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Title: Experimental and cytological studies of mammalian fertility and infertility with particular reference to the ageing ovary
Author: Gosden, R. G.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1988
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Reproduction and ageing are processes in which biological order and organization vary over time. Arguably, neither is a biological discipline in its own right but both involve many branches of science: from molecular aspects, through studies of the whole organism to an appreciation of the behaviour of communities. In both fields, therefore, an interdisciplinary attitude is advantageous and has influenced the course of my research programme. Investigations of the ageing reproductive system and the developmental biology of ovarian follicles have involved cytology and cytogenetics, endocrinology, experimental surgery and mathematical modelling. Maternal age is a major factor affecting the prospect and outcome of pregnancy in animals and man. Inbred mice have been used as subjects of most sudies for practical reasons and because they are good models for mammalian development and ageing. Pregnancy losses in mid-life are attributable to increased numbers of cytogenetically abnormal embryos and a decreased uterine capacity for maintaining conceptuses to full term. The cause(s) of aneuploidy in older mothers remains unknown although the integrity of the meiotic spindle is in question since it disintegrates during 'lq overripening of oocytes in the fallopian tube and is altered in preovulatory oocytes of older mothers. Experimental delay of ovulation does not affect the incidence of anomalies but unilateral ovariectomy causes the peak incidence of anomalies and subsequent sterility to occur prematurely, indicating tht biological and chronological age can be uncoupled. However, many normal conceptuses fail to thrive in older mothers. The uterus undergoes structural changes as a result of ageing and parity, but the functional significance of these, if any, is not known. The endocrinology of pregnancy requires further study for, while luteal function may be unimpaired, there is mounting evidence of age changes in tissue responsiveness and of detrimental effects of long-term exposure to cycles of ovarian hormone stimulation. Ovarian oocytes disappear continuously throughout life because of recruitment for growth and ovulation,and cell death. Whereas sterility in some rodents is due to inability to produce an ovulatory surge of gonadotrophic hormones, in others it is depletion of oocytes, as in humans, that is primary. The rate of ooctye depletion and the size of the initial store define the ultimate limit for fecundity. Exponential functions which define the rates of follicle attrition change according to age and physiological state. The number of follicles at puberty are related allometrically to body weight, and the early age of menopause in our species may have arisen adventitiously as longevity evolved beyond expectations based on body weight. New techniques have been employed to investigate the control of ovarian follicle recruitment, growth/death and morphogenesis of the antrum. Mathematical models indicate that the profile of follicle stages in mice of different ages and genotypes is mainly influenced by death ('lq atresia) rates which are the highest in small and large follicles. The granulosa epithelium, which originates from a small number of clones, controls the formation of the antrum. Antral fluid appears to consist of local metabolites and plasma constituents; its formation probably involves more than one mechanism. Organotypic cultures may provide the best prospect of furthering investigation of morphogenesis of the Graafian follicle and of the cellular basis of follicle dynamics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available