Fig. 8: Atrophy-linked genes being switched off in the vagina are associated with vaginal atrophy.

A The distribution of expression levels in the vagina of the seven switch-like genes implicated in vaginal atrophy. log(TPM + 1)_C represents values of log(TPM + 1) corrected for technical confounders. B Pairwise concordance rates (percentage of individuals in which the two genes are either both switched on or both switched off). C A schematic model for the etiology of vaginal atrophy. High levels of estrogen keep the driver genes switched on in basal and parabasal epithelium, impelling basal and parabasal cells to proliferate and mature, resulting in healthy vaginal mucosa. Conversely, low estrogen levels switch off the driver genes. The lack of basal and parabasal cell proliferation leads to a thin vaginal epithelium, resulting in vaginal atrophy. D Representative immunohistochemical staining of Arachidonate 12-Lipoxygenase (ALOX12) from healthy (\(n\) = 35) and atrophic (\(n\) = 28) vaginal tissues. Scale bars = 50 µm. We show healthy vaginal tissue from a woman with higher systemic estrogen levels and a thicker vaginal epithelial layer, along with atrophic vaginal tissue from a woman with low systemic estrogen levels and a thinner vaginal epithelial layer. There is no difference in ALOX12 expression in the basal or parabasal cells between healthy and atrophic epithelium groups, implicating it as a passenger gene. Images were taken with Axio Observer Z1 (Carl Zeiss AG) with a 20X objective. Panel C was designed entirely with BioRender. All panels were assembled as Fig. 8 in BioRender. Aqil, A. (2025) https://BioRender.com/l6mphqf.