Temperature controls mechanism in sperm linked to male fertility

The mobility of sperm appears to be temperature-dependent due to the action of a single protein, according to research carried out in mice.

Researchers from Washington University School of Medicine, St Louis, Missouri used techniques originally developed to study brain cells to show that electrical discharges from a particular sperm protein, CatSper, increased when the temperature surrounding the cell surpassed 38 degrees Celsius. In parallel, sperm behaviour switched from a smooth swim-like motion used for navigation to hyperactive propellor movements needed for entry into the egg.

'That hyperactive state in sperm is key for successful fertilisation, and no one knew exactly how temperature triggers it,' said professor of cell biology and physiology Polina Lishko, corresponding author of the paper published in the journal Nature Communications.

Previous research suggested sperm mobility changes may be activated by environment pH or reproductive hormones like progesterone (see BioNews 1078, 1102 and 1121).

While the study was done in mice, the CatSper protein is common to all mammals, and previous research has linked mutations in the CatSper gene to human male infertility. The protein regulates calcium ion entry into sperm cells, thereby controlling the sperm tail motion.

Because most mammals – including humans – create and store sperm in testes around two to four degrees lower than the body temperature, the researchers hypothesised that reaching the warmer internal female reproductive tract might activate CatSper.

Professor Lishko suggested the findings may offer new approaches to male contraception and infertility treatments, with previous attempts to target the protein proving unsuccessful: 'Instead of creating inhibitors, it might be possible to activate CatSper with temperature, thus prematurely switching on this channel to drain the sperm of energy, so that by the time the sperm cell is ready to do its job and enter the egg cell, it is powerless.'

The study also revealed that the pH of the testes and an additional ejaculate molecule, spermine, both appear to shield CatSper from warmer temperatures to prevent sperm activating before reaching the egg.

The authors drew on evolutionary observations that species without the CatSper proteins, such as birds, have internal testes where temperature-activation is redundant. They also highlighted that men with varicocele – an overgrowth of blood vessels leading to increased testicular temperature – show impaired sperm motility which can lead to infertility. However, whether CatSper is the mechanism by which variocele affects fertility remains unknown.