Male and female mice renew their skin at different rates, governed by sex hormones
Male and female mice renew their skin at different rates, governed by sex hormones
Teams led by Cédric Blanpain (Université libre de Bruxelles) and Benjamin Simons (University of Cambridge) spent five months imaging the same labelled cells in the ear skin of living mice. Their Nature paper, published on 14 October 2026, reports that cells in the bottom layer of the epidermis divided more frequently in females than in males, mature cells took longer to leave this layer, and wounds on the back closed faster.
The epidermis continually renews itself: cells in its bottom layer divide, and their mature descendants move towards the surface and are shed. Studies have reached different conclusions about how many types of dividing cells this requires: a 2007 study involving Simons explained renewal with one type, while a 2012 paper by Blanpain and Simons identified two: stem cells and intermediate cells that have begun to mature but can still divide.
In the new study, the researchers activated a fluorescent label in a small number of cells in the bottom layer and imaged their clones, the descendants of each labelled cell, for 140 days: 1 171 clones across five females and five males. First author Dan Engelman said in a press release that the team had been looking for a cell hierarchy with stem cells at the top:
We were surprised to find substantial differences in how stem cells renew the skin in females and males.
The difference appeared in clone size: clones in females more often contained an even number of cells. This pattern can occur when sister cells, the two daughters of a single division, divide or leave the layer together, changing the clone size by two cells at a time. A model in which all dividing cells were equivalent could not reproduce the excess of even-sized clones. Data from both sexes fit a model in which sister cells act together and cells follow a sequence: a stem cell produces an intermediate cell, which undergoes a limited number of divisions before its descendants mature and leave the bottom layer.
According to this model, both daughter cells begin to mature after more than 95% of intermediate cell divisions in females, compared with 70% in males; a mature cell remains in the bottom layer for an average of 5,1 days in females and 3,0 days in males. Imaging every 12 hours confirmed that sister cells acted together in both sexes: a cell left the layer together with its sister in 45 of 46 cases in females and 42 of 50 cases in males.
The researchers tested the model's prediction that cells leave sooner in males by tracking labelled dividing cells: after 96 hours, one of the two daughter cells had left the bottom layer in 47% of pairs in males and 21% in females. Castration reduced this proportion in males to 14%; an implant containing the male sex hormone dihydrotestosterone raised it to 31%. A greater proportion of cells divide in females than in males (7,2% versus 5,6%), and estrogen sustains this rate: removing the ovaries reduced the proportion to 4,9%, and the excess of even-sized clones almost disappeared; estradiol, a form of estrogen, restored the proportion of dividing cells to 7,6%. In laboratory-grown human skin, dihydrotestosterone increased the proportion of labelled cells that moved into the upper layers within 72 hours to 37,2%, compared with 24,6%.
The researchers made a wound on each mouse's back: wounds closed faster in females, and on the second day the ring of dividing cells around the wound was wider, measuring 800 versus 590 μm in males. The authors attribute this to earlier activation and greater coordination of stem and intermediate cells in females: by the fourth day, clones in this ring were more often even-sized in females than in males.
Hormones had previously been linked to wound healing: in 1999, an estrogen patch accelerated wound healing in older women and men. That effect was attributed to inflammation; the new study shows in mice that hormones also affect epidermal stem cells.
Blanpain says the team will next compare the onset and progression of skin cancer in males and females.