Viñals Gonzalez, Xavier;
(2024)
The efficiency of modulation contrast microscopy image
analysis as a predictive tool for human oocyte quality.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Human oocyte quality is currently described based on the observed ability to recognise the sperm cell, develop into an embryo and establish a pregnancy. When observed under the microscope, differences in oocytes can be observed (ie. cytoplasmic granulation, vacuoles, smooth endoplasmic reticulum), although these have not been strongly associated with the cells’ quality. Currently, there are no metrics to depict small changes in the ooplasm, which could provide information on the potential of the cell. Image analysis of over a thousand and three hundred oocytes was conducted in the course of this study, where images were turned into quantifiable data. This data was used to explore different aspects of the female gamete namely physical (maturation stage), molecular (protein content, mitochondrial DNA copy number and messenger RNA) and temporal (in vitro maturation). A novel imaging comprehensive algorithm of reproductive efficiency (i-CARE) was designed with known outcome data (up to clinical pregnancy), to define oocyte quality based on a single oocyte image, before exposure to the sperm cell. Changes in imaging patterns were correlated with different maturation stages in the oocyte. Although the total protein content and mitochondrial DNA copy number were not associated with meiosis resumption, the optical density of the cytoplasm showed a positive correlation with those features. Using a single-cell sequencing approach, oocyte maturation was shown to be the key modulator of transcriptomic fingerprint, describing variations in sibling human oocytes based on transcript variability. Interestingly, mature oocytes classified with the i-CARE ranking tool showed differential expression of PLCXD2, MT-ND1, PACS1, DOT1L and MIK67; suggestive that oocytes with lower competence may have a compromised cell cycle either by non-reparable DNA damage or insufficient ooplasmic maturation, consistent with the pathways described in human and mouse models
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The efficiency of modulation contrast microscopy image analysis as a predictive tool for human oocyte quality |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10185179 |
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