Fig. 7: Estrogen-induced cervical/vaginal carcinogenesis in transgenic mice expressing HPV16 induces an imbalance in the vaginal microflora. | Nature Communications

Fig. 7: Estrogen-induced cervical/vaginal carcinogenesis in transgenic mice expressing HPV16 induces an imbalance in the vaginal microflora.

From: HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources

Fig. 7: Estrogen-induced cervical/vaginal carcinogenesis in transgenic mice expressing HPV16 induces an imbalance in the vaginal microflora.The alternative text for this image may have been generated using AI.

a Schematic representation of the mouse reproductive tract. The morphology of the squamous epithelium lining the cervix/vagina and vulva in K14-HPV16 and control (FVB/n) mice is shown. Both the increased percentage of proliferative (Ki-67-positive) cells and the thickening of the epithelium in case of HPV16 oncogene expression should be noticed. b mRNA level of SLPI, S100A7, mouse orthologs of HβD1-3 (mβD1, mβD4, mβD14) and HD-5/6 (mβD12, mβD15) was measured by RT-qPCR. Microdissected frozen squamous epithelia from FVB/n and K14-HPV16 mice were analyzed. Each experiment was normalized to the amount of both HPRT and GAPDH mRNAs from the same sample. Results represent the means ± SEM of ten independent experiments. c Bacterial intrinsic diversity (reciprocal Simpson biodiversity index) and richness (deduced from Chao1 index). The reported values (at the genus level) for each individual mouse in the four defined groups [FVB/n (week 0 versus week 12) and K14-HPV16 (week 0 versus week 12)] are shown (n = 12 per group). The means ± SD are represented. d Bacterial α-diversity, genus richness and evenness (Simpson index) for K14-HPV16 mice. Data were separated depending on 17β-estradiol treatment duration [week 0 (n = 12) versus week 12 (n = 12)] and preneoplastic lesion grade [hyperplasia/LSIL (n = 6) versus HSIL (n = 6)]. The means ± SD are represented. e β-diversity of the vaginal microbial profile in K14-HPV16 mice was visualized using a Bray-Curtis dissimilarity matrix-based non-parametric dimensional scaling (NMDS) model (three dimensions). f Stacked bar charts depicting the relative abundance of the twelve main bacterial orders detected in control (FVB/n) and K14-HPV16 mice by 16 S V5-V6 amplicon sequencing. Relative abundance of bacteria belonging to the order of Pasteurellales g and Lactobacillales h in K14-HPV16 mice depending on 17β-estradiol treatment duration [week 0 (n = 12) versus week 12 (n = 12)] and HPV-related lesion grade [hyperplasia/LSIL (n = 6) versus HSIL (n = 6)]. The means ± SEM are represented. The comparison of relative abundance of bacteria in paired (week 0 versus week 12) lavage samples is also shown. The scale bar represents 100 μm. P values were determined using two-sided unpaired t-tests b and non-parametric Kruskal-Wallis test corrected with a two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli c, d, g, h. ns: not significant (p > 0.1). Source data are provided as a Source Data file.

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