Acute UV effect on epidermal transcriptome profiling in male and female Wild Type (SKH-1/SV129/BL6/J) mice and deficient for PPARbeta (SKH-1/SV129/BL6/J PPARD-/-) littermates.

UV irradiation is the most mutagenic and carcinogenic factor identified in non-melanoma skin cancers. Indeed, UV exposure can induce DNA damage in skin cells. However, cells are able to remove these lesions through DNA Damage Response mechanisms, thus avoiding mutagenic DNA lesions. In parallel to this DNA repair pathway induction, cell cycle arrest is induced to allow time to repair or to undergo apoptosis, in this case the UV-induced damage is irreversible. UV exposure has also a mitogenic action by stimulating cell survival and proliferation leading to epidermal hyperplasia. All these intrinsic cellular events induced in response to UV exposure have not been characterized in a sex-dependant context. To explore the key early stages before cancer initiation we performed a single UV exposure experiment. In response to this single UV dose, less severe epidermal atypia was observed in males compared to females.Epidermal transcriptomic data of UV-exposed male and female wild type (SKH-1/SV129/BL6/J)show that in average 12% of genes dysregulated in response to UV are sex-specific. The expression of some transcription factors involved in cell proliferation control are down regulated only in female wild type mice, in response to UV compared to wild type males. Notably, we observed a UV-sex-specific signature in male and female PPARb deficient mice (SKH-1/SV129/BL6/J PPARD KO)suggesting that this nuclear receptor could be involved in the sex-specific response to acute UV exposure. These transcriptomic data obtained in the epidermis from two sexes will help to understand why females are better protected than males from the risk of developing cSCC.