Rattus norvegicus intrauterine microbiome (16S)

The possible association of changes in intrauterine microbiota with intrauterine adhesions (IUA) has not been studied. In this research, rat models were 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 Mycoplasma pulmonis was markedly abundant in IUA samples. Metabolic analysis suggested that most of the IUA-enriched 58 metabolites and all the IUA-diminished metabolites were associated with M. pulmonis abundance. Moreover, rat IUA metabolic profiles shared much similarity to human IUA. Transcriptomics analysis of the IUA endometrial tissue revealed high level of DNA sequence for the gene Tenascin-N which codes for a protein associated with the extracellular matrix of wounds, while transcription levels of key genes involved in the production of Leydig cells and trophectoderm cells, and in immortalization of activated T cells and monocytes were low. Treatment for IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN), respectively, did not reduce the incidence of IUA, though the transcriptional level of IL-6 was dramatically down-regulated (96%-86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse and B cell receptor signaling pathway was highly up-regulated, and the proportions of Ulvibacter in the E2 group and Staphylococcus in the OTC group were significantly increased. Our findings identify an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA.