Hyperactivated motility in human sperm

: regulation, function and significance in IVF

Abstract

Hyperactivation is a movement pattern elicited by sperm in the female reproductive tract. The transition to hyperactivated movement is characterised by an increase in amplitude and a decrease in symmetry of flagellar bending. The resulting forceful, unequal waveforms produce a swimming style that is erratic and often non-progressive. Linked temporally with the process of capacitation, hyperactivation is thought be a pre-requisite for fertilisation. Its putative roles are in navigation and movement through the oviduct, infiltration of the cumulus oophorus and penetration of the zona pellucida. The majority of evidence for the requirement for mammalian hyperactivation has emerged from studies in the mouse and the hamster, however a number of clinical studies in humans have also suggested that its expression is linked to male fertility both in vivo and in vitro. The expression of hyperactivation appears to be controlled both by Ca2+ entry through plasma membrane CatSper channels and by Ca2+ release from intracellular stores. Using CASA, the efficacy of pharmacological agents known to influence hyperactivation was assessed, and a robust hyperactivation assasy was developed. The assay was used both to explore the incidence of hyperactivation in fertile and infertile populations of men, and to attempt to define the prognostic potential of a pre-IVF hyperactivation screen. Whilst sperm from men undergoing ICSI treatment exhibited lower levels of hyperactivation than sperm from men in whom no semen abnormalities could be identified, there was no correlation between hyperactivation and fertilisation rate in conventional IVF. In the final set of experiments, an attempt to affirm the role of store-operated Ca2+ entry in hyperactivation was made, however drugs known to modulate this pathway did not influence any sperm motility parameters.

Date of Award	2011
Original language	English
Awarding Institution	University of Dundee
Supervisor	Christopher Barratt (Supervisor)