2004Biology of ReproductionRequires access

Relationship Between Low-Molecular-Weight Insulin-Like Growth Factor-Binding Proteins, Caspase-3 Activity, and Oocyte Quality1

Ben Nicholas, Ramiro Alberio, Ali A. Fouladi‐Nashta, R. Webb

Open publisher page 54 citations

Abstract

Bovine follicular atresia is associated with the apoptosis of granulosa cells and the subsequent loss of oocyte competence through the reduction of cellular contact (e.g., gap junctions). Several components of the insulin-like growth factor (IGF) system are thought to affect follicular atresia. Whereas the IGF-binding proteins (IGFBPs) are present in varying quantities throughout follicular development, IGFBP-5 appears to be present only during atresia, in parallel with its regulation in other tissue remodeling systems. However, to our knowledge, no connection has yet been made between atresia, low-molecular-weight IGFBP content, and oocyte quality in the bovine ovary. Caspases are actively involved in ovarian follicular atresia, and apoptosis in antral follicles is caspase-3-dependent. Hence, the aim of the present study was to investigate the use of these factors in the assessment of oocyte quality and developmental potential. Oocytes were aspirated, morphologically classified, and individually matured in vitro. The follicular fluid and granulosa cells of these follicles were analyzed for IGFBP profile and caspase-3 activity, respectively. A significant correlation was found between the presence of low-molecular-weight IGFBPs in bovine follicular fluid and caspase-3 activity of granulosa cells isolated from individual follicles. The highest percentage of development to the blastocyst stage was observed in oocytes from slightly atretic follicles. This group of oocytes contained an equal proportion of oocytes at grades 1-3. These data demonstrate that low-molecular-weight IGFBP profile is a more reliable method than the traditional morphological assessment of oocytes and can be used as an effective marker of developmentally competent oocytes. Importantly, these results have implications for the use of noninvasive follicular fluid markers in the selection of competent oocytes to improve outcomes of in vitro fertilization.

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Bovine follicular atresia is associated with the apoptosis of granulosa cells and the subsequent loss of oocyte competence through the reduction of cellular contact (e.g., gap junctions). Several components of the insulin-like growth factor (IGF) system are thought to affect follicular atresia. Whereas the IGF-binding proteins (IGFBPs) are present in varying quantities throughout follicular development, IGFBP-5 appears to be present only during atresia, in parallel with its regulation in other tissue remodeling systems. However, to our knowledge, no connection has yet been made between atresia, low-molecular-weight IGFBP content, and oocyte quality in the bovine ovary. Caspases are actively involved in ovarian follicular atresia, and apoptosis in antral follicles is caspase-3-dependent. Hence, the aim of the present study was to investigate the use of these factors in the assessment of oocyte quality and developmental potential. Oocytes were aspirated, morphologically classified, and individually matured in vitro. The follicular fluid and granulosa cells of these follicles were analyzed for IGFBP profile and caspase-3 activity, respectively. A significant correlation was found between the presence of low-molecular-weight IGFBPs in bovine follicular fluid and caspase-3 activity of granulosa cells isolated from individual follicles. The highest percentage of development to the blastocyst stage was observed in oocytes from slightly atretic follicles. This group of oocytes contained an equal proportion of oocytes at grades 1-3. These data demonstrate that low-molecular-weight IGFBP profile is a more reliable method than the traditional morphological assessment of oocytes and can be used as an effective marker of developmentally competent oocytes. Importantly, these results have implications for the use of noninvasive follicular fluid markers in the selection of competent oocytes to improve outcomes of in vitro fertilization.

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Available abstract

Bovine follicular atresia is associated with the apoptosis of granulosa cells and the subsequent loss of oocyte competence through the reduction of cellular contact (e.g., gap junctions). Several components of the insulin-like growth factor (IGF) system are thought to affect follicular atresia. Whereas the IGF-binding proteins (IGFBPs) are present in varying quantities throughout follicular development, IGFBP-5 appears to be present only during atresia, in parallel with its regulation in other tissue remodeling systems. However, to our knowledge, no connection has yet been made between atresia, low-molecular-weight IGFBP content, and oocyte quality in the bovine ovary. Caspases are actively involved in ovarian follicular atresia, and apoptosis in antral follicles is caspase-3-dependent. Hence, the aim of the present study was to investigate the use of these factors in the assessment of oocyte quality and developmental potential. Oocytes were aspirated, morphologically classified, and individually matured in vitro. The follicular fluid and granulosa cells of these follicles were analyzed for IGFBP profile and caspase-3 activity, respectively. A significant correlation was found between the presence of low-molecular-weight IGFBPs in bovine follicular fluid and caspase-3 activity of granulosa cells isolated from individual follicles. The highest percentage of development to the blastocyst stage was observed in oocytes from slightly atretic follicles. This group of oocytes contained an equal proportion of oocytes at grades 1-3. These data demonstrate that low-molecular-weight IGFBP profile is a more reliable method than the traditional morphological assessment of oocytes and can be used as an effective marker of developmentally competent oocytes. Importantly, these results have implications for the use of noninvasive follicular fluid markers in the selection of competent oocytes to improve outcomes of in vitro fertilization.

Key concepts: Follicular fluid, Oocyte, Follicular atresia, Biology, Follicular phase, Atresia, Endocrinology, Internal medicine

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