Incipient ovarian failure associated with raised levels of follicle stimulating hormone and reduced levels of inhibin A in older sheep

In women there is a gradual rise in the basal level of follicle stimulating hormone (FSH) in the years prior to the menopause (pre-menopause) which is thought to be due to a relative lack of ovarian factors reflecting the number of antral follicles present in the ovaries. Experimental animal models for this phenomenon, particularly in mono-ovulatory species, have been lacking due to most animals' relatively short life span. We have available a group of experimental ewes in which the right ovary was removed and the left ovary was autotransplanted to the neck at least 10 years previously, which have been maintained in good health until an age of 12-13 years. Two experiments were conducted with these animals to determine the endocrine and follicular effects of age: a retrospective experiment in the same Finn-Merino ewes (n = 5) when the animals were 6-7 or 12-13 years of age; and a cohort experiment in old (12-13 years, n = 6) and young (2 years, n = 5) ewes of the same breed. In both retrospective and cohort experiments, the concentrations of FSH were significantly higher (P < 0.05) in older animals during the luteal phase when oestradiol secretion was low. This increase in FSH was associated with a decrease in the concentration of inhibin A (P < 0.05) in older animals in both the follicular and luteal stages of the cycle but the concentrations of oestradiol were similar between ages. Although there were significantly fewer antral follicles (P < 0.05) available for development in older ewes during the early luteal phase of the cycle, the ovulation rate was similar to that observed in younger animals (2.0 +/- 0 vs 2.0 +/- 4; p > 0.05) but the interval from luteal regression to the onset of the LH surge was longer (P < 0.05) in older animals. In conclusion, the endocrine changes associated with increasing reproductive age in sheep are therefore similar to those observed in women, suggesting that the sheep could be a useful animal model to study the effect of age on human fertility.