Researchers at The Institute reveal how a lipid signaling pathway regulates sperm function, paving the way for innovative diagnostics
SOURCE: The Research Institute of the McGill University Health Centre (The Institute)
February 5, 2025
Infertility affects millions worldwide, yet 34% of men with infertility receive no clear explanation for their condition. A new study by researchers at The Institute sheds light on a crucial piece of the puzzle: the molecular mechanisms underpinning the sperm’s ability to fertilize an egg.
Led by Cristian O’Flaherty, DVM, PhD, Senior Scientist in the Child Health and Human Development program (CHHD) at The Institute, the study explores sperm capacitation—the process by which sperm become capable of fertilization. Published in Human Reproduction, the research identifies a key role for sphingosine-1-phosphate (S1P), a lipid molecule, in regulating this process.
The researchers discovered that S1P stimulates the production of nitric oxide (NO), a signaling molecule essential for sperm function. “Until now, we didn’t know how NO production was regulated in sperm,” explains Steven Serafini, a PhD candidate in Dr. O’Flaherty’s lab and co-author of the study. “We found that S1P activates the PI3K/AKT pathway, which in turn triggers nitric oxide synthase, the enzyme responsible for NO production.”
These findings have important implications for understanding male infertility. During ejaculation, sperm are exposed to sphingolipids in seminal plasma. Disruptions in this process—such as those caused by obesity, which alters lipid levels in the blood—may impair sperm capacitation and contribute to infertility.
“Abnormal lipid content could be one of the hidden causes of male infertility,” says Dr. O’Flaherty. “Since obesity is linked to higher fat levels in the blood and reproductive organs, it may negatively impact sperm function in ways we are only beginning to understand.”
As obesity rates continue to rise, particularly among men of reproductive age, this research highlights the need to consider lipid metabolism in fertility assessments. By uncovering the molecular mechanisms linking lipid signaling to sperm function, this study paves the way for improved diagnostic tools that could analyze lipid profiles in infertile men.
“These findings bring us closer to identifying unknown causes of male infertility and developing better diagnostic strategies,” adds Dr. O’Flaherty. “We hope this research leads to modernized fertility assessments and new options for men facing unexplained reproductive challenges.”
About the study
Sphingolipids modulate redox signalling during human sperm capacitation. Serafini S., O’Flaherty C. Hum Reprod 2024, in press. PMID: 39658334.