{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:22:02Z","timestamp":1780503722919,"version":"3.54.1"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["212250-3210-21205-01-15"],"award-info":[{"award-number":["212250-3210-21205-01-15"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB-242162"],"award-info":[{"award-number":["CB-242162"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal\u2013fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 \u00d7 105 CFU\/mL). Amnion and choriodecidual AMP tissue levels and TNF-\u03b1 and IL-1\u03b2 secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2\u20134 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8\u201324 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.<\/jats:p>","DOI":"10.3390\/ijms23062994","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"2994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-9695","authenticated-orcid":false,"given":"Andrea","family":"Olmos-Ortiz","sequence":"first","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra","family":"Hern\u00e1ndez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-3629","authenticated-orcid":false,"given":"Pilar","family":"Flores-Espinosa","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Sedano","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addy Cecilia","family":"Helguera-Repetto","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Villavicencio-Carrisoza","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Yolotzin","family":"Valdespino-Vazquez","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda Patol\u00f3gica, INPer, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-6098","authenticated-orcid":false,"given":"Arturo","family":"Flores-Pliego","sequence":"additional","affiliation":[{"name":"Departamento de Inmunobioqu\u00edmica, Instituto Nacional de Perinatolog\u00eda (INPer), Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Irles","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Desarrollo Celular, INPer, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Rivas-Santiago","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica IMSS Zacatecas, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa Romelia","family":"Moreno-Verduzco","sequence":"additional","affiliation":[{"name":"Subdirecci\u00f3n de Auxiliares de Diagn\u00f3stico, INPer, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-4222","authenticated-orcid":false,"given":"Lorenza","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-2932","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Zaga-Clavellina","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Desarrollo Celular, INPer, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1016\/S2214-109X(18)30451-0","article-title":"Global, Regional, and National Estimates of Levels of Preterm Birth in 2014: A Systematic Review and Modelling Analysis","volume":"7","author":"Chawanpaiboon","year":"2019","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s41372-019-0563-y","article-title":"Preterm Birth and Mortality in Adulthood: A Systematic Review","volume":"40","author":"Crump","year":"2020","journal-title":"J. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/1098-0997(2000)8:5<220::AID-IDOG1022>3.0.CO;2-I","article-title":"Intrauterine Infection and Spontaneous Midgestation Abortion: Is the Spectrum of Microorganisms Similar to That in Preterm Labor?","volume":"8","author":"McDonald","year":"2000","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"S\u00e1ez-L\u00f3pez, E., Guiral, E., Fern\u00e1ndez-Orth, D., Villanueva, S., Gonc\u00e9, A., L\u00f3pez, M., Teixid\u00f3, I., Pericot, A., Figueras, F., and Palacio, M. (2016). Vaginal versus Obstetric Infection Escherichia coli Isolates among Pregnant Women: Antimicrobial Resistance and Genetic Virulence Profile. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146531"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/jog.13687","article-title":"Maternal and Perinatal Complications in Pregnant Women with Urinary Tract Infection Caused by Escherichia coli","volume":"44","year":"2018","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1213\/ANE.0000000000003709","article-title":"Risk Factors, Etiologies, and Screening Tools for Sepsis in Pregnant Women: A Multicenter Case-Control Study","volume":"129","author":"Bauer","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_7","first-page":"287","article-title":"Pathogens in Preterm Prelabour Rupture of Membranes and Erythromycin for Antibiotic Prophylaxis: A Retrospective Analysis","volume":"25","author":"Li","year":"2019","journal-title":"Hong Kong Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1097\/AOG.0000000000003515","article-title":"Stillbirth Associated with Infection in a Diverse, U.S. Cohort","volume":"134","author":"Page","year":"2019","journal-title":"Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.resmic.2017.02.002","article-title":"The Role of Escherichia coli in Reproductive Health: State of the Art","volume":"168","author":"Cools","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/infdis\/157.1.113","article-title":"Intraamniotic Infection in Low-Birth-Weight Infants","volume":"157","author":"Sperling","year":"1988","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/infdis\/145.1.1","article-title":"Quantitative Bacteriology of Amniotic Fluid from Women with Clinical Intraamniotic Infection at Term","volume":"145","author":"Gibbs","year":"1982","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/01443615.2020.1789955","article-title":"Relationship between Histologic Chorioamnionitis and Genital Tract Cultures in Pre Term Labour","volume":"41","author":"Thakur","year":"2021","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1515\/jpm-2019-0297","article-title":"Evidence That Intra-Amniotic Infections Are Often the Result of an Ascending Invasion\u2014A Molecular Microbiological