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Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
REVIEW (Open Access)

Non-invasive assessment of oocyte developmental competence

Tiffany C. Y. Tan https://orcid.org/0000-0002-8290-688X A B C and Kylie R. Dunning https://orcid.org/0000-0002-0462-6479 A B C *
+ Author Affiliations
- Author Affiliations

A Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia.

B Australian Research Council Centre of Excellence for Nanoscale Biophotonics, The University of Adelaide, Adelaide, SA, Australia.

C Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, SA, Australia.

* Correspondence to: kylie.dunning@adelaide.edu.au

Reproduction, Fertility and Development 35(2) 39-50 https://doi.org/10.1071/RD22217
Published online: 18 October 2022

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Oocyte quality is a key factor influencing IVF success. The oocyte and surrounding cumulus cells, known collectively as the cumulus oocyte complex (COC), communicate bi-directionally and regulate each other’s metabolic function to support oocyte growth and maturation. Many studies have attempted to associate metabolic markers with oocyte quality, including metabolites in follicular fluid or ‘spent medium’ following maturation, gene expression of cumulus cells and measuring oxygen consumption in medium surrounding COCs. However, these methods fail to provide spatial metabolic information on the separate oocyte and cumulus cell compartments. Optical imaging of the autofluorescent cofactors – reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) – has been put forward as an approach to generate spatially resolved measurements of metabolism within individual cells of the COC. The optical redox ratio (FAD/[NAD(P)H + FAD]), calculated from these cofactors, can act as an indicator of overall metabolic activity in the oocyte and cumulus cell compartments. Confocal microscopy, fluorescence lifetime imaging microscopy (FLIM) and hyperspectral microscopy may be used for this purpose. This review provides an overview of current optical imaging techniques that capture the inner biochemistry within cells of the COC and discusses the potential for such imaging to assess oocyte developmental competence.

Keywords: autofluorescence, cellular metabolism, FAD, NAD(P)H, non-invasive, oocyte assessment, optical imaging, optical redox ratio.


References

Adashi, EY, and Gutman, R (2018). Delayed childbearing as a growing, previously unrecognized contributor to the national plural birth excess. Obstetrics & Gynecology 132, 999–1006.
Delayed childbearing as a growing, previously unrecognized contributor to the national plural birth excess.Crossref | GoogleScholarGoogle Scholar |

Ambekar, AS, Nirujogi, RS, Srikanth, SM, Chavan, S, Kelkar, DS, Hinduja, I, Zaveri, K, Prasad, TS, Harsha, HC, Pandey, A, and Mukherjee, S (2013). Proteomic analysis of human follicular fluid: a new perspective towards understanding folliculogenesis. Journal of Proteomics 87, 68–77.
Proteomic analysis of human follicular fluid: a new perspective towards understanding folliculogenesis.Crossref | GoogleScholarGoogle Scholar |

Anderson, E, and Albertini, DF (1976). Gap junctions between the oocyte and companion follicle cells in the mammalian ovary. Journal of Cell Biology 71, 680–686.
Gap junctions between the oocyte and companion follicle cells in the mammalian ovary.Crossref | GoogleScholarGoogle Scholar |

Andersson, H, Baechi, T, Hoechl, M, and Richter, C (1998). Autofluorescence of living cells. Journal of Microscopy 191, 1–7.
Autofluorescence of living cells.Crossref | GoogleScholarGoogle Scholar |

Bentov, Y, Yavorska, T, Esfandiari, N, Jurisicova, A, and Casper, RF (2011). The contribution of mitochondrial function to reproductive aging. Journal of Assisted Reproduction and Genetics 28, 773–783.
The contribution of mitochondrial function to reproductive aging.Crossref | GoogleScholarGoogle Scholar |

Bertoldo, MJ, Listijono, DR, Ho, W-HJ, Riepsamen, AH, Goss, DM, Richani, D, Jin, XL, Mahbub, S, Campbell, JM, Habibalahi, A, Loh, W-GN, Youngson, NA, Maniam, J, Wong, ASA, Selesniemi, K, Bustamante, S, Li, C, Zhao, Y, Marinova, MB, Kim, L-J, Lau, L, Wu, RM, Mikolaizak, AS, Araki, T, Le Couteur, DG, Turner, N, Morris, MJ, Walters, KA, Goldys, E, O’Neill, C, Gilchrist, RB, Sinclair, DA, Homer, HA, and Wu, LE (2020). NAD(+) repletion rescues female fertility during reproductive aging. Cell Reports 30, 1670–1681.e7.
NAD(+) repletion rescues female fertility during reproductive aging.Crossref | GoogleScholarGoogle Scholar |

Biggers, JD, Whittingham, DG, and Donahue, RP (1967). The pattern of energy metabolism in the mouse oöcyte and zygote. Proceedings of the National Academy of Sciences 58, 560–567.
The pattern of energy metabolism in the mouse oöcyte and zygote.Crossref | GoogleScholarGoogle Scholar |

