A recent study by the Max Planck Institute for Multidisciplinary Sciences and the University of Bonn shows that pH plays a crucial role in sperm motility in sea urchins and salmon. A rise in pH activates the enzyme soluble adenylyl cyclase (sAC), which produces the messenger molecule cAMP and thereby regulates sperm movement. This mechanism may be widespread in many marine invertebrates and fish. The findings have now been published in the Journal Proceedings of the National Academy of Sciences.
To reach the egg after ejaculation, sperm rely on a complex array of molecular signals. A key player is the small intracellular messenger cAMP - without it, sperm remain literally stationary. cAMP makes the sperm tail beat rhythmically, similar to the kick of a swimmer, propelling the sperm forward. The tail also acts as a rudder to control direction. Sperm locate eggs via chemical signals, which they detect using special sensors called receptors on the tail. Without cAMP, sperm cannot move - a mechanism essential for fertility in humans and animals alike.
Universal Mechanism or Special Case?
In sperm, cAMP is produced by the enzyme sAC. In mammals, including humans, sAC is activated by high bicarbonate (HCO₃⁻) concentrations in semen and the oviduct. It was previously assumed that this mechanism is universal across the animal kingdom - from corals to humans. However, enzyme activation by bicarbonate may be specific to mammals, as researchers led by Benjamin Kaupp and Olivia Kendall discovered in studies on sea urchins and fish.
pH as a Regulator
Sea urchins are marine invertebrates living on the seafloor. They reproduce sexually by releasing sperm and eggs into the open water - a process called mass spawning.
“In sea urchin sperm, and generally in marine organisms with external fertilization like fish, bicarbonate-based AC regulation is unlikely because the concentration in seawater is up to ten times lower than in mammalian semen,” explains Kaupp, Emeritus Director at the Max Planck Institute for Multidisciplinary Sciences and Senior Professor at the LIMES Institute and the Excellence Cluster ImmunoSensation3 at the University of Bonn. “Our question was: if not bicarbonate, then what triggers sAC activation and the rise in cAMP?”
Kaupp and Kendall, in collaboration with researchers at the Center for Reproductive Medicine and Andrology, University of Münster, the Technical University of Berlin, and the MPI for Neurobiology of Behavior in Bonn, discovered that sAC in sea urchin sperm acts as a pH sensor: the enzyme is directly regulated by pH.
Higher pH Makes Sperm More Active
“Sperm are completely immobile in the testis. They only become motile after ejaculation. First, the pH rises, making the intracellular environment alkaline. This activates sAC, increasing cAMP levels. Chemical cues guiding sperm to the egg trigger a second pH rise, further sAC activation, and another cAMP increase,” reports Olivia Kendall, doctoral student at the University of Bonn and first author of the study now published in PNAS.
Two Key Roles for cAMP
The new results highlight the central role of cAMP in living organisms. Previous work by Kaupp’s group showed that in sea urchin sperm, cAMP activates pacemaker ion channels, which are widespread across the animal kingdom. In humans, these channels regulate rhythmic events such as the heartbeat. In sperm, the channels control rhythmic tail movements, allowing chemotaxis - the directed movement toward eggs.
“Summing up our current and previous findings, cAMP has two main functions: it initiates movement and serves as a key signaling molecule in chemotaxis,” explains Kaupp.
sAC as a pH Sensor in Fish
The pH-sensing role of sAC is not limited to sea urchins. Experiments in fish showed that higher pH also increases cAMP levels in salmon. Furthermore, the sAC from sea urchins and salmon lacks two amino acids found in the mammalian enzyme, which mediate the response to bicarbonate. These findings suggest that pH regulation is widespread among marine invertebrates and fish.
Why are there two fundamentally different regulatory mechanisms in nature? The key is environmental bicarbonate levels. “Regulation of sAC by either pH or bicarbonate represents an adaptation to environments with low or high bicarbonate concentrations,” says Kai Korsching, a former doctoral student in Kaupp’s team, now at the University of Münster.
Implications for Reproduction and Climate Change
The study’s findings are also relevant in the context of climate change. Because sAC in marine organisms is controlled by pH, ocean acidification could impair reproduction. “As lakes and oceans acidify due to rising atmospheric CO₂, the reproductive success of these species may be affected,” says Kendall.
Funding
The study involved the Max-Planck-Institute for Multidisciplinary Sciences, the University of Bonn, the Center for Reproductive Medicine and Andrology at the University of Münster, the Technical University of Berlin, and the MPI for Neurobiology of Behavior in Bonn.
Publication
O. Kendall, O.T. Hoang, J.L. Wort, H. Hamzeh, H.G. Körschen, R. Pascal, K. Korsching, M. Wu-Lu, W. Bönigk, C. Kambach, L. Alvarez, R. Seifert, T. Strünker, M.A. Mroginski & U.B. Kaupp, Soluble adenylyl cyclase in nonmammalian sperm is directly controlled by pH, not by HCO3− or Ca2+, Proc. Natl. Acad. Sci. U.S.A. 123 (5) e2505026123. DOI: https://doi.org/10.1073/pnas.2505026123
More information
Press release of the Max-Planck-Institute for Multidisciplinary Sciences: https://www.mpinat.mpg.de/5210907/pr_2602
Contact
Prof. Dr. U. Benjamin Kaupp
Head of the Emeritus Group “Biophysics of Cellular Signal Transduction”
Max-Planck-Institute for Multidisciplinary Sciences
Senior Professor, LIMES Institute, University of Bonn
Email: u.b.kaupp@caesar.de
Phone: +49 228 9656100
