Ovary

Critical Role of Insulin-like Growth Factor System in Follicle Selection and Dominance in Mares

Abstract
The role of the insulin-like growth factor (IGF) system in the deviation in growth rates among follicles (follicle selection) was studied in mares, using an IGF binding protein (BP) to reduce the follicular-fluid concentrations of IGFs. The future dominant follicle (F1) was treated by intrafollicular injection at the expected beginning of deviation (F1 20 mm; Day 0). The experimental groups were control (no injection, n=8), vehicle (injection of vehicle; n=6), and BP (injection of 250 µg of recombinant human IGFBP-3; n=6). A sample of follicular fluid was taken from F1 on Day 1 in all groups. Compared to the control group, IGFBP-3 reduced (P < 0.05) the follicular-fluid concentration of free IGF-1 by 90%; lowered (P < 0.05) the concentrations of estradiol, activin-A, inhibin-A, and vascular endothelial growth factor; and increased (P < 0.05) the concentration of androstenedione. Diameter of F1 decreased and diameter of F2 increased after Day 0 in the BP group, compared to the control and vehicle groups. A greater (P < 0.05) increase in circulating concentrations of FSH between Days 0 and 1 occurred in the BP group than in the other groups and accounted for the increased growth of F2. Dominance and ovulation from F1 occurred from fewer (P < 0.03) mares in the BP group (1 of 6) than from the control and vehicle groups combined (11 of 14); the remaining mares in the BP group ovulated from F2. Results indicated that the IGF system has a critical intrafollicular role in the differential changes in concentrations of follicular-fluid factors between the future dominant and subordinate follicles, leading to the development of follicle dominance (selection) and ovulation in mares.

Key words: Ovary • Cytokines • Follicular development • Growth factors • Steroid hormones

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