Blacker, TS, and Duchen, MR (2016). Investigating mitochondrial redox state using NADH and NADPH autofluorescence. Free Radical Biology and Medicine 100, 53–65.
Investigating mitochondrial redox state using NADH and NADPH autofluorescence.Crossref | GoogleScholarGoogle Scholar |

Blacker, TS, Mann, ZF, Gale, JE, Ziegler, M, Bain, AJ, Szabadkai, G, and Duchen, MR (2014). Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nature Communications 5, 3936.
Separating NADH and NADPH fluorescence in live cells and tissues using FLIM.Crossref | GoogleScholarGoogle Scholar |

Bradley, J, Pope, I, Masia, F, Sanusi, R, Langbein, W, Swann, K, and Borri, P (2016). Quantitative imaging of lipids in live mouse oocytes and early embryos using CARS microscopy. Development 143, 2238–2247.
Quantitative imaging of lipids in live mouse oocytes and early embryos using CARS microscopy.Crossref | GoogleScholarGoogle Scholar |

Brison, DR, Sturmey, RG, and Leese, HJ (2014). Metabolic heterogeneity during preimplantation development: the missing link? Human Reproduction Update 20, 632–640.
Metabolic heterogeneity during preimplantation development: the missing link?Crossref | GoogleScholarGoogle Scholar |

Campugan, CA, Lim, M, Chow, DJX, Tan, TCY, Li, T, Saini, AA, Orth, A, Reineck, P, Schartner, EP, Thompson, JG, Dholakia, K, and Dunning, KR (2022). The effect of discrete wavelengths of visible light on the developing murine embryo. Journal of Assisted Reproduction and Genetics 39, 1825–1837.
The effect of discrete wavelengths of visible light on the developing murine embryo.Crossref | GoogleScholarGoogle Scholar |

Chambers, GM, Paul, RC, Harris, K, Fitzgerald, O, Boothroyd, CV, Rombauts, L, Chapman, MG, and Jorm, L (2017). Assisted reproductive technology in Australia and New Zealand: cumulative live birth rates as measures of success. Medical Journal of Australia 207, 114–118.
Assisted reproductive technology in Australia and New Zealand: cumulative live birth rates as measures of success.Crossref | GoogleScholarGoogle Scholar |

Chance, B (1952). Spectra and reaction kinetics of respiratory pigments of homogenized and intact cells. Nature 169, 215–221.
Spectra and reaction kinetics of respiratory pigments of homogenized and intact cells.Crossref | GoogleScholarGoogle Scholar |

Chance, B, and Thorell, B (1959). Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry. The Journal of Biological Chemistry 234, 3044–3050.
Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry.Crossref | GoogleScholarGoogle Scholar |

Chance, B, Cohen, P, Jobsis, F, and Schoener, B (1962a). Intracellular oxidation-reduction states in vivo. Science 137, 499–508.
Intracellular oxidation-reduction states in vivo.Crossref | GoogleScholarGoogle Scholar |

Chance, B, Cohen, P, Jobsis, F, and Schoener, B (1962b). Localized fluorometry of oxidation-reduction states of intracellular pyridine nucleotide in brain and kidney cortex of the anesthetized rat. Science 136, 325.
Localized fluorometry of oxidation-reduction states of intracellular pyridine nucleotide in brain and kidney cortex of the anesthetized rat.Crossref | GoogleScholarGoogle Scholar |

Chance, B, Estabrook, RW, and Ghosh, A (1964). Damped sinusoidal oscillations of cytoplasmic reduced pyridine nucleotide in yeast cells. Proceedings of the National Academy of Sciences 51, 1244–1251.
Damped sinusoidal oscillations of cytoplasmic reduced pyridine nucleotide in yeast cells.Crossref | GoogleScholarGoogle Scholar |

Chance, B, Schoener, B, Oshino, R, Itshak, F, and Nakase, Y (1979). Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. The Journal of Biological Chemistry 254, 4764–4771.
Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals.Crossref | GoogleScholarGoogle Scholar |

Cheng, E-H, Chen, S-U, Lee, T-H, Pai, Y-P, Huang, L-S, Huang, C-C, and Lee, M-S (2013). Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Human Reproduction 28, 929–936.
Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality.Crossref | GoogleScholarGoogle Scholar |

Cimadomo, D, Fabozzi, G, Vaiarelli, A, Ubaldi, N, Ubaldi, FM, and Rienzi, L (2018). Impact of maternal age on oocyte and embryo competence. Frontiers in Endocrinology 9, 327.
Impact of maternal age on oocyte and embryo competence.Crossref | GoogleScholarGoogle Scholar |

Cole, LW (2016). The evolution of per-cell organelle number. Frontiers in Cell and Developmental Biology 4, 85.
The evolution of per-cell organelle number.Crossref | GoogleScholarGoogle Scholar |

Croce, AC, and Bottiroli, G (2014). Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis. European Journal of Histochemistry 58, 2461.
Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis.Crossref | GoogleScholarGoogle Scholar |

Denisenko, V, Kuz’mina, TI, and Shokin, OV (2005). Dependence of Ca2+ release from intracellular stores on NADH and FAD levels in fertilized and unfertilized bovine oocytes. Tsitologiia 47, 704–708.

