Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment
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...
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MDPI AG
2022-07-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/7/784 |
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| author | Ya Wen Qunfu Wu Longlong Zhang Jiangbo He Yonghong Chen Xiaoyu Yang Keqin Zhang Xuemei Niu Shenghong Li |
| author_facet | Ya Wen Qunfu Wu Longlong Zhang Jiangbo He Yonghong Chen Xiaoyu Yang Keqin Zhang Xuemei Niu Shenghong Li |
| author_sort | Ya Wen |
| collection | DOAJ |
| description | 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 <i>Mycoplasm</i><i>opsis</i> specie in genital tract, murine lung pathogen <i>Mycoplasm</i><i>opsis</i><i>pulmonis</i> 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 <i>M.</i><i>pulmonis</i>, 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 <i>Tenascin-N</i>, 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 <i>Ulvibacter</i> or <i>Staphylococcus</i>. 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. |
| first_indexed | 2024-03-09T10:13:19Z |
| format | Article |
| id | doaj.art-51400b608a364d2498185e1991ccc137 |
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| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T10:13:19Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-51400b608a364d2498185e1991ccc1372023-12-01T22:32:48ZengMDPI AGPathogens2076-08172022-07-0111778410.3390/pathogens11070784Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine TreatmentYa Wen0Qunfu Wu1Longlong Zhang2Jiangbo He3Yonghong Chen4Xiaoyu Yang5Keqin Zhang6Xuemei Niu7Shenghong Li8State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaIntrauterine 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 <i>Mycoplasm</i><i>opsis</i> specie in genital tract, murine lung pathogen <i>Mycoplasm</i><i>opsis</i><i>pulmonis</i> 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 <i>M.</i><i>pulmonis</i>, 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 <i>Tenascin-N</i>, 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 <i>Ulvibacter</i> or <i>Staphylococcus</i>. 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.https://www.mdpi.com/2076-0817/11/7/784intrauterine adhesion (IUA)intrauterine microbiota<i>Mycoplasmopsis pulmonis</i> (<i>Mycoplasma pulmonis</i>)<i>Staphylococcus</i><i>Ulvibacter</i>tenascin |
| spellingShingle | Ya Wen Qunfu Wu Longlong Zhang Jiangbo He Yonghong Chen Xiaoyu Yang Keqin Zhang Xuemei Niu Shenghong Li Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment Pathogens intrauterine adhesion (IUA) intrauterine microbiota <i>Mycoplasmopsis pulmonis</i> (<i>Mycoplasma pulmonis</i>) <i>Staphylococcus</i> <i>Ulvibacter</i> tenascin |
| title | Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment |
| title_full | Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment |
| title_fullStr | Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment |
| title_full_unstemmed | Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment |
| title_short | Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment |
| title_sort | association of intrauterine microbes with endometrial factors in intrauterine adhesion formation and after medicine treatment |
| topic | intrauterine adhesion (IUA) intrauterine microbiota <i>Mycoplasmopsis pulmonis</i> (<i>Mycoplasma pulmonis</i>) <i>Staphylococcus</i> <i>Ulvibacter</i> tenascin |
| url | https://www.mdpi.com/2076-0817/11/7/784 |
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