ANIMAL MODELS FOR THE STUDY OF HUMAN OVARIAN FUNCTION

Abstract

The study of ovarian function has been of great interest to scientists and clinicians in the human and veterinary health fields for more than 20 centuries. Initial studies of the ovaries were based on anatomical descriptions post-mortem, followed by histological and endocrinological approaches. The introduction of high-resolution ultrasonography provided a long-awaited tool to image the reproductive tissues in situ in both animals and humans. Critical studies of the characteristics and control of ovarian follicular and luteal dynamics in non-human primates, rodents, and domestic farm animals have involved frequent (i.e. daily or multiple times a day) blood sampling and ultrasonography. Studies of this nature in women are difficult, and often unethical to conduct. Differences in antral folliculogenesis between humans and animals appear to be more in detail rather than in essence, and may reflect differences in intrinsic physiology or merely differences in our ability to detect changes in a given species. In women, the presence of endometrial shedding and symmetric luteal and follicular phases are different from that observed during the estrous cycles of domestic farm animals but despite these differences, general similarities in antral follicular dynamics exist. A continuous pattern of antral follicle development was originally proposed in domestic livestock species; however, the use of frequent serial ultrasonography and simultaneous endocrine profiling in these animal species has resulted in a broad understanding of follicular wave dynamics. Follicular waves have now been described in every species in which this approach has been used, including humans. The relatively large diameters of antral follicles in cows and mares, compared to monkeys, sheep, and rodents provide greater feasibility for characterizing antral follicular dynamics ultrasonographically. Profound similarities in the dynamics of follicle development exist between the menstrual cycle in humans and the estrous cycle in cattle and horses. Despite a proportionately longer luteal phase in cows and mares, the growing phase of the dominant ovulatory follicle (defined as the time period from wave emergence to ovulation) is comparable in the human, cow, and mare. Thus, at present, cows and mares may be the most appropriate models for the study of antral follicular dynamics in women. While the use of animal models has increased our understanding of ovarian function and provides the hypothetical basis for studies in women, differences in vocabulary, culture, and research methodologies between scientists in predominantly human versus animal settings has hampered knowledge translation. These differences represent a systemic impediment to a broad understanding of ovarian function and limits progress and innovation in the development of safer and more efficacious treatments for infertility and contraception.