Drozdowicz-Tomsia, K, Anwer, AG, Cahill, MA, Madlum, KN, Maki, AM, Baker, MS, and Goldys, EM (2014). Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH ratio changes associated with metabolic inhibition. Journal of Biomedical Optics 19, 086016.
Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH ratio changes associated with metabolic inhibition.Crossref | GoogleScholarGoogle Scholar |

Dumesic, DA, Meldrum, DR, Katz-Jaffe, MG, Krisher, RL, and Schoolcraft, WB (2015). Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertility and Sterility 103, 303–316.
Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health.Crossref | GoogleScholarGoogle Scholar |

Dumollard, R, Marangos, P, Fitzharris, G, Swann, K, Duchen, M, and Carroll, J (2004). Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development 131, 3057–3067.
Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production.Crossref | GoogleScholarGoogle Scholar |

Dumollard, R, Ward, Z, Carroll, J, and Duchen, MR (2007). Regulation of redox metabolism in the mouse oocyte and embryo. Development 134, 455–465.
Regulation of redox metabolism in the mouse oocyte and embryo.Crossref | GoogleScholarGoogle Scholar |

Dumollard, R, Carroll, J, Duchen, MR, Campbell, K, and Swann, K (2009). Mitochondrial function and redox state in mammalian embryos. Seminars in Cell & Developmental Biology 20, 346–353.
Mitochondrial function and redox state in mammalian embryos.Crossref | GoogleScholarGoogle Scholar |

Dunning, KR, Cashman, K, Russell, DL, Thompson, JG, Norman, RJ, and Robker, RL (2010). Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biology of Reproduction 83, 909–918.
Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development.Crossref | GoogleScholarGoogle Scholar |

Dunning, KR, Akison, LK, Russell, DL, Norman, RJ, and Robker, RL (2011). Increased beta-oxidation and improved oocyte developmental competence in response to L-Carnitine during ovarian in vitro follicle development in mice. Biology of Reproduction 85, 548–555.
Increased beta-oxidation and improved oocyte developmental competence in response to L-Carnitine during ovarian in vitro follicle development in mice.Crossref | GoogleScholarGoogle Scholar |

Dunning, KR, Anastasi, MR, Zhang, VJ, Russell, DL, and Robker, RL (2014). Regulation of fatty acid oxidation in mouse cumulus-oocyte complexes during maturation and modulation by PPAR agonists. PLoS ONE 9, e87327.
Regulation of fatty acid oxidation in mouse cumulus-oocyte complexes during maturation and modulation by PPAR agonists.Crossref | GoogleScholarGoogle Scholar |

Ealy, AD, Wooldridge, LK, and McCoski, SR (2019). BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle. Journal of Animal Science 97, 2555–2568.
BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle.Crossref | GoogleScholarGoogle Scholar |

Ebner, T, Moser, M, Sommergruber, M, and Tews, G (2003). Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review. Human Reproduction Update 9, 251–262.
Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review.Crossref | GoogleScholarGoogle Scholar |

Eppig, JJ (2001). Oocyte control of ovarian follicular development and function in mammals. Reproduction 122, 829–838.
Oocyte control of ovarian follicular development and function in mammals.Crossref | GoogleScholarGoogle Scholar |

Erokhina, MV, Lepekha, LN, Voronezhskaya, EE, Nezlin, LP, Avdienko, VG, and Ergeshov, AE (2019). Application of laser scanning confocal microscopy for the visualization of M. tuberculosis in lung tissue samples with weak Ziehl-Neelsen staining. Journal of Clinical Medicine 8, 1185.
Application of laser scanning confocal microscopy for the visualization of M. tuberculosis in lung tissue samples with weak Ziehl-Neelsen staining.Crossref | GoogleScholarGoogle Scholar |

Feng, Y, Qi, J, Xue, X, Li, X, Liao, Y, Sun, Y, Tao, Y, Yin, H, Liu, W, Li, S, and Huang, R (2022). Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients. Reproduction 164, 1–8.
Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients.Crossref | GoogleScholarGoogle Scholar |

Ferguson, EM, and Leese, HJ (2006). A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development. Molecular Reproduction and Development 73, 1195–1201.
A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development.Crossref | GoogleScholarGoogle Scholar |

Fragouli, E, Wells, D, Iager, AE, Kayisli, UA, and Patrizio, P (2012). Alteration of gene expression in human cumulus cells as a potential indicator of oocyte aneuploidy. Human Reproduction 27, 2559–2568.
Alteration of gene expression in human cumulus cells as a potential indicator of oocyte aneuploidy.Crossref | GoogleScholarGoogle Scholar |

Fragouli, E, Spath, K, Alfarawati, S, Kaper, F, Craig, A, Michel, C-E, Kokocinski, F, Cohen, J, Munne, S, and Wells, D (2015). Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genetics 11, e1005241.
Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential.Crossref | GoogleScholarGoogle Scholar |