Study","volume":"47","author":"Romero","year":"2019","journal-title":"J. Perinat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1530\/REP-10-0537","article-title":"Antimicrobial Peptides and Pregnancy","volume":"141","author":"Frew","year":"2011","journal-title":"Reproduction"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1111\/apa.12700","article-title":"A Review of the Innate Immune Defence of the Human Foetus and Newborn, with the Emphasis on Antimicrobial Peptides","volume":"103","author":"Gudmundsson","year":"2014","journal-title":"Acta Paediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"691522","DOI":"10.3389\/fbioe.2021.691522","article-title":"Antimicrobial Activity of Human Fetal Membranes: From Biological Function to Clinical Use","volume":"9","author":"Ramuta","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Olmos-Ortiz, A., Flores-Espinosa, P., Mancilla-Herrera, I., Vega-S\u00e1nchez, R., D\u00edaz, L., and Zaga-Clavellina, V. (2019). Innate Immune Cells and Toll-like Receptor\u2013Dependent Responses at the Maternal\u2013Fetal Interface. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153654"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/humupd\/dmu065","article-title":"Antimicrobial Peptides in the Female Reproductive Tract: A Critical Component of the Mucosal Immune Barrier with Physiological and Clinical Implications","volume":"21","author":"Yarbrough","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Son, G.H., Lee, J.J., Kim, Y., and Lee, K.Y. (2021). The Role of Antimicrobial Peptides in Preterm Birth. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168905"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0301-2115(00)00345-6","article-title":"Antibacterial Properties of Human Amnion and Chorion in Vitro","volume":"94","author":"Kjaergaard","year":"2001","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.placenta.2006.01.006","article-title":"Expression of Natural Antimicrobials by Human Placenta and Fetal Membranes","volume":"28","author":"King","year":"2007","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255.e1","DOI":"10.1016\/j.ajog.2006.10.908","article-title":"Natural Antimicrobial Production by the Amnion","volume":"196","author":"Stock","year":"2007","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1067\/mob.2002.123034","article-title":"Antimicrobial Factors in the Cervical Mucus Plug","volume":"187","author":"Hein","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-0897.1997.tb00511.x","article-title":"Detection of Human Defensins in the Placenta","volume":"38","author":"Svinarich","year":"1997","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3109\/14767050902994796","article-title":"Differential Expression Pattern of Genes Encoding for Anti-Microbial Peptides in the Fetal Membranes of Patients with Spontaneous Preterm Labor and Intact Membranes and Those with Preterm Prelabor Rupture of the Membranes","volume":"22","author":"Erez","year":"2009","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1203\/00006450-200302000-00003","article-title":"Antimicrobial Polypeptides of Human Vernix Caseosa and Amniotic Fluid: Implications for Newborn Innate Defense","volume":"53","author":"Yoshio","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1128\/AAC.49.1.269-275.2005","article-title":"Antibacterial Activity and Specificity of Six Human \u03b1-Defensins","volume":"49","author":"Ericksen","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1177\/1933719109341998","article-title":"Elafin (SKALP\/Trappin-2\/Proteinase Inhibitor-3) Is Produced by the Cervix in Pregnancy and Cervicovaginal Levels Are Diminished in Bacterial Vaginosis","volume":"16","author":"Stock","year":"2009","journal-title":"Reprod. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.3389\/fimmu.2019.02553","article-title":"The Antimicrobial and Immunomodulatory Function of RNase 7 in Skin","volume":"10","author":"Rademacher","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1128\/AAC.00246-06","article-title":"Identification of RNase 8 as a Novel Human Antimicrobial Protein","volume":"50","author":"Rudolph","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"739","DOI":"10.2174\/1566524013363258","article-title":"Mammalian Secreted Phospholipases A2 and Their Pathophysiolo-Gical Significance in Inflammatory Diseases","volume":"1","author":"Touqui","year":"2005","journal-title":"Curr. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cytogfr.2016.01.002","article-title":"S100A7: A RAMPing up AMP Molecule in Psoriasis","volume":"32","author":"Skarmoutsou","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/biof.1225","article-title":"Unique Features of Human Cathelicidin LL-37","volume":"41","author":"Bandurska","year":"2015","journal-title":"BioFactors"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1477-7827-1-116","article-title":"Innate Immune Defences in the Human Endometrium","volume":"1","author":"King","year":"2003","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jsbmb.2016.05.017","article-title":"Evidence of Sexual Dimorphism in Placental Vitamin D Metabolism: Testosterone Inhibits Calcitriol-Dependent Cathelicidin Expression","volume":"163","author":"Olivares","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/1477-7827-8-146","article-title":"Tissue-Specific Human Beta-Defensins (HBD)1, HBD2, and HBD3 Secretion from Human Extra-Placental Membranes Stimulated with Escherichia coli","volume":"8","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_37","first-page":"4241","article-title":"The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation","volume":"12","author":"Ramuta","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/0002-9378(84)90534-9","article-title":"Bacterial Attachment to the Chorioamniotic Membranes","volume":"148","author":"Galask","year":"1984","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0002-9378(13)70307-7","article-title":"Permeation of Human Chorioamniotic Membranes by Escherichia coli in Vitro","volume":"170","author":"Gyr","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.placenta.2011.08.004","article-title":"Contribution of Different Placental Cells to the Expression and Stimulation of Antimicrobial Proteins (AMPs)","volume":"32","author":"Klaffenbach","year":"2011","journal-title":"Placenta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17022","DOI":"10.1038\/s41598-017-17210-7","article-title":"Induction of Antimicrobial Peptides Secretion by IL-1\u03b2 Enhances Human Amniotic Membrane for Regenerative Medicine","volume":"7","author":"Tehrani","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jri.2017.09.004","article-title":"Selective Immuno-Modulatory Effect of Prolactin upon pro-Inflammatory Response in Human Fetal Membranes","volume":"123","year":"2017","journal-title":"J. Reprod. