Sex hormones influence not only the reproductive system but also the skin’s ability to recover from injury. Biologists have found that in female mice, skin cells divide and mature in a more coordinated fashion, which helps explain why wounds heal faster in females than in males.
Human skin is constantly renewing itself. Its outer layer, the epidermis, sheds old cells and replaces them with new ones, thereby maintaining the body’s protective barrier. However, scientists have long debated whether the cells responsible for this renewal process are functionally equivalent.
According to one model, the dividing cells in the lower layer of the epidermis are roughly equivalent; some continue to multiply, while others mature and migrate toward the surface. In 2007, research on mice confirmed that the distribution of cell lineage sizes supports this hypothesis.
An alternative model proposes a hierarchy, in which stem cells maintain their own population while producing intermediate progeny capable of only a limited number of divisions. In 2012, researchers demonstrated that it is, in fact, stem cells that drive the long-term regeneration of the epidermis following an injury.
Understanding tissue repair depends on knowing which cells persist over the long term and which ones quickly exhaust their proliferative potential. In a new study, the authors employed a heritable fluorescent marker and repeated microscopic imaging to track the fate of individual cells and their descendants over nearly five months, directly within the skin of living mice. The findings were published in the journal Nature.
The developmental pathway toward a mature cell in the protective layer includes an intermediate stage, during which a cell begins to alter its genetic program while still retaining the capacity to divide. The study revealed that the behavior of these cell lineages depends on the sex of the animal. In females, daughter cells tended to act in a more coordinated fashion. Two cells originating from the same parent cell were likely to divide, mature, and exit the lower layer of the epidermis at roughly the same time; in males, this synchrony was less pronounced.
Having discovered this, the researchers investigated the role of hormones. They examined males after the removal of the testes—the primary source of testosterone—and observed a shift in cellular behavior toward the pattern characteristic of females. Administering an active testosterone derivative restored the male-typical pattern, demonstrating that these differences are driven by hormonal influence.
In females, the removal of the ovaries reduced stem cell proliferation and nearly eliminated signs of coordinated behavior among daughter cells. Administering estradiol restored cell proliferation; consequently, the researchers linked the action of estrogens to the maintenance of cell division, while associating male sex hormones with cell maturation and the exit of cells from the lower epidermal layer.
This was further confirmed by an experiment on regenerative capacity. In females, wounds closed more rapidly, particularly during the initial days of observation. This process was accompanied by an earlier activation of cells and a higher degree of coordination in their behavior; however, as healing progressed, the advantage observed in females diminished.
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