Male infertility: tales of progress and frustration

This article describes andrology research, inspired by Professor Michael Hull, to develop sperm function tests and to understand the basic causes of male infertility. No generally acceptable sperm function test has yet been devised. Computer-assisted semen analysis (CASA) proved of limited value in predicting the outcome of in vitro fertilization (IVF) although it was more useful in donor insemination. High intracellular Ca2+ activity, [Ca2+]i, is involved in decreasing motility in cryopreserved sperm. Capacitative calcium entry after depletion of intracellular stores may generate the sustained increase in [Ca2+]i that initiates the acrosome reaction. Our data support the presence of Ca2+ stores as thapsigargin increased [Ca2+]i in sperm in Ca2+ -free medium. Recent observations indicate that cAMP enhances capacitative calcium entry, acting upstream of emptying of the store. Excess reactive oxygen species (ROS) is an important cause of sperm pathology but at low concentrations ROS regulate capacitation. Our evidence shows that ROS are produced by leucocytes present in sperm suspensions. We have been unable to demonstrate that human sperm produce ROS. The relationship between ROS production and lipid peroxidation indicates that sperm from some men are resistant to lipid peroxidation, possibly because of better antioxidant defences. We conclude that the future of andrology lies in the identification of the basic causes of infertility and not in more detailed descriptions of the properties of semen.