Lauren Fuge
A study in mice has found that warm temperatures in the reproductive tract trigger a “switch” that sends sperm into a hyperactive mode. This changes their motions from the smooth swimming necessary for navigation to the thrashing, twisting motions necessary to make it through the tough outer layer of the egg.
“That hyperactive state in sperm is key for successful fertilization, and no one knew exactly how temperature triggers it,” says Polina Lishko, a professor at Washington University School of Medicine in St. Louis, US. “Our work has identified a temperature-controlled switch in sperm that triggers these increased movements precisely when they are needed during fertilization.”
According to Lishko and colleagues, the discovery of this switch may lead to new approaches for male contraceptives, as well as treatments for male infertility.
Picky sperm
In mammals, including humans, sperm are heat-sensitive and tend to thrive when the ambient temperature is a few degrees below body temperature. Mammals have therefore evolved to keep male reproductive organs cooler than the normal core body temperature – at or below 34°C.
Some mammals with internal testes have developed ways to cool their sperm in ingenious ways. Dolphins, for example, pass blood through their dorsal fin to cool it before it heads to their testes. Elephants cool testes-bound blood in a similar way by passing it through their ears.
Humans keep their sperm cool by creating and storing it in external testicles. Previous research has shown that temperatures above 36°C are detrimental to fertility.
But here’s the puzzle: while sperm love to be cool, the female reproductive tract is a few degrees warmer than body temperature. Researchers have long wondered about how sperm are able to fertilise eggs in such uncomfortably toasty conditions, without any apparent adverse effect.
The new findings, published in Nature Communications, help solve this puzzle.
Opening the gate
The research focused on a protein called CatSper, which is embedded in the surface of sperm in all mammals.
It helps form a channel (or pore) that controls the movement of charged calcium atoms through the cell membrane, which drives the ‘hyperactivation’ of the sperm. This is characterised by vigorous movements in the sperm’s tail, needed to propel the sperm through the membrane of the egg during fertilisation.
This channel is critical for male fertility. Researchers have found that humans and rodents who lack CatSper are sterile.
Previous research had suggested that CatSper is activated by a combination of factors, including pH levels and progesterone (a reproductive hormone) in the female reproductive tract.
But Lishko and colleagues suspected there was also another controlling factor, and temperature was a likely culprit.
So they turned to lab mice to find out. Using micron-scale tools – first developed to study brain cells – they recorded what was happening in the mice’s reproductive systems.
Specifically, they watched the patterns of electric charges in individual sperm cells – patterns distinctive to when CatSper activates. There were clear spikes when the surrounding cell became hotter than 38°C.
The results indicate that CatSper is activated by temperature. Specifically, it triggers the hyperactive state of sperm when the ambient temperature matches that of the warm female reproductive tract.
“These results suggest that testicular externalization may have evolved, in part, to prevent premature CatSper activation and ensure male fertility,” the authors write in their paper.
Understanding the role of temperature in fertility may provide a more specific target for new male contraceptives.
Current attempts to develop contraceptives focus on deactivating the Casper channel are not yet effective, but Lishko says this discovery could provide new insights.
“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,” she says.