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/1933719109348025","article-title":"Choriodecidual Inflammation: A Harbinger of the Preterm Labor Syndrome","volume":"17","author":"Grigsby","year":"2010","journal-title":"Reprod. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/1933719107310992","article-title":"Pretreatment with Toll-like Receptor 4 Antagonist Inhibits Lipopolysaccharide-Induced Preterm Uterine Contractility, Cytokines, and Prostaglandins in Rhesus Monkeys","volume":"15","author":"Persing","year":"2008","journal-title":"Reprod. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/aji.12163","article-title":"Progesterone Elicits an Inhibitory Effect upon LPS-Induced Innate Immune Response in Pre-Labor Human Amniotic Epithelium","volume":"71","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1477-7827-7-117","article-title":"Tissue-Specific Cytokine Release from Human Extra-Placental Membranes Stimulated by Lipopolysaccharide in a Two-Compartment Tissue Culture System","volume":"7","author":"Thiex","year":"2009","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1095\/biolreprod.104.028621","article-title":"Secretions of Interleukin-1\u03b2 and Tumor Necrosis Factor \u03b1 by Whole Fetal Membranes Depend on Initial Interactions of Amnion or Choriodecidua with Lipopolysaccharides or Group B Streptococci","volume":"71","author":"Zaga","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00404-009-1155-4","article-title":"The Role of Human Beta Defensins 2 and 3 in the Second Trimester Amniotic Fluid in Predicting Preterm Labor and Premature Rupture of Membranes","volume":"281","author":"Iavazzo","year":"2010","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e13031","DOI":"10.1111\/aji.13031","article-title":"Human \u03b2-Defensin-1: A Natural Antimicrobial Peptide Present in Amniotic Fluid That Is Increased in Spontaneous Preterm Labor with Intra-Amniotic Infection","volume":"80","author":"Varrey","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/jmf.13.1.2.21","article-title":"Antimicrobial Peptides in Amniotic Fluid: Defensins, Calprotectin and Bacterial\/Permeability-Increasing Protein in Patients with Microbial Invasion of the Amniotic Cavity, Intra-Amniotic Inflammation, Preterm Labor and Premature Rupture of Membranes","volume":"13","author":"Espinoza","year":"2003","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ijgo.2016.01.007","article-title":"Diagnostic Value of Amniotic Fluid Inflammatory Biomarkers for Subclinical Chorioamnionitis","volume":"134","author":"Liu","year":"2016","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.ajog.2004.03.081","article-title":"The Novel Antimicrobial Peptide \u03923-Defensin Is Produced by the Amnion: A Possible Role of the Fetal Membranes in Innate Immunity of the Amniotic Cavity","volume":"191","author":"Buhimschi","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00011-007-0633-z","article-title":"Increased Production of \u03b2-Defensin 3 (HBD-3) by Human Amniotic Epithelial Cells (HAEC) after Activation of Toll-like Receptor 4 in Chorioamnionitis","volume":"57","author":"Szukiewicz","year":"2008","journal-title":"Inflamm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"358","DOI":"10.3109\/14767058.2011.578695","article-title":"Evidence of in Vitro Differential Secretion of Human Beta-Defensins-1, -2, and -3 after Selective Exposure to Streptococcus agalactiae in Human Fetal Membranes","volume":"25","year":"2012","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1600-0897.2011.01054.x","article-title":"In Vitro Secretion Profile of Pro-Inflammatory Cytokines IL-1\u03b2, TNF-\u03b1, IL-6, and of Human Beta-Defensins (HBD)-1, HBD-2, and HBD-3 from Human Chorioamniotic Membranes after Selective Stimulation with Gardnerella vaginalis","volume":"67","author":"Martha","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jsbmb.2014.07.012","article-title":"IL-10 Inhibits While Calcitriol Reestablishes Placental Antimicrobial Peptides Gene Expression","volume":"148","author":"Barrera","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e12841","DOI":"10.1111\/aji.12841","article-title":"Lipopolysaccharide and cAMP Modify Placental Calcitriol Biosynthesis Reducing Antimicrobial Peptides Gene Expression","volume":"79","author":"Avila","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jdermsci.2005.03.014","article-title":"Synergistic Effect of Antibacterial Agents Human \u03b2-Defensins, Cathelicidin LL-37 and Lysozyme against Staphylococcus aureus and Escherichia coli","volume":"40","author":"Chen","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vanzolini, T., Bruschi, M., Rinaldi, A.C., Magnani, M., and Fraternale, A. (2022). Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010545"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Luo, Y., and Song, Y. (2021). Mechanism of Antimicrobial Peptides: Antimicrobial, Anti-Inflammatory and Antibiofilm Activities. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111401"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"ii17","DOI":"10.1136\/ard.62.suppl_2.ii17","article-title":"Roles of Antimicