method for embryo selection. Hum Reprod 23: 1499–1504. doi: 10.1093/humrep/den111
    [10] Rubessa M, Ambrosi A, Denmark SE, et al. (2016) Non-invasive analysis of gamete metabolites during in vitro embryo production using nuclear magnetic resonance. IJNTR 2: 54–58.
    [11] Katz-Jaffe MG, McReynolds S, Gardner DK, et al. (2009) The role of proteomics in defining the human embryonic secretome. Mol Hum Reprod 15: 271–277. doi: 10.1093/molehr/gap012
    [12] Lindon JC, Nicholson JK, Holmes E, et al. (2003) Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol Appl Pharm 187: 137–146. doi: 10.1016/S0041-008X(02)00079-0
    [13] Pauli GF, Jaki BU, Lankin DC (2005) Quantitative 1H NMR: development and potential of a method for natural products analysis. J Nat Prod 68: 133–149. doi: 10.1021/np0497301
    [14] Huang JYJ, Chung J-T, Tan SL, et al. (2007) High survival and hatching rates following vitrification of embryos at blastocyst stage: a bovine model study. Reprod Biomed Online 14: 464–470. doi: 10.1016/S1472-6483(10)60894-2
    [15] Ménézo YJR, Hérubel F (2002) Mouse and bovine models for human IVF*. Reprod Biomed Online 4: 170–175. doi: 10.1016/S1472-6483(10)61936-0
    [16] Parrish JJ, Susko-Parrish JL, Leibfried-Rutledge ML, et al. (1986) Bovine in vitro fertilization with frozen-thawed semen. Theriogenology 25: 591–600. doi: 10.1016/0093-691X(86)90143-3
    [17] Tervit HR, Whittingham DG, Rowson LE (1972) Successful culture in vitro of sheep and cattle ova. J Reprod Fertil 30: 493–497. doi: 10.1530/jrf.0.0300493
    [18] Sattar A, Rubessa M, Di Francesco S, et al. (2011) The influence of gamete co-incubation length on the In vitro fertility and sex ratio of bovine bulls with different penetration speed. Reprod Domest Anim 46: 1090–1097. doi: 10.1111/j.1439-0531.2011.01791.x
    [19] MacIntyre DA, Melguizo Sanchis D, Jimenez B, et al. (2011) Characterisation of human embryonic stem cells conditioning media by 1H-nuclear magnetic resonance spectroscopy. Plos One 6: e16732. doi: 10.1371/journal.pone.0016732
    [20] Nadal-Desbarats L, Veau S, Blasco H, et al. (2012) Is NMR metabolic profiling of spent embryo culture media useful to assist in vitro human embryo selection? Magma 26: 193–202.
    [21] Wallace M, Cottell E, Cullinane J, et al. (2014) (1)H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential. Syst Biol Reprod Med 60: 58–63. doi: 10.3109/19396368.2013.854426
    [22] Vajta G, Korosi T, Du Y, et al. (2008) The Well-of-the-Well system: an efficient approach to improve embryo development. Reprod Biomed Online 17: 73–81. doi: 10.1016/S1472-6483(10)60296-9
    [23] Van Royen E, Mangelschots K, De Neubourg D, et al. (1999) Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod 14: 2345–2349. doi: 10.1093/humrep/14.9.2345
    [24] Sturmey RG, Leese HJ (2003) Energy metabolism in pig oocytes and early embryos. Reproduction 126: 197–204. doi: 10.1530/rep.0.1260197
    [25] Houghton FD, Leese HJ (2004) Metabolism and developmental competence of the preimplantation embryo. Eur J Obstet Gynecol Reprod Biol 115 (Suppl 1): S92–S96.
    [26] Conaghan J, Hardy K, Handyside AH, et al. (1993) Selection criteria for human embryo transfer: a comparison of pyruvate uptake and morphology. J Assist Reprod Genet 10: 21–30. doi: 10.1007/BF01204436
    [27] Gardner DK, Lane M, Stevens J, et al. (2001) Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential. Fertil Steril 76: 1175–1180. doi: 10.1016/S0015-0282(01)02888-6
    [28] Brison DR, Houghton FD, Falconer D, et al. (2004) Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover. Hum Reprod 19: 2319–2324. doi: 10.1093/humrep/deh409
    [29] Houghton FD, Hawkhead JA, Humpherson PG, et al. (2002) Non-invasive amino acid turnover predicts human embryo developmental capacity. Hum Reprod 17: 999–1005. doi: 10.1093/humrep/17.4.999
    [30] Leese HJ (2002) Quiet please, do not disturb: a hypothesis of embryo metabolism and viability. Bioessays 24: 845–849. doi: 10.1002/bies.10137
    [31] Li X, Xu Y, Fu J, et al. (2015) Non-invasive metabolomic profiling of embryo culture media and morphology grading to predict implantation outcome in frozen-thawed embryo transfer cycles. J Assist Reprod Gen 32: 1597–1605. doi: 10.1007/s10815-015-0578-z
    [32] Seli E, Bruce C, Botros L, et al. (2011) Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome. J Assist Reprod Gen 28: 137–144. doi: 10.1007/s10815-010-9501-9
    [33] Seli E, Sakkas D, Scott R, et al. (2007) 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 88: 1350–1357. doi: 10.1016/j.fertnstert.2007.07.1390
    [34] Pudakalakatti SM, Uppangala S, D'Souza F, et al. (2013) NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential. Nmr Biomed 26: 20–27. doi: 10.1002/nbm.2814
    [35] Hardarson T, Ahlstrom A, Rogberg L, et al. (2012) Non-invasive metabolomic profiling of day 2 and 5 embryo culture medium: a prospective randomized trial. Hum Reprod 27: 89–96. doi: 10.1093/humrep/der373
    [36] Yadav BR, King WA, Betteridge KJ (1993) Relationships between the completion of first cleavage and the chromosomal complement, sex, and developmental rates of bovine embryos generated in vitro. Mol Reprod Dev 36: 434–439. doi: 10.1002/mrd.1080360405
    [37] Lonergan P, Khatir H, Piumi F, et al. (1999) Effect of time interval from insemination to first cleavage on the developmental characteristics, sex ratio and pregnancy rate after transfer of bovine embryos. J Reprod Fertil 117: 159–167. doi: 10.1530/jrf.0.1170159
    [38] Rubessa M, Boccia L, Campanile G, et al. (2011) Effect of energy source during culture on in vitro embryo development, resistance to cryopreservation and sex ratio. Theriogenology 76: 1347–1355. doi: 10.1016/j.theriogenology.2011.06.004
    [39] Holm P, Booth PJ, Schmidt MH, et al. (1999) High bovine blastocyst development in a static in vitro production system using SOFaa medium supplemented with sodium citrate and myo-inositol with or without serum-proteins. Theriogenology 52: 683–700. doi: 10.1016/S0093-691X(99)00162-4
    [40] Zhao Q, Yin T, Peng J, et al. (2013) Noninvasive metabolomic profiling of human embryo culture media using a simple spectroscopy adjunct to morphology for embryo assessment in in vitro fertilization (IVF). Int J Mol Sci 14: 6556–6570. doi: 10.3390/ijms14046556
  • Reader Comments
  • © 2016 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(4725) PDF downloads(1007) Cited by(2)

Article outline

Figures and Tables

Figures(5)  /  Tables(5)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog