{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:09:50Z","timestamp":1790230190059,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01HD099091"],"award-info":[{"award-number":["R01HD099091"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The disturbed vaginal microbiome defined as bacterial vaginosis (BV) and the parasitic infection by Trichomonas vaginalis (TV), the most common non-viral sexually transmitted pathogen, have well-established adverse effects on reproductive outcomes and susceptibility to infection and cancer. Molecular mechanisms underlying these associations and the failure of antibiotic therapy to mitigate adverse consequences are not fully elucidated. In an in vitro human vaginal colonization model, we tested the hypothesis that responses to TV and\/or BV-bacteria will disrupt the micro(mi)RNA cargo of extracellular vesicles (EV) with the potential to modify pathways associated with reproductive function, cancer, and infection. miRNAs were quantified by HTG EdgeSeq. MiRNA differential expression (DE) was established in response to TV, the BV signature pathobiont Prevotella bivia and a homeostatic Lactobacillus crispatus with adjusted p &lt; 0.05 using R. Validated gene targets, pathways, protein-protein interaction networks, and hub genes were identified by miRWalk, STRING, Cytoscape, and CytoHubba. In contrast to L. crispatus, TV and the BV pathobiont dysregulated a massive number of EV-miRNAs, over 50% shared by both pathogens. Corresponding target pathways, protein interaction clusters and top hub genes were related to cancer, infectious disease, circadian rhythm, steroid hormone signaling, pregnancy, and reproductive tissue terms. These data support the emerging concept that bacteria and parasitic eukaryotes disturbing the human vaginal microbiome may impact reproductive health through EV-miRNA dysregulation.<\/jats:p>","DOI":"10.3390\/microorganisms11030551","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:59:16Z","timestamp":1677038356000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The microRNA Cargo of Human Vaginal Extracellular Vesicles Differentiates Parasitic and Pathobiont Infections from Colonization by Homeostatic Bacteria"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9293-9773","authenticated-orcid":false,"given":"Paula Fernandes Tavares","family":"Cezar-de-Mello","sequence":"first","affiliation":[{"name":"Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanthia","family":"Ryan","sequence":"additional","affiliation":[{"name":"Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-5735","authenticated-orcid":false,"given":"Raina N.","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","first-page":"e26310","article-title":"Coevolution of the Human Host and Gut Microbiome: Metagenomics of Microbiota","volume":"14","author":"Shahab","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s13668-022-00420-5","article-title":"Diet, Microbes, and Cancer Across the Tree of Life: A Systematic Review","volume":"11","author":"Kapsetaki","year":"2022","journal-title":"Curr. Nutr. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3233\/JAD-215224","article-title":"Relationship Between the Gut Microbiota and Alzheimer\u2019s Disease: A Systematic Review","volume":"87","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1007\/s00431-022-04383-1","article-title":"The hidden universe of human milk microbiome: Origin, composition, determinants, role, and future perspectives","volume":"181","author":"Consales","year":"2022","journal-title":"Eur. J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41467-017-00901-0","article-title":"The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases","volume":"8","author":"Chen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1128\/CMR.00075-15","article-title":"The Human Microbiome during Bacterial Vaginosis","volume":"29","author":"Onderdonk","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nature06244","article-title":"The Human Microbiome Project","volume":"449","author":"Turnbaugh","year":"2007","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"790627","DOI":"10.3389\/fcimb.2021.790627","article-title":"The Microbiome as a Key Regulator of Female Genital Tract Barrier Function","volume":"11","author":"Plesniarski","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/1471-0528.14390","article-title":"Why do lactobacilli dominate the human vaginal microbiota?","volume":"124","author":"Witkin","year":"2017","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/JCM.00851-09","article-title":"Quantitative PCR Assessments of Bacterial Species in Women with and without Bacterial Vaginosis","volume":"48","author":"Lillis","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","first-page":"79","article-title":"Nugent score related to vaginal culture in pregnant women","volume":"98","author":"Delaney","year":"2001","journal-title":"Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.immuni.2015.04.019","article-title":"Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract","volume":"42","author":"Anahtar","year":"2015","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajog.2018.12.011","article-title":"Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: Systematic review and meta-analysis","volume":"221","author":"Brusselaers","year":"2019","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100877","DOI":"10.1016\/j.currproblcancer.2022.100877","article-title":"The vaginal microbiome: A complex milieu affecting risk of human papillomavirus persistence and cervical cancer","volume":"46","author":"Alimena","year":"2022","journal-title":"Curr. Probl. