In mammals — ourselves included — sperm are unexpectedly selective regarding temperature, performing optimally in environments slightly cooler than average body warmth. Yet, considering the female reproductive tract’s higher temperature, how do these temperature-sensitive cells succeed in fertilizing an egg in such a warm setting?
Investigations from Washington University School of Medicine in St. Louis offer a solution: elevated temperatures — like those of the female reproductive tract — initiate a distinct signal that activates sperm, altering their behavior from smoother movements aimed at navigation to the vigorous and twisting motions required to penetrate the egg for fertilization. The identification of this signal presents a potential target for male contraceptives and interventions for male infertility.
Examining mice, the researchers revealed that a particular protein present in all mammals induces a hyperactive state in sperm when the surrounding temperature aligns with that of the female reproductive tract. These findings, shared in Nature Communications on April 17, also lend insight into the evolution of mammalian anatomy.
“This hyperactive state in sperm is crucial for successful fertilization, yet the precise mechanism by which temperature triggers it was unknown,” stated Polina Lishko, a BJC Investigator and professor of cell biology and physiology at WashU Medicine. “Our research has pinpointed a temperature-regulated switch within sperm that activates these enhanced movements exactly when they are necessary for fertilization.”
(Video courtesy of Polina Lishko)
WashU Medicine researchers have discovered a temperature-regulated switch in sperm cells that is essential for reproduction. In lower temperatures, mouse sperm move sluggishly (left). Conversely, at warmer temperatures typical of the female reproductive tract, sperm activity intensifies (right), enabling fertilization of the egg. The temperature sensitivity of this switch may explain why mammals evolved to maintain male reproductive organs at cooler temperatures than core body heat.
All mammals contain a specific protein on the surface of sperm known as CatSper. This protein regulates the influx of ions necessary to facilitate the hyperactive movements in the tail-like flagella that drive the sperm forward. Although the temperature activation of CatSper was previously unknown, it was thought to be triggered by a combination of pH levels in the female reproductive pathway and, in primates, by the hormone progesterone. However, this theory lacked robustness, Lishko commented, as most mammalian sperm do not react to progesterone, indicating an alternative factor must exist to activate the CatSper switch.
Temperature appeared to be a likely candidate. Evolution in mammals has ingeniously adapted ways to maintain male reproductive organs at or below 34 degrees Celsius (93.2 degrees Fahrenheit). For example, dolphins cool the blood directed to their internal testes by first routing it through their dorsal fin; elephants employ a similar cooling mechanism through their ears. The majority of other mammals, including humans, produce and store sperm in testicles situated outside of the body. Animals lacking these cooling adaptations, such as birds, do not possess CatSper proteins in their sperm.
Utilizing micron-sized tools and methodologies originally designed for studying brain cells, Lishko’s team tracked the unique electric charge patterns associated with CatSper activation in individual sperm cells, recording obvious spikes when the surrounding temperature exceeded 38 degrees Celsius (100.4 degrees Fahrenheit). Once CatSper was activated, the sperm’s motions shifted from gentle navigation to the vigorous activity required for egg penetration during fertilization.
Lishko emphasized that comprehending temperature’s influence on fertility may enhance male contraceptive methods and infertility treatments. Since CatSper is exclusive to sperm, targeting it would not interfere with other bodily functions. Efforts have been made to create contraceptives that deactivate this channel, yet Lishko noted that these attempts have largely been ineffective thus far. Insights from this research could lead to innovative strategies.
“Rather than developing inhibitors, it could be feasible to activate CatSper with temperature, prematurely turning on this channel to deplete the sperm of energy so that by the time the sperm is ready to fertilize, it is devoid of strength,” she elaborated.
Swain DK, Vergara C, Castro-Arnau J, Lishko PV. The essential calcium channel of sperm CatSper is temperature-gated. Nature Communications. April 17, 2025. DOI: 10.1038/s41467-025-58824-0
This study was funded by the BJC Investigator fund.
About Washington University School of Medicine
WashU Medicine stands as a premier institution in academic medicine, spanning biomedical research, patient care, and educational programs with a faculty of 2,900. Its research funding portfolio from the National Institutes of Health (NIH) ranks second among U.S. medical schools and has increased by 56% over the past seven years. Alongside institutional investments, WashU Medicine contributes over $1 billion annually to innovative research and training. Its faculty practice consistently ranks within the top five nationwide, employing more than 1,900 physician faculty across 130 locations, who also comprise the medical teams of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine boasts a rich history in MD/PhD training, dedicating $100 million recently to scholarships and program enhancements for its medical students, in addition to offering exceptional training in every medical subspecialty, as well as in physical therapy, occupational therapy, and audiology and communication sciences.
Initially published on the WashU Medicine website
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