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Title: Studies on the acquisition, expression and disruption of mammalian sperm motility
Author: White, David Robert
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1987
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Mammalian spermatozoa attain the ability to initiate progressive motility during their passage through the epididymis. In many species the movement characteristics of these cells are further modified in the female tract to produce a state of "hyperactivation", which is believed to facilitate penetration of the oocyte vestments, particularly the zona pellucida. The exact biochemical mechanisms involved in the development and expression of motility, and the way in which these processes are modified by potential contraceptive agents, such as sulphasalazine, gossypol and propranolol, remain unknown. Since published evidence implicates important roles for prostaglandins and the intracellular messengers cyclic 3',5' adenosine monophosphate (cAMP), calcium and pH in this context, this study investigated the involvement and interplay of these factors in the aquisition and expression of sperm movement. In contradiction to previously published data in other species, cAMP levels were found to be higher in immotile caput epididymal spermatozoa, than in caudal epididymal spermatozoa, both in undiluted form and upon release into appropriate media. Both cell types expressed a rapid calcium dependant, calmodulin-independent increase in cAMP content upon dilution to a concentration of 20 million spermatozoa/ml. This initial rise was abolished by dilution to one million/ml. Further investigations revealed that the rapid elevation of cAMP levels at the higher cell concentration was due to a factor present in epididymal plasma which may be a phosphodiesterase inhibitor. A more gradual increase in cAMP levels does occur in capacitating caudal spermatozoa incubated at this lower density, whilst caput levels remain low. This elevation precedes the appearance of hyperactivation, which, in turn, precedes the induction of the acrosome reactiion. Both hyperactivation and the rise in cAMP levels are abolished by incubation in medium with no added calcium (NAC). Neither phenomenon restored by the addition of the phosphodiesterase inhibitor isobutyl methyl xanthine (IBMX), although similar treatment of caudal spermatozoa in medium MT-1 (containing 1.7mM calcium) increased cAMP levels, stimulated percentage motility and advanced the appearance of hyperactivation. Addition of a membrane permeant analogue of cAMP to caudal spermatozoa in NAC also failed to evoke hyperactivation, whereas it mimicked the action of IBMX on caudal spermatozoa in MT-1. cked the action of IBMX on caudal spermatozoa in MT-1 Incubation of caudal spermatozoa in MT-1 with the calmodulin antagonist calmidazolium slightly reduced cAMP levels and totally abolished coordinated sperm movement. Addition of IBMX in the presence of calmidazolium increased cAMP content to levels higher than those expressed in MT-1 alone, but did not restore coordinated motility. To determine why caput spermatozoa failed to show an elevation of cAMP levels during prolonged incubation, as well as the mechanisms responsible for this increase in capacitating caudal spermatozoa, intracellular calcium concentration and pH were determined for both cell types. No overt difference in calcium content or internal pH exists between caput and caudal spermatozoa, with both cell types exhibiting a rise in calcium levels and a fall in pH over a time course of five hours. However, calcium levels declined significantly in caudal spermatozoa at the time when maximal levels of hyperactivation are being expressed. In addition to these fundamental studies, suggesting a role for cAMP in the expression of hyperactivation, the data published in this thesis also shed light on the mechanisms by which the contraceptive agents sulphasalazine, gossypol and propranolol influence sperm motility.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Sperm motility study