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1097\/QAD.0b013e3283021a37","article-title":"Bacterial vaginosis and HIV acquisition: A meta-analysis of published studies","volume":"22","author":"Atashili","year":"2008","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1097\/QAD.0000000000000432","article-title":"The vaginal microbiota and susceptibility to HIV","volume":"28","author":"Buve","year":"2014","journal-title":"AIDS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e192","DOI":"10.1097\/OLQ.0000000000001537","article-title":"Bacterial Vaginosis and Its Association With Incident Trichomonas vaginalis Infections: A Systematic Review and Meta-Analysis","volume":"48","author":"Goldstein","year":"2021","journal-title":"Sex. Transm. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: Global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jri.2009.08.007","article-title":"Impact of T. vaginalis infection on innate immune responses and reproductive outcome","volume":"83","author":"Fichorova","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/OLQ.0000000000000134","article-title":"Trichomonas vaginalis as a Cause of Perinatal Morbidity: A Systematic Review and Meta-Analysis","volume":"41","author":"Silver","year":"2014","journal-title":"Sex. Transm. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/1471-0528.16774","article-title":"Trichomoniasis and adverse birth outcomes: A systematic review and meta-analysis","volume":"128","author":"Jones","year":"2021","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_23","first-page":"CD000220","article-title":"Interventions for trichomoniasis in pregnancy","volume":"2011","author":"Azhar","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fichorova, R.N., Lee, Y., Yamamoto, H.S., Takagi, Y., Hayes, G.R., Goodman, R.P., Chepa-Lotrea, X., Buck, O.R., Murray, R., and Kula, T. (2012). Endobiont viruses sensed by the human host\u2014Beyond conventional antiparasitic therapy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048418"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103820","DOI":"10.1016\/j.micpath.2019.103820","article-title":"Vaginal dysbiotic bacteria act as pathobionts of the protozoal pathogen Trichomonas vaginalis","volume":"138","author":"Hinderfeld","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/OLQ.0b013e3182631c79","article-title":"Association between Trichomonas vaginalis and vaginal bacterial community composition among reproductive-age women","volume":"39","author":"Brotman","year":"2012","journal-title":"Sex. Transm. Dis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6163","DOI":"10.1038\/sj.onc.1209909","article-title":"Principles and effects of microRNA-mediated post-transcriptional gene regulation","volume":"25","author":"Engels","year":"2006","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/ng865","article-title":"Micro RNAs are complementary to 3\u2032 UTR sequence motifs that mediate negative post-transcriptional regulation","volume":"30","author":"Lai","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Woith, E., Fuhrmann, G., and Melzig, M.F. (2019). Extracellular Vesicles\u2014Connecting Kingdoms. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225695"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25040","DOI":"10.3402\/jev.v3.25040","article-title":"Extracellular vesicles in parasitic diseases","volume":"3","author":"Marcilla","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Twu, O., de Miguel, N., Lustig, G., Stevens, G.C., Vashisht, A.A., Wohlschlegel, J.A., and Johnson, P.J. (2013). Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host:parasite interactions. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003482"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1007\/s00018-017-2726-3","article-title":"Membrane-shed vesicles from the parasite Trichomonas vaginalis: Characterization and their association with cell interaction","volume":"75","author":"Nievas","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21354","DOI":"10.1073\/pnas.1912356116","article-title":"Trichomonas vaginalis extracellular vesicles are internalized by host cells using proteoglycans and caveolin-dependent endocytosis","volume":"116","author":"Rai","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591172","DOI":"10.3389\/fcimb.2020.591172","article-title":"The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From Trichomonasvirus in an Isogenic Host Parasite Model","volume":"10","author":"Govender","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1095\/biolreprod57.4.847","article-title":"Generation of papillomavirus-immortalized cell lines from normal human ectocervical, endocervical, and vaginal epithelium that maintain expression of tissue-specific differentiation proteins","volume":"57","author":"Fichorova","year":"1997","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00168-00111","DOI":"10.1128\/mBio.00168-11","article-title":"Novel vaginal microflora colonization model providing new insight into microbicide mechanism of action","volume":"2","author":"Fichorova","year":"2011","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1128\/IAI.00631-06","article-title":"Trichomonas vaginalis lipophosphoglycan triggers a selective upregulation of cytokines by human female reproductive tract epithelial cells","volume":"74","author":"Fichorova","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1074\/jbc.M115.651497","article-title":"Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity","volume":"291","author":"Fichorova","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.carres.2015.11.001","article-title":"Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis","volume":"419","author":"Heiss","year":"2016","journal-title":"Carbohydr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10719-008-9157-1","article-title":"Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function","volume":"26","author":"Singh","year":"2009","journal-title":"Glycoconj. