Publicação
Importance of microtubule cytoskeleton structure in oocyte competence
| Resumo: | Aneuploidy, the leading cause of infertility and failure In IVF treatment in women, results from errors during oocyte maturation, particularly aberrant meiosis. Crucial In this process is the meiotic spindle, a structure composed of microtubules and microtubule-associated pro- teins (MAPs) that together with the microtubule organizing center (MTOC), nucleate, stabilize, and ensure accurate microtubule spindle conformation during Metaphase I and Metaphase II. Unlike somatic and male germ cells, human oocytes eliminate the major microtubule organiz- ing center, the centrosome, during early oogenesis and assemble their spindle through unique mechanisms that are still poorly understood. Given the non-conserved nature of spindle as- sembly in female germ cells and the reliance on a recently identified huoMTOC for spindle stabilization in humans, exploring key microtubule proteins Involved In this process is essential. This study aims to characterize microtubule-associated proteins and actin-microtubule cross- linking proteins critical to spindle assembly in human oocytes, focusing on their localization at different stages of maturation: germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). Proteins that showed any specific enrichment at the MT spindle or cortex in oocytes were clas- sified as candidates. Given the scarcity of human oocytes, we used Drosophila oocytes as a model system for functional studies, employing RNA interference (RNAi) to deplete those promising candidate proteins involved in spindle assembly. Our approach provides insights into conserved spindle assembly mechanisms and identifies novel proteins with potential roles in regulating cytoskeletal dynamics during meiosis. Understanding these processes could ad- vance therapeutic strategies to reduce aneuploidy and improve fertility outcomes. |
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| Autores principais: | Grosu, Eugenia |
| Assunto: | Aneuploidy Actin MTOC Spindle |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Aneuploidy, the leading cause of infertility and failure In IVF treatment in women, results from errors during oocyte maturation, particularly aberrant meiosis. Crucial In this process is the meiotic spindle, a structure composed of microtubules and microtubule-associated pro- teins (MAPs) that together with the microtubule organizing center (MTOC), nucleate, stabilize, and ensure accurate microtubule spindle conformation during Metaphase I and Metaphase II. Unlike somatic and male germ cells, human oocytes eliminate the major microtubule organiz- ing center, the centrosome, during early oogenesis and assemble their spindle through unique mechanisms that are still poorly understood. Given the non-conserved nature of spindle as- sembly in female germ cells and the reliance on a recently identified huoMTOC for spindle stabilization in humans, exploring key microtubule proteins Involved In this process is essential. This study aims to characterize microtubule-associated proteins and actin-microtubule cross- linking proteins critical to spindle assembly in human oocytes, focusing on their localization at different stages of maturation: germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). Proteins that showed any specific enrichment at the MT spindle or cortex in oocytes were clas- sified as candidates. Given the scarcity of human oocytes, we used Drosophila oocytes as a model system for functional studies, employing RNA interference (RNAi) to deplete those promising candidate proteins involved in spindle assembly. Our approach provides insights into conserved spindle assembly mechanisms and identifies novel proteins with potential roles in regulating cytoskeletal dynamics during meiosis. Understanding these processes could ad- vance therapeutic strategies to reduce aneuploidy and improve fertility outcomes. |
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