Non-destructive monitoring of mouse embryo development and its qualitative evaluation at the molecular level using Raman spectroscopy

Current research focuses on embryonic development and quality not only by considering fundamental biology, but also by aiming to improve assisted reproduction technologies, such as in vitro fertilization. In this study, we explored the development of mouse embryo and its quality based on molecular information, obtained nondestructively using Raman spectroscopy. The detailed analysis of Raman spectra measured in situ during embryonic development revealed a temporary increase in protein content after fertilization. Proteins with a β-sheet structure—present in the early stages of embryonic development—are derived from maternal oocytes, while α-helical proteins are additionally generated by switching on a gene after fertilization. The transition from maternal to embryonic control during development can be non-destructively profiled, thus facilitating the in situ assessment of structural changes and component variation in proteins generated by metabolic activity. Furthermore, it was indicated that embryos with low-grade morphology had high concentrations of lipids and hydroxyapatite. This technique could be used for embryo quality testing in the future.

[1]  D. De Neubourg,et al.  Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. , 1999, Human Reproduction.

[2]  K. M. Kim.  Apoptosis and calcification. , 1995, Scanning microscopy.

[3]  G. Schultz,et al.  Changes in the quantity of histone and actin messenger RNA during the development of preimplantation mouse embryos. , 1983, Developmental biology.

[4]  Y. Ozaki,et al.  Medical Application of Raman Spectroscopy , 1988 .

[5]  T. Shimanouchi,et al.  Interpretation of the doublet at 850 and 830 cm-1 in the Raman spectra of tyrosyl residues in proteins and certain model compounds. , 1975, Biochemistry.

[6]  M. Katsuki,et al.  Simple and efficient vitrification procedure for cryopreservation of mouse embryos. , 1997, Experimental animals.

[7]  J. Garrels,et al.  Quantitative analysis of protein synthesis in mouse embryos. I. Extensive reprogramming at the one- and two-cell stages. , 1991, Development.

[8]  Alistair Elfick,et al.  The changing biochemical composition and organisation of the murine oocyte and early embryo as revealed by Raman spectroscopic mapping , 2012 .

[9]  A. Handyside,et al.  Selection criteria for human embryo transfer: A comparison of pyruvate uptake and morphology , 2005, Journal of Assisted Reproduction and Genetics.

[10]  P. Haggarty,et al.  Fatty acid metabolism in human preimplantation embryos. , 2006, Human reproduction.

[11]  N. Spears,et al.  Raman Micro-Spectroscopy Can Be Used to Investigate the Developmental Stage of the Mouse Oocyte , 2013, PloS one.

[12]  G. D. De Meyer,et al.  Biotin- or digoxigenin-conjugated nucleotides bind to matrix vesicles in atherosclerotic plaques. , 1996, The American journal of pathology.

[13]  Andreas Ritter,et al.  Manipulating The Mouse Embryo A Laboratory Manual , 2016 .

[14]  D. Gardner,et al.  Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential. , 2000, Fertility and sterility.

[15]  Ioan Notingher,et al.  In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro. , 2004, Analytical chemistry.

[16]  V. Lehto,et al.  Parietal and visceral endoderm differ in their expression of intermediate filaments. , 1983, The EMBO journal.

[17]  H. Barr,et al.  Raman spectroscopy for identification of epithelial cancers. , 2004, Faraday discussions.

[18]  G. Schatten,et al.  Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[19]  M. Piccinini,et al.  Raman spectroscopy-based approach to detect aging-related oxidative damage in the mouse oocyte , 2013, Journal of Assisted Reproduction and Genetics.

[20]  G. Kidder.  The genetic program for preimplantation development. , 1992, Developmental genetics.

[21]  P. C. Steptoe,et al.  BIRTH AFTER THE REIMPLANTATION OF A HUMAN EMBRYO , 1978, The Lancet.

[22]  J. Shaw,et al.  A formula for scoring human embryo growth rates in in vitro fertilization: Its value in predicting pregnancy and in comparison with visual estimates of embryo quality , 1986, Journal of in Vitro Fertilization and Embryo Transfer.

[23]  Kylie R. Dunning,et al.  Beta-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development1 , 2010, Biology of reproduction.

[24]  Alexander Jesacher,et al.  Characterisation of the dynamic behaviour of lipid droplets in the early mouse embryo using adaptive harmonic generation microscopy , 2010, BMC Cell Biology.

[25]  L A Scott,et al.  The successful use of pronuclear embryo transfers the day following oocyte retrieval. , 1998, Human reproduction.

[26]  L. Schurgers,et al.  Dialysis Accelerates Medial Vascular Calcification in Part by Triggering Smooth Muscle Cell Apoptosis , 2008, Circulation.

[27]  Paul R. Carey,et al.  Biochemical Applications of Raman and Resonance Raman Spectroscopies , 1982 .

[28]  D. Gardner,et al.  Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. , 2000, Fertility and sterility.

[29]  Denny Sakkas,et al.  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. , 2007, Fertility and sterility.

[30]  A. Talari,et al.  Raman Spectroscopy of Biological Tissues , 2007 .

[31]  R. Schultz.  Experimental approaches to mammalian embryonic development: Molecular aspects of mammalian oocyte growth and maturation , 1987 .

[32]  Kim Km.  Apoptosis and calcification. , 1995 .

[33]  Auner Aw,et al.  Double-Stranded DNA Damage Assessed with Raman Spectroscopy , 2016 .

[34]  M. Rao,et al.  Impact of embryonic expression of enhanced green fluorescent protein on early mouse development. , 2004, Biochemical and biophysical research communications.

[35]  Toshitaka Horiuchi,et al.  Effects of light on development of mammalian zygotes , 2007, Proceedings of the National Academy of Sciences.

[36]  H. Barr,et al.  Medical applications of Raman spectroscopy: from proof of principle to clinical implementation. , 2002, Biopolymers.

[37]  J. Skepper,et al.  Apoptosis Regulates Human Vascular Calcification In Vitro: Evidence for Initiation of Vascular Calcification by Apoptotic Bodies , 2000, Circulation research.

[38]  D. De Neubourg,et al.  Characterization of a top quality embryo, a step towards single-embryo transfer. , 1999, Human reproduction.

[39]  S. Pickering,et al.  Changes in actin distribution during fertilization of the mouse egg. , 1984, Journal of embryology and experimental morphology.

[40]  Yukihiro Ozaki,et al.  Near‐infrared Fourier transform Raman spectroscopic study of human brain tissues and tumours , 1994 .

[41]  Max Diem,et al.  Shedding new light on the molecular architecture of oocytes using a combination of synchrotron Fourier transform-infrared and Raman spectroscopic mapping. , 2008, Analytical chemistry.

[42]  M. Morgan,et al.  Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines , 2001, Molecular carcinogenesis.