Ge, H, Tollner, TL, Hu, Z, Dai, M, Li, X, Guan, H, Shan, D, Zhang, X, Lv, J, Huang, C, and Dong, Q (2012). The importance of mitochondrial metabolic activity and mitochondrial DNA replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence. Molecular Reproduction and Development 79, 392–401.
The importance of mitochondrial metabolic activity and mitochondrial DNA replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence.Crossref | GoogleScholarGoogle Scholar |

Gebhardt, KM, Feil, DK, Dunning, KR, Lane, M, and Russell, DL (2011). Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertility and Sterility 96, 47–52.e2.
Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer.Crossref | GoogleScholarGoogle Scholar |

Georgakoudi, I, and Quinn, KP (2012). Optical imaging using endogenous contrast to assess metabolic state. Annual Review of Biomedical Engineering 14, 351–367.
Optical imaging using endogenous contrast to assess metabolic state.Crossref | GoogleScholarGoogle Scholar |

Gilchrist, RB, Lane, M, and Thompson, JG (2008). Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Human Reproduction Update 14, 159–177.
Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality.Crossref | GoogleScholarGoogle Scholar |

Gosnell, ME, Anwer, AG, Mahbub, SB, Menon Perinchery, S, Inglis, DW, Adhikary, PP, Jazayeri, JA, Cahill, MA, Saad, S, Pollock, CA, Sutton-McDowall, ML, Thompson, JG, and Goldys, EM (2016a). Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features. Scientific Reports 6, 23453.
Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features.Crossref | GoogleScholarGoogle Scholar |

Gosnell, ME, Anwer, AG, Cassano, JC, Sue, CM, and Goldys, EM (2016b). Functional hyperspectral imaging captures subtle details of cell metabolism in olfactory neurosphere cells, disease-specific models of neurodegenerative disorders. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1863, 56–63.
Functional hyperspectral imaging captures subtle details of cell metabolism in olfactory neurosphere cells, disease-specific models of neurodegenerative disorders.Crossref | GoogleScholarGoogle Scholar |

Gutnisky, C, Dalvit, GC, Thompson, JG, and Cetica, PD (2014). Pentose phosphate pathway activity: effect on in vitro maturation and oxidative status of bovine oocytes. Reproduction, Fertility and Development 26, 931–942.
Pentose phosphate pathway activity: effect on in vitro maturation and oxidative status of bovine oocytes.Crossref | GoogleScholarGoogle Scholar |

Habibalahi, A, Bala, C, Allende, A, Anwer, AG, and Goldys, EM (2019). Novel automated non invasive detection of ocular surface squamous neoplasia using multispectral autofluorescence imaging. The Ocular Surface 17, 540–550.
Novel automated non invasive detection of ocular surface squamous neoplasia using multispectral autofluorescence imaging.Crossref | GoogleScholarGoogle Scholar |

Hemmings, KE, Leese, HJ, and Picton, HM (2012). Amino acid turnover by bovine oocytes provides an index of oocyte developmental competence in vitro. Biology of Reproduction 165, 1–12.
Amino acid turnover by bovine oocytes provides an index of oocyte developmental competence in vitro.Crossref | GoogleScholarGoogle Scholar |

Heppert, JK, Dickinson, DJ, Pani, AM, Higgins, CD, Steward, A, Ahringer, J, Kuhn, JR, and Goldstein, B (2016). Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system. Molecular Biology of the Cell 27, 3385–3394.
Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system.Crossref | GoogleScholarGoogle Scholar |

Hirata, S, Hoshi, K, Shoda, T, and Mabuchi, T (2002). Spermatozoon and mitochondrial DNA. Reproductive Medicine and Biology 1, 41–47.
Spermatozoon and mitochondrial DNA.Crossref | GoogleScholarGoogle Scholar |

Ji, S, Chance, B, Nishiki, K, Smith, T, and Rich, T (1979). Micro-light guides: a new method for measuring tissue fluorescence and reflectance. American Journal of Physiology - Cell Physiology 236, C144–C156.
Micro-light guides: a new method for measuring tissue fluorescence and reflectance.Crossref | GoogleScholarGoogle Scholar |

Johnson ID (2010) ‘Molecular probes handbook: a guide to fluorescent probes and labeling technologies.’ (Life Technologies Corporation)

Johnson, JA, Tough, S, and Sogc Genetics, C (2012). Delayed child-bearing. Journal of Obstetrics and Gynaecology Canada 34, 80–93.
Delayed child-bearing.Crossref | GoogleScholarGoogle Scholar |

Jungheim, ES, Macones, GA, Odem, RR, Patterson, BW, Lanzendorf, SE, Ratts, VS, and Moley, KH (2011). Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertility and Sterility 95, 1970–1974.
Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.Crossref | GoogleScholarGoogle Scholar |

Kolenc, OI, and Quinn, KP (2019). Evaluating cell metabolism through autofluorescence imaging of NAD(P)H and FAD. Antioxidants & Redox Signaling 30, 875–889.
Evaluating cell metabolism through autofluorescence imaging of NAD(P)H and FAD.Crossref | GoogleScholarGoogle Scholar |

Krisher, RL (2018). Maternal age affects oocyte developmental potential at both ends of the age spectrum. Reproduction, Fertility and Development 31, 1–9.
Maternal age affects oocyte developmental potential at both ends of the age spectrum.Crossref | GoogleScholarGoogle Scholar |

Kunz, WS, and Kunz, W (1985). Contribution of different enzymes to flavoprotein fluorescence of isolated rat liver mitochondria. Biochimica et Biophysica Acta (BBA) - General Subjects 841, 237–246.
Contribution of different enzymes to flavoprotein fluorescence of isolated rat liver mitochondria.Crossref | GoogleScholarGoogle Scholar |

Lasienë, K, Vitkus, A, Valanèiûtë, A, and Lasys, V (2009). Morphological criteria of oocyte quality. Medicina 45, 509.
Morphological criteria of oocyte quality.Crossref | GoogleScholarGoogle Scholar |

Lee, JH, Park, JK, Yoon, SY, Park, EA, Jun, JH, Lim, HJ, Kim, J, and Song, H (2021). Advanced maternal age deteriorates the developmental competence of vitrified oocytes in mice. Cells 10, 1563.
Advanced maternal age deteriorates the developmental competence of vitrified oocytes in mice.Crossref | GoogleScholarGoogle Scholar |

Liberti, MV, and Locasale, JW (2016). The Warburg effect: how does it benefit cancer cells? Trends in Biochemical Sciences 41, 211–218.
The Warburg effect: how does it benefit cancer cells?Crossref | GoogleScholarGoogle Scholar |

Mahbub, SB, Guller, A, Campbell, JM, Anwer, AG, Gosnell, ME, Vesey, G, and Goldys, EM (2019). Non-invasive monitoring of functional state of articular cartilage tissue with label-free unsupervised hyperspectral imaging. Scientific Reports 9, 4398.
Non-invasive monitoring of functional state of articular cartilage tissue with label-free unsupervised hyperspectral imaging.Crossref | GoogleScholarGoogle Scholar |

Mahbub, SB, Nguyen, LT, Habibalahi, A, Campbell, JM, Anwer, AG, Qadri, UM, Gill, A, Chou, A, Wong, MG, Gosnell, ME, Pollock, CA, Saad, S, and Goldys, EM (2021). Non-invasive assessment of exfoliated kidney cells extracted from urine using multispectral autofluorescence features. Scientific Reports 11, 10655.
Non-invasive assessment of exfoliated kidney cells extracted from urine using multispectral autofluorescence features.Crossref | GoogleScholarGoogle Scholar |

Masters, BR, Kriete, A, and Kukulies, J (1993). Ultraviolet confocal fluorescence microscopy of the in vitro cornea: redox metabolic imaging. Applied Optics 32, 592–596.
Ultraviolet confocal fluorescence microscopy of the in vitro cornea: redox metabolic imaging.Crossref | GoogleScholarGoogle Scholar |

May-Panloup, P, Chrétien, MF, Jacques, C, Vasseur, C, Malthièry, Y, and Reynier, P (2005). Low oocyte mitochondrial DNA content in ovarian insufficiency. Human Reproduction 20, 593–597.
Low oocyte mitochondrial DNA content in ovarian insufficiency.Crossref | GoogleScholarGoogle Scholar |

May-Panloup, P, Boguenet, M, El Hachem, H, Bouet, P-E, and Reynier, P (2021). Embryo and its mitochondria. Antioxidants 10, 139.
Embryo and its mitochondria.Crossref | GoogleScholarGoogle Scholar |

McKenzie, LJ, Pangas, SA, Carson, SA, Kovanci, E, Cisneros, P, Buster, JE, Amato, P, and Matzuk, MM (2004). Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Human Reproduction 19, 2869–2874.
Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF.Crossref | GoogleScholarGoogle Scholar |

McLennan, HJ, Saini, A, Dunning, KR, and Thompson, JG (2020). Oocyte and embryo evaluation by AI and multi-spectral auto-fluorescence imaging: livestock embryology needs to catch-up to clinical practice. Theriogenology 150, 255–262.
Oocyte and embryo evaluation by AI and multi-spectral auto-fluorescence imaging: livestock embryology needs to catch-up to clinical practice.Crossref | GoogleScholarGoogle Scholar |

Mendoza, C, Ruiz-Requena, E, Ortega, E, Cremades, N, Martinez, F, Bernabeu, R, Greco, E, and Tesarik, J (2002). Follicular fluid markers of oocyte developmental potential. Human Reproduction 17, 1017–1022.
Follicular fluid markers of oocyte developmental potential.Crossref | GoogleScholarGoogle Scholar |

