The Bovine Model: Physiological Significance of the High Variation in Antral Follicle Count (AFC) during Ovarian Follicular Waves in Young Adults Cumulative age associated with menopause (1), onset of irregular menstrual cycles (2), end of fertility (3), and beginning of subfertility (4). te Velde et al., 1998. Mol Cell Endo. 145:67-73. * * * * * * * * * * * * Ovarian Reserve FSH & LH Ovarian Reserve FSH & LH Healthy Degenerated Primordial 1000 X Transitory 1000 X Primary 1000 X Secondary 400 X Antral 400 X *** Variation in Number of Morphologically Healthy Oocytes/Follicles in Calves and Heifers: – 10,000 to 350,000 – 1,920 to 51,520 Does high variation in ovarian reserve impact fertility? Can new methods to predict, monitor and improve fertility be developed? Mechanisms? Therapies? Low Day 4 LH (ng/ml) 0.40 High 0.33 0.33 0.26 0.26 0.19 0.19 0.12 0.12 0.05 0.05 0 2:00 4:00 6:00 8:00 10:0012:00 Day 11 0.40 0 2:00 4:00 6:00 8:00 10:0012:00 Time P < 0.03, n = 11 animals Bovine model: Physiologically significant linkage exists, independent of aging, between the inherently high variation in AFC during follicular waves with size of gonads, ovarian reserve, gonadotropin secretion and action, ovarian function, oocyte quality and uterine function, which may in turn impact fertility and reproductive longevity. Variation in Number of Morphologically Healthy Oocytes/Follicles in Calves and Heifers: – 10,000 to 350,000 – 1,920 to 51,520 Weight in pregnant heifers carrying a single female fetus Weight (kg) 650 600 550 500 Control (n=13) 450 Restricted (n=10) 400 -20 30 80 130 180 Day of pregnancy 230 280 At birth Body Weight (kg) • Not different at birth: gestation length, placenta weight, number of cotyledons, any measure of calf size, or birth weight (C 40 ± 1 kg vs R 39 ± 2 kg) 280 230 180 130 80 30 Control (n 13) 0 4 8 12 16 20 24 Age (weeks) 28 32 36 40 Mean number of follicles ≥3 mm at 7, 18 and 35 wks of age Mean Fol. No. ■ Restricted 30 25 20 15 10 ■ Control * * * 7 18 35 Age (weeks) t al Systolic (mm Hg) Blood pressure 160 Control Restricted 150 140 130 120 110 Diastolic (mm Hg) 100 puberty 80 70 60 50 40 15 20 25 30 35 40 45 50 55 Age (weeks) 60 65 70 75 80 85 Mossa et al Conclusions Bovine major is novel biomedical model(ovarian to elucidate Identified source of variation reserve) Phenotyping cattle based on AFC/AMH may be useful to causes and mechanisms whereby the high that is associated with marked alterations in ovarian improve experimental design,insuperovulation, and variation in ovarian reserve single-ovulating differentiation, function and responsiveness to perhaps (?) and function, health (?)fertility in cattle. species mayfertility altergonadotropins. ovarian and health of individuals. “Not everything that counts can be counted, and not everything that can be counted counts” Sign hanging in Einstein’s office at Princeton
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