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1136\/sextrans-2013-051052","article-title":"The villain team-up or how Trichomonas vaginalis and bacterial vaginosis alter innate immunity in concert","volume":"89","author":"Fichorova","year":"2013","journal-title":"Sex. Transm. Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1177\/1099800420987888","article-title":"Elevated Intestinal Inflammation in Preterm Infants With Signs and Symptoms of Gastroesophageal Reflux Disease","volume":"23","author":"Shelly","year":"2021","journal-title":"Biol. Res. Nurs."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1128\/JVI.00220-11","article-title":"Clinical isolates of Trichomonas vaginalis concurrently infected by strains of up to four Trichomonasvirus species (Family Totiviridae)","volume":"85","author":"Goodman","year":"2011","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00705-010-0832-8","article-title":"Trichomonasvirus: A new genus of protozoan viruses in the family Totiviridae","volume":"156","author":"Goodman","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e00056-13","DOI":"10.1128\/mBio.00056-13","article-title":"Structure of a protozoan virus from the human genitourinary parasite Trichomonas vaginalis","volume":"4","author":"Parent","year":"2013","journal-title":"mBio"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1128\/aem.53.12.2779-2784.1987","article-title":"Qualitative assessment of vaginal microflora during use of tampons of various compositions","volume":"53","author":"Onderdonk","year":"1987","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_48","first-page":"19703","article-title":"Effects of feminine hygiene products on the vaginal mucosal biome","volume":"24","author":"Fashemi","year":"2013","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649940","DOI":"10.3389\/fcimb.2021.649940","article-title":"Protozoan-Viral-Bacterial Co-Infections Alter Galectin Levels and Associated Immunity Mediators in the Female Genital Tract","volume":"11","author":"Fichorova","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1093\/annonc\/mdx210","article-title":"The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1\/PD-L1 blockade","volume":"28","author":"Foy","year":"2017","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.1158\/1078-0432.CCR-15-2900","article-title":"An Expression Signature as an Aid to the Histologic Classification of Non-Small Cell Lung Cancer","volume":"22","author":"Girard","year":"2016","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.2217\/epi-2016-0031","article-title":"miRNAs differentially expressed by next-generation sequencing in cord blood buffy coat samples of boys and girls","volume":"8","author":"Lizarraga","year":"2016","journal-title":"Epigenomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1212\/WNL.0000000000004844","article-title":"MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study","volume":"90","author":"Reed","year":"2018","journal-title":"Neurology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2337\/db17-1207","article-title":"Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes","volume":"67","author":"Satake","year":"2018","journal-title":"Diabetes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S1470-2045(17)30065-7","article-title":"Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial","volume":"18","author":"Sharma","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1101\/gr.6678707","article-title":"Systematic condition-dependent annotation of metabolic genes","volume":"17","author":"Shlomi","year":"2007","journal-title":"Genome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bardou, P., Mariette, J., Escudi\u00e9, F., Djemiel, C., and Klopp, C. (2014). jvenn: An interactive Venn diagram viewer. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-293"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sticht, C., De La Torre, C., Parveen, A., and Gretz, N. (2018). miRWalk: An online resource for prediction of microRNA binding sites. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206239"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.pharmthera.2013.01.016","article-title":"Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review","volume":"138","author":"Csermely","year":"2013","journal-title":"Pharm. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3389\/fimmu.2018.00738","article-title":"Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression","volume":"9","author":"Willms","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2091369","DOI":"10.1080\/19490976.2022.2091369","article-title":"Intestinal accumulation of microbiota-produced succinate caused by loss of microRNAs leads to diarrhea in weanling piglets","volume":"14","author":"Zhou","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.resmic.2017.03.005","article-title":"Trichomonas vaginalis infection in symbiosis with Trichomonasvirus and Mycoplasma","volume":"168","author":"Fichorova","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"132ra152","DOI":"10.1126\/scitranslmed.3003605","article-title":"Temporal dynamics of the human vaginal microbiota","volume":"4","author":"Gajer","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1038\/s41467-019-13468-9","article-title":"Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues","volume":"10","author":"Vanpouille","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e00175-21","DOI":"10.1128\/mSystems.00175-21","article-title":"A