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

Division of Agricultural and Environmental Sciences⁴ Division of Animal Physiology,⁵ School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, United Kingdom

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.

¹ B.N. was funded, in part, by the BBSRC (U.K.), and A.A.F.-N. was supported by Defra (U.K.).

² Correspondence: R. Webb, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, U.K. FAX: 00 44 115 951 6060; bob.webb{at}nottingham.ac.uk

³ Current address: Division of Infection, Inflammation and Repair, Mailpoint 810, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K

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