Nohales-Córcoles, M, Sevillano-Almerich, G, Di Emidio, G, Tatone, C, Cobo, AC, Dumollard, R, and De los Santos Molina, MJ (2016). Impact of vitrification on the mitochondrial activity and redox homeostasis of human oocyte. Human Reproduction 31, 1850–1858.
Impact of vitrification on the mitochondrial activity and redox homeostasis of human oocyte.Crossref | GoogleScholarGoogle Scholar |

Ntostis, P, Iles, D, Kokkali, G, Vaxevanoglou, T, Kanavakis, E, Pantou, A, Huntriss, J, Pantos, K, and Picton, HM (2022). The impact of maternal age on gene expression during the GV to MII transition in euploid human oocytes. Human Reproduction 37, 80–92.
The impact of maternal age on gene expression during the GV to MII transition in euploid human oocytes.Crossref | GoogleScholarGoogle Scholar |

O’Brien, JK, Dwarte, D, Ryan, JP, Maxwell, WM, and Evans, G (1996). Developmental capacity, energy metabolism and ultrastructure of mature oocytes from prepubertal and adult sheep. Reproduction, Fertility and Development 8, 1029–1037.
Developmental capacity, energy metabolism and ultrastructure of mature oocytes from prepubertal and adult sheep.Crossref | GoogleScholarGoogle Scholar |

O’Gorman, A, Wallace, M, Cottell, E, Gibney, MJ, McAuliffe, FM, Wingfield, M, and Brennan, L (2013). Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence. Reproduction 146, 389–395.
Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar |

Osellame, LD, Blacker, TS, and Duchen, MR (2012). Cellular and molecular mechanisms of mitochondrial function. Best Practice & Research Clinical Endocrinology & Metabolism 26, 711–723.
Cellular and molecular mechanisms of mitochondrial function.Crossref | GoogleScholarGoogle Scholar |

Ozturk, S, Sozen, B, and Demir, N (2014). Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species. Molecular Human Reproduction 20, 15–30.
Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species.Crossref | GoogleScholarGoogle Scholar |

Perevedentseva, E, Krivokharchenko, A, Karmenyan, AV, Chang, H-H, and Cheng, C-L (2019). Raman spectroscopy on live mouse early embryo while it continues to develop into blastocyst in vitro. Scientific Reports 9, 6636.
Raman spectroscopy on live mouse early embryo while it continues to develop into blastocyst in vitro.Crossref | GoogleScholarGoogle Scholar |

Pontes, JHF, Nonato-Junior, I, Sanches, BV, Ereno-Junior, JC, Uvo, S, Barreiros, TRR, Oliveira, JA, Hasler, JF, and Seneda, MM (2009). Comparison of embryo yield and pregnancy rate between in vivo and in vitro methods in the same Nelore (Bos indicus) donor cows. Theriogenology 71, 690–697.
Comparison of embryo yield and pregnancy rate between in vivo and in vitro methods in the same Nelore (Bos indicus) donor cows.Crossref | GoogleScholarGoogle Scholar |

Preis, KA, Seidel, G, and Gardner, DK (2005). Metabolic markers of developmental competence for in vitro-matured mouse oocytes. Reproduction 130, 475–483.
Metabolic markers of developmental competence for in vitro-matured mouse oocytes.Crossref | GoogleScholarGoogle Scholar |

Quinn, KP, Sridharan, GV, Hayden, RS, Kaplan, DL, Lee, K, and Georgakoudi, I (2013). Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Scientific Reports 3, 3432.
Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation.Crossref | GoogleScholarGoogle Scholar |

Quistorff B, Chance B (1986) Redox scanning in the study of metabolic zonation of liver. In ‘Regulation of hepatic metabolism: intra- and intercellular compartmentation’. (Eds RG Thurman, FC Kauffman, K Jungermann) pp. 185–207. (Springer US: Boston, MA)

Quistorff, B, Haselgrove, JC, and Chance, B (1985). High spatial resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument. Analytical Biochemistry 148, 389–400.
High spatial resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument.Crossref | GoogleScholarGoogle Scholar |

Richani, D, Dunning, KR, Thompson, JG, and Gilchrist, RB (2021). Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence. Human Reproduction Update 27, 27–47.
Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar |

Roshchina, VV (2012). Vital autofluorescence: application to the study of plant living cells. International Journal of Spectroscopy 2012, 124672.
Vital autofluorescence: application to the study of plant living cells.Crossref | GoogleScholarGoogle Scholar |

Sanchez, T, Wang, T, Pedro, MV, Zhang, M, Esencan, E, Sakkas, D, Needleman, D, and Seli, E (2018). Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes. Fertility and Sterility 110, 1387–1397.
Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes.Crossref | GoogleScholarGoogle Scholar |

Sanchez, T, Venturas, M, Aghvami, SA, Yang, X, Fraden, S, Sakkas, D, and Needleman, DJ (2019). Combined noninvasive metabolic and spindle imaging as potential tools for embryo and oocyte assessment. Human Reproduction 34, 2349–2361.
Combined noninvasive metabolic and spindle imaging as potential tools for embryo and oocyte assessment.Crossref | GoogleScholarGoogle Scholar |

