DNA damage and metabolic activity in the preimplantation embryo

Sturmey, Roger G.; Hawkhead, Judith A.; Barker, E. Ann; Leese, Henry J.

doi:10.1093/humrep/den346

Cited by 101 publications

(73 citation statements)

References 82 publications

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“…Recent studies lend further evidence to this hypothesis as increased amino acid turnover has been positively correlated with DNA damage [Sturmey et al 2009] and cryopreserved human embryos that had the capacity to develop to the blastocyst stage upon subsequent thawing had a lower rate of amino acid turnover than those which arrested [Stokes et al 2007]. These studies demonstrated underlying metabolic differences between embryos of differing quality and thus provide the basis for the development of metabolic markers of viability for use in assisted reproductive technology.…”

Section: Introductionmentioning

confidence: 91%

¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

Wallace¹,

Cottell²,

Cullinane³

et al. 2013

Systems Biology in Reproductive Medicine

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Morphological assessment is currently the primary technique for selection of viable embryos for uterine transfer during assisted reproductive techniques, however this method has limited predictive power. The objective of this study was to employ NMR based metabolic profiling analysis of spent embryo culture media to identify novel biomarkers of embryo viability and provide insight into the metabolism of a viable embryo. A total of 37 patients undergoing IVF/ICSI treatment were recruited and 58 media samples were collected from embryos that were transferred back to the uterus. 1 H NMR spectra were acquired and analyzed resulting in the quantification of 12 metabolites in the media samples. Analysis of metabolite ratios revealed significant differences between those patients with positive (n ¼ 27) and negative (n ¼ 31) urinary bhCG results. Some of the most biologically relevant differences include a 17% increase in the formate to glycine ratio and a 22% decrease in the citrate to alanine ratio in the spent embryo media from the positive pregnancy group. Overall, the results indicate that metabolic profiling may provide a means of identifying biomarkers that aid selection of viable embryos.

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Section: Introductionmentioning

confidence: 91%

¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

Wallace¹,

Cottell²,

Cullinane³

et al. 2013

Systems Biology in Reproductive Medicine

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“…2d) indicated that oocytes under high oxygen environment had higher OXPHOS activity affecting the developmental rate. The 'Quiet Metabolism' theory proposed for embryo development under in vivo conditions is thought to be an adaptation of the embryos to reduce ROS production through aerobic respiration [34,35]. Reduced ROS level might help to reduce DNA damage and avoid aneuploidy that had been a major problem faced during human IVF [36,37].…”

Section: Discussionmentioning

confidence: 99%

Expression pattern of glucose metabolism genes correlate with development rate of buffalo oocytes and embryos in vitro under low oxygen condition

Kumar

Verma²,

Kumar³

et al. 2015

J Assist Reprod Genet

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Purpose This study evaluates the effect of low oxygen conditions (5 Vs 20 %) on buffalo embryo development. Expression patterns of key glucose metabolism genes (HK, PFK, LDH, PDH, G6PDH and Glut1) were assessed in buffalo oocytes and embryos cultured at 5 and 20 % oxygen and correlated with development rate. Methods Maturation rate was observed by determining MII stages by Aceto-orcein method and blastocyst formation was observed at 7 day post insemination (dpi). Expression levels of genes were determined by real time PCR in oocytes / embryos at 5 and 20 % O 2 .Results Oocyte maturation and blastocyst formation rates were significantly higher at 5 % O 2 as compared to 20 % O 2 (P<0.05). The expression pattern of glycolytic genes (HK, PFK and G6PDH) indicated that oocytes and embryos under 5 % O 2 tend to follow anaerobic glycolysis and pentose phosphate pathways to support optimum embryo development. Under 20 % O 2 , oocytes and embryos had high expression of PDH indicating higher oxidative phosphorylation. Further, less G6PDH expression at 20 % O 2 was indicative of lower pentose phosphate activity. Higher expression of LDH was observed in oocytes and embryos under 20 % O 2 indicating sub-optimal culture conditions. High Glut1 activity was observed in the oocytes / embryos at 5 % O 2 , indicative of high glucose uptake correlating with high expression of glycolytic genes. Conclusion The expression patterns of glucose metabolism genes could be a valuable indicator of the development potential of oocytes and embryos. The study indicates the importance of reduced oxygen conditions for production of good quality embryos.

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“…The comet assay was carried out as previously described [15,16] . Briefly, drug-treated cells were resuspended in 25 μL of PBS and mixed with 225 μL of low melting point agarose.…”

Section: Comet Assaysmentioning

confidence: 99%

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

Frame¹,

Noble²,

Klein³

et al. 2017

JCMT

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Aim:To develop new therapies for prostate cancer, disease heterogeneity must be addressed. This includes patient variation, multi-focal disease, cellular heterogeneity, genomic changes and epigenetic modification. This requires more representative models to be used in more innovative ways. Methods: This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue. Several assays were used; alamar blue, colony forming assays, γH2AX and Ki67 immunofluorescence and comet assays. Ptychographic quantitative phase imaging (QPI), a label-free imaging technique, combined with Cell Analysis Toolbox software, was implemented to carry out real-time analysis of cells and to retrieve morphological, kinetic and population data. Results: A combination of radiation and Vorinostat may be more effective than radiation alone. Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells. Analysis of QPI images showed that cell lines and primary cells differ in their size, motility and proliferation rate. A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture. Conclusion: Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity. Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

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DNA damage and metabolic activity in the preimplantation embryo

Cited by 101 publications

References 82 publications

¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

Expression pattern of glucose metabolism genes correlate with development rate of buffalo oocytes and embryos in vitro under low oxygen condition

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

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DNA damage and metabolic activity in the preimplantation embryo

Cited by 101 publications

References 82 publications

1H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

1H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

Expression pattern of glucose metabolism genes correlate with development rate of buffalo oocytes and embryos in vitro under low oxygen condition

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

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¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

¹H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential