Crosstalk between neuroendocrinology and follicular dynamism: the mare experimental model for reproductive “aging” in women

Abstract

The study of reproductive physiology in relation to advancing age is of great interest and involves many species, evaluating the mare as a potential model to study follicular and oocyte maturation in the woman. As in women, the mare has a comparable timing with the events associated with follicular and oocyte maturation, having a long follicular phase, a large follicle size, and the timing between human chorionic gonadotrophin (hCG) o equine chorionic gonadotrophin (eCG) administration and ovulation nearly superimposable. Follicular dynamism is characterised by three functional moments whose endocrine mechanisms dictate their physiological sequence of events: Recruitment, selection and dominance. Aging had caused profound functional alterations at the ovarian level, counaltered luteal phase, LH and progesterone, reduced follicular phase, compensated by increased FSH and E₂, increased cycle duration and inter-ovulatory intervals, intermittent ovulations, and increased pool of growing primordial follicles, resulting in accelerated depletion of ovarian reserve.

This significant sequence of functional and neuroendocrine effects are the expression of impending reproductive senescence or menopause, respectively, in the mare and the woman in whom the reproductive life turns out to be twice as long as the mare. Aging thus represents a dissociation between oocyte maturation and ovulation, causes a decline in the quality of oocytes.

Older mares had lower androgen pattern than younger, showing that age induces reduction in androgens' synthesis in physiologically cyclic Spanish Purebred mares. In humans’ experimental animals’ and mares’over 16 years, components of the somatotropic axis, such as growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations, decrease with advancing age. Advanced age leads to a predominance of sympathetic nervous activity and lower serotonergic and dopaminergic activity in non-pregnant mares. The pivotal interaction between serotonin (5-HT) and calcium shift in aging pregnant and cyclic mares was recorded, with lower 5-HT, total calcium and ionized calcium in the oldest mares. Aging appears to reduce the secretory tone of 5-HT, with a concurrent large shift in calcium metabolism in pregnant mares. In woman and in animal models, as the mare, estrogens are involved in iron (Fe) homeostasis, supporting the hypothesis of the existence of an “estrogen-iron axis”, with advancing aging. The correlation between thyroid hormones (TH) and ovarian pool was recorded. Ovulation representing a controlled inflammatory process is also mediated by the intervention of glucorticoids, especially cortisol. The ovary is the target tissue for glucocorticoids in many species, including women and mares, but it does not synthesize cortisol de novo.The use of in vivo rather than in vitro models, with a positive impact on unique human, animal and environmental health, is a desirable application for future research in this field.