Santos, TA, El Shourbagy, S, and St. John, JC (2006). Mitochondrial content reflects oocyte variability and fertilization outcome. Fertility and Sterility 85, 584–591.
Mitochondrial content reflects oocyte variability and fertilization outcome.Crossref | GoogleScholarGoogle Scholar |

Santos Monteiro, CA, Chow, DJX, Leal, GR, Tan, TCY, Reis Ferreira, AM, Thompson, JG, and Dunning, KR (2021). Optical imaging of cleavage stage bovine embryos using hyperspectral and confocal approaches reveals metabolic differences between on-time and fast-developing embryos. Theriogenology 159, 60–68.
Optical imaging of cleavage stage bovine embryos using hyperspectral and confocal approaches reveals metabolic differences between on-time and fast-developing embryos.Crossref | GoogleScholarGoogle Scholar |

Scholz, R, Thurman, RG, Williamson, JR, Chance, B, and Bücher, T (1969). Flavin and pyridine nucleotide oxidation-reduction changes in perfused rat liver. I. Anoxia and subcellular localization of fluorescent flavoproteins. The Journal of Biological Chemistry 244, 2317–2324.
Flavin and pyridine nucleotide oxidation-reduction changes in perfused rat liver. I. Anoxia and subcellular localization of fluorescent flavoproteins.Crossref | GoogleScholarGoogle Scholar |

Scott, R, Seli, E, Miller, K, Sakkas, D, Scott, K, and Burns, DH (2008). Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study. Fertility and Sterility 90, 77–83.
Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study.Crossref | GoogleScholarGoogle Scholar |

Seli, E, Sakkas, D, Scott, R, Kwok, SC, Rosendahl, SM, and Burns, DH (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. Fertility and Sterility 88, 1350–1357.
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.Crossref | GoogleScholarGoogle Scholar |

Shen, X, Liu, X, Zhu, P, Zhang, Y, Wang, J, Wang, Y, Wang, W, Liu, J, Li, N, and Liu, F (2017). Proteomic analysis of human follicular fluid associated with successful in vitro fertilization. Reproductive Biology and Endocrinology 15, 58.
Proteomic analysis of human follicular fluid associated with successful in vitro fertilization.Crossref | GoogleScholarGoogle Scholar |

Skala M, Ramanujam N (2010) Multiphoton redox ratio imaging for metabolic monitoring in vivo. In ‘Advanced protocols in oxidative stress II. Vol. 594’. (Ed. D Armstrong) pp. 155–162. Methods in molecular biology. (Humana Press: Totowa, NJ). 10.1007/978-1-60761-411-1_11

Staikopoulos V, Gosnell ME, Anwer AG, Mustafa S, Hutchinson MR, Goldys EM (2016) Hyperspectral imaging of endogenous fluorescent metabolic molecules to identify pain states in central nervous system tissue. In ‘SPIE BioPhotonics Australasia’. p. 8. (SPIE)

Sturmey, RG, O’Toole, PJ, and Leese, HJ (2006). Fluorescence resonance energy transfer analysis of mitochondrial:lipid association in the porcine oocyte. Reproduction 132, 829–837.
Fluorescence resonance energy transfer analysis of mitochondrial:lipid association in the porcine oocyte.Crossref | GoogleScholarGoogle Scholar |

Sugiura, K, Su, Y-Q, Diaz, FJ, Pangas, SA, Sharma, S, Wigglesworth, K, O’Brien, MJ, Matzuk, MM, Shimasaki, S, and Eppig, JJ (2007). Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134, 2593–2603.
Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells.Crossref | GoogleScholarGoogle Scholar |

Sutton-McDowall, ML, Gilchrist, RB, and Thompson, JG (2010). The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction 139, 685–695.
The pivotal role of glucose metabolism in determining oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar |

Sutton-McDowall, ML, Mottershead, DG, Gardner, DK, Gilchrist, RB, and Thompson, JG (2012). Metabolic differences in bovine cumulus-oocyte complexes matured in vitro in the presence or absence of follicle-stimulating hormone and bone morphogenetic protein 15. Biology of Reproduction 87, 1–8.
Metabolic differences in bovine cumulus-oocyte complexes matured in vitro in the presence or absence of follicle-stimulating hormone and bone morphogenetic protein 15.Crossref | GoogleScholarGoogle Scholar |

Sutton-McDowall, ML, Purdey, M, Brown, HM, Abell, AD, Mottershead, DG, Cetica, PD, Dalvit, GC, Goldys, EM, Gilchrist, RB, Gardner, DK, and Thompson, JG (2015). Redox and anti-oxidant state within cattle oocytes following in vitro maturation with bone morphogenetic protein 15 and follicle stimulating hormone. Molecular Reproduction and Development 82, 281–294.
Redox and anti-oxidant state within cattle oocytes following in vitro maturation with bone morphogenetic protein 15 and follicle stimulating hormone.Crossref | GoogleScholarGoogle Scholar |

