Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment

Abstract

Intrauterine adhesions (IUAs) have caused serious harm to women’s reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsis pulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M. pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96–86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins.

Human umbilical cord-derived mesenchymal stem cells and auto-crosslinked hyaluronic acid gel complex for treatment of intrauterine adhesion

“…ER binds with estrogen, triggering transcriptional activation and boosting cellular DNA and protein synthesis. Additionally, it increases the proliferation of endometrial epithelial cells, demonstrating the multifaceted role of these factors in IUA prevention [ 32 ].…”

The impact of oxygen content on Staphylococcus epidermidis pathogenesis in ocular infection based on clinical characteristics, transcriptome and metabolome analysis

“…Wald test was used to identify genes that were differentially expressed between two S. epidermidis groups. Differentially expressed genes (DEGs) were identified based on adjusted p value < 0.05 and |log2 FoldChange| > 1 as selection criteria as described in a previous study ( Wen et al, 2022 ). The cluster Profiler (version 4.2.2) package (Bioconductor, United States) was used to evaluate enrichment of the GO and KEGG in the sets of upregulated and downregulated genes separately ( Wu et al, 2021 ).…”

Arthrocolins Synergizing with Fluconazole Inhibit Fluconazole-Resistant Candida albicans by Increasing Riboflavin Metabolism and Causing Mitochondrial Dysfunction and Autophagy

“…Wald test was used to identify genes that are differentially expressed between every two sample groups. Differentially expressed genes (DEGs) were identified based on adjusted P value (BH) of <0.05 and |log2FoldChange (FC)| of >0 as selection criteria as described in a previous study ( 50 ). The clusterProfiler (version 4.2.2) package was used to evaluate enrichment of the GO and KEGG categories in the sets of upregulated and downregulated genes separately ( 51 ).…”