MicroRNA Gene Panel Predicts the Vaginal Microbiota Composition","volume":"6","author":"Cheng","year":"2021","journal-title":"mSystems"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nrg1328","article-title":"Micromanagers of gene expression: The potentially widespread influence of metazoan microRNAs","volume":"5","author":"Bartel","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"758","DOI":"10.3390\/ijms15010758","article-title":"Increased Exosomal MicroRNA-21 and MicroRNA-146a Levels in the Cervicovaginal Lavage Specimens of Patients with Cervical Cancer","volume":"15","author":"Liu","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.31557\/APJCP.2021.22.4.1271","article-title":"Pap Smear miR-92a-5p and miR-155-5p as potential diagnostic biomarkers of squamous intraepithelial cervical cancer","volume":"22","author":"Azimi","year":"2021","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/dc.23388","article-title":"Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women","volume":"44","author":"Derchain","year":"2016","journal-title":"Diagn. Cytopathol."},{"key":"ref_74","first-page":"1","article-title":"Vaginosis-associated bacteria and its association with HPV infection","volume":"152","author":"Bandala","year":"2019","journal-title":"Med. Clin."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhang, A. (2009). Protein Interaction Networks: Computational Analysis, Cambridge University Press.","DOI":"10.1017\/CBO9780511626593"},{"key":"ref_76","first-page":"5676","article-title":"The interplay between immune system and microbiota in gynecological diseases: A narrative review","volume":"24","author":"Villa","year":"2020","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Capece, A., Vasieva, O., Meher, S., Alfirevic, Z., and Alfirevic, A. (2014). Pathway Analysis of Genetic Factors Associated with Spontaneous Preterm Birth and Pre-Labor Preterm Rupture of Membranes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108578"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"925","DOI":"10.2217\/epi.16.9","article-title":"Adverse maternal exposures, methylation of glucocorticoid-related genes and perinatal outcomes: A systematic review","volume":"8","author":"Nagarajan","year":"2016","journal-title":"Epigenomics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/15592294.2021.1980691","article-title":"Perinatal stress and methylation of the NR3C1 gene in newborns: Systematic review","volume":"17","author":"Chalfun","year":"2022","journal-title":"Epigenetics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"839005","DOI":"10.3389\/fendo.2022.839005","article-title":"Role of estrogen receptors in health and disease","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cyto.2015.01.007","article-title":"Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity","volume":"72","author":"Shivers","year":"2015","journal-title":"Cytokine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.jaci.2013.09.007","article-title":"The biology of the glucocorticoid receptor: New signaling mechanisms in health and disease","volume":"132","author":"Oakley","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.molcel.2005.03.025","article-title":"Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes","volume":"18","author":"Lu","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41398-022-02160-0","article-title":"Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: When timing matters","volume":"12","author":"Nazzari","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3389\/fpsyt.2019.00220","article-title":"Stressful Newborn Memories: Pre-Conceptual, In Utero, and Postnatal Events","volume":"10","author":"Papadopoulou","year":"2019","journal-title":"Front. Psychiatry"},{"key":"ref_87","first-page":"129","article-title":"The IGF axis and placental function. a mini review","volume":"69","author":"Forbes","year":"2008","journal-title":"Horm. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.3389\/fimmu.2019.03017","article-title":"Steroids, Pregnancy and Fetal Development","volume":"10","author":"Solano","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-020-01258-7","article-title":"Targeting STAT3 in Cancer Immunotherapy","volume":"19","author":"Zou","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3892\/ol.2020.12316","article-title":"Circulating exosomal miR-125a-5p as a novel biomarker for cervical cancer","volume":"21","author":"Lv","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1210\/en.2014-1101","article-title":"ESR1 and ESR2 differentially regulate daily and circadian activity rhythms in female mice","volume":"155","author":"Royston","year":"2014","journal-title":"Endocrinology"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Xiao, L., Chang, A.K., Zang, M.X., Bi, H., Li, S., Wang, M., Xing, X., and Wu, H. (2014). Induction of the CLOCK gene by E2-ER\u03b1 signaling promotes the proliferation of breast cancer cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095878"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1128\/CMR.14.3.476-488.2001","article-title":"Sex-associated hormones and immunity to protozoan parasites","volume":"14","author":"Roberts","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/3\/551\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:38:33Z","timestamp":1760121513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/3\/551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":95,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["microorganisms11030551"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11030551","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}