Sutton-McDowall, ML, Wu, LLY, Purdey, M, Abell, AD, Goldys, EM, MacMillan, KL, Thompson, JG, and Robker, RL (2016). Nonesterified fatty acid-induced endoplasmic reticulum stress in cattle cumulus oocyte complexes alters cell metabolism and developmental competence. Biology of Reproduction 94, 23.
Nonesterified fatty acid-induced endoplasmic reticulum stress in cattle cumulus oocyte complexes alters cell metabolism and developmental competence.Crossref | GoogleScholarGoogle Scholar |

Sutton-McDowall, ML, Gosnell, M, Anwer, AG, White, M, Purdey, M, Abell, AD, Goldys, EM, and Thompson, JG (2017). Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%). Human Reproduction 32, 2016–2025.
Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%).Crossref | GoogleScholarGoogle Scholar |

Swoger, J, Pampaloni, F, and Stelzer, EHK (2014). Light-sheet-based fluorescence microscopy for three-dimensional imaging of biological samples. Cold Spring Harbor Protocols 2014, 1–8.
Light-sheet-based fluorescence microscopy for three-dimensional imaging of biological samples.Crossref | GoogleScholarGoogle Scholar |

Takenaka, M, Horiuchi, T, and Yanagimachi, R (2007). Effects of light on development of mammalian zygotes. Proceedings of the National Academy of Sciences 104, 14289–14293.
Effects of light on development of mammalian zygotes.Crossref | GoogleScholarGoogle Scholar |

Tan, TCY, Brown, HM, Thompson, JG, Mustafa, S, and Dunning, KR (2022a). Optical imaging detects metabolic signatures associated with oocyte quality. Biology of Reproduction , ioac145.
Optical imaging detects metabolic signatures associated with oocyte quality.Crossref | GoogleScholarGoogle Scholar |

Tan, TCY, Mahbub, SB, Campbell, JM, Habibalahi, A, Campugan, CA, Rose, RD, Chow, DJX, Mustafa, S, Goldys, EM, and Dunning, KR (2022b). Non-invasive, label-free optical analysis to detect aneuploidy within the inner cell mass of the preimplantation embryo. Human Reproduction 37, 14–29.
Non-invasive, label-free optical analysis to detect aneuploidy within the inner cell mass of the preimplantation embryo.Crossref | GoogleScholarGoogle Scholar |

Valsangkar, D, and Downs, SM (2013). A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes. Biology of Reproduction 89, 43.
A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes.Crossref | GoogleScholarGoogle Scholar |

van der Reest, J, Nardini Cecchino, G, Haigis, MC, and Kordowitzki, P (2021). Mitochondria: their relevance during oocyte ageing. Ageing Research Reviews 70, 101378.
Mitochondria: their relevance during oocyte ageing.Crossref | GoogleScholarGoogle Scholar |

Wai, T, Ao, A, Zhang, X, Cyr, D, Dufort, D, and Shoubridge, EA (2010). The role of mitochondrial DNA copy number in mammalian fertility. Biology of Reproduction 83, 52–62.
The role of mitochondrial DNA copy number in mammalian fertility.Crossref | GoogleScholarGoogle Scholar |

Wang, Q, and Sun, Q-Y (2007). Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reproduction, Fertility and Development 19, 1–12.
Evaluation of oocyte quality: morphological, cellular and molecular predictors.Crossref | GoogleScholarGoogle Scholar |

Windom BC, Hahn DW (2013) Raman spectroscopy. In ‘Encyclopedia of tribology’. (Eds QJ Wang, Y-W Chung) pp. 2742–2747. (Springer US: Boston, MA)

Wrenzycki, C (2021). Parameters to identify good quality oocytes and embryos in cattle. Reproduction, Fertility and Development 34, 190–202.
Parameters to identify good quality oocytes and embryos in cattle.Crossref | GoogleScholarGoogle Scholar |

Wu, Y-T, Tang, L, Cai, J, Lu, X-E, Xu, J, Zhu, X-M, Luo, Q, and Huang, H-F (2007). High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Human Reproduction 22, 1526–1531.
High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development.Crossref | GoogleScholarGoogle Scholar |

Yakubovskaya, E, Zaliznyak, T, Martínez Martínez, J, and Taylor, GT (2019). Tear down the fluorescent curtain: a new fluorescence suppression method for raman microspectroscopic analyses. Scientific Reports 9, 15785.
Tear down the fluorescent curtain: a new fluorescence suppression method for raman microspectroscopic analyses.Crossref | GoogleScholarGoogle Scholar |

Yeo, CX, Gilchrist, RB, and Lane, M (2009). Disruption of bidirectional oocyte-cumulus paracrine signaling during in vitro maturation reduces subsequent mouse oocyte developmental competence. Biology of Reproduction 80, 1072–1080.
Disruption of bidirectional oocyte-cumulus paracrine signaling during in vitro maturation reduces subsequent mouse oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar |