For some amphibians, like salamanders and newts, losing a limb is not a big deal. But why mammals don’t share the ability to regrow limbs after amputations has been hard to explain.
One theory involves differences in environment. Because amphibians rely heavily on water in their early stages of development, biologists suggest that lower oxygen levels may play an important role in kick-starting limb regeneration.
To find out if that’s the case, researchers from the Swiss Federal Institute of Technology in Lausanne exposed tadpoles and embryonic mice to different levels of oxygen after limbs were amputated. While the mouse embryos didn’t fully develop new limbs from scratch, the study, published in Science, noted a significant difference: wounds closed faster, and cells entered the first stages of regeneration, even activating regeneration-related genes.
“We are very excited about our findings,” said study co-author Can Aztekin in a press release. “By directly comparing species that can and cannot regenerate, we bring a fresh perspective to a centuries-old question.
Early Stages After Losing a Limb Are Critical
The first step after a limb is lost, and when potential regrowth can begin, is wound healing. And this is where the first differences between amphibians and mammals appear. In salamanders and other limb regenerators, wounds seal quickly, and cells responsible for regeneration activate almost immediately. Not so in mammals, where wounds don’t close as rapidly, and scars often form instead of kickstarting the regeneration process, even though they technically have the genetic tools for it.
“For a long time, regeneration research focused on amphibians, while mammalian regeneration was rarely examined experimentally side by side in a comparable manner,” said Aztekin. “Although many studies showed that regenerative species such as amphibians and mammals share similar genes, suggesting that mammals may retain a latent regenerative capacity, it remained unclear whether mammalian tissues can indeed activate limb regenerative programs, and what prevents them from doing so.”
To trigger mammals’ potential regenerative capacity, the team wanted to understand the role oxygen plays in the process, as amphibians are significantly more exposed to low-oxygen environments than mammals during critical life stages. In their study, the researchers amputated developing limbs from tadpoles and mouse embryos and observed the amputated limbs under varying oxygen conditions.
Read more: Axolotls Can Regrow a Key Organ From Scratch, Allowing Immune Cells to Fight Infections
Low Oxygen Levels Favor Wound Healing
The researchers tracked wound closure and how cells behaved overall, especially changes in DNA activity. One important marker they monitored was the cellular oxygen sensor HIF1A, a protein that activates healing and regeneration under low-oxygen conditions.
The experiments proved particularly interesting. The team reported that lower oxygen levels induced faster wound healing in mouse cells and triggered genetic signs of early regenerative steps. Surprisingly, the tadpoles maintained their regenerative capacity across different oxygen levels, even at concentrations above normal air. A closer look at HIF1A showed it remained relatively active across a wide range of oxygen conditions, likely supported by the tadpoles’ distinct genetic makeup.
When extending their analysis to HIF1A behavior in axolotls and humans, the pattern held. It appears that mammals have a stronger response to oxygen levels, which leads to regenerative processes being turned off shortly after injury.
Better Wound Healing Under the Right Conditions
These findings support previous research on mammals’ capacity to regenerate body parts but, for the first time, draw a clear connection to a specific environmental factor: oxygen levels.
Understanding this could one day lead to better approaches to wound healing and potentially improve regenerative processes in humans. And while it’s unlikely that humans will regrow full limbs anytime soon, it’s worth noting that molecular processes once thought to be set in stone may be more flexible than expected — if the conditions are just right.
"Our results show that regenerative programs can be triggered in mammalian tissues and begin to outline a clear, testable path toward promoting limb regeneration in adult mammals,” said Aztekin.
This article is not offering medical advice and should be used for informational purposes only.
Read more: When It Comes to Healing Wounds, Yogurt Could Be a Game-Changer
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April 9, 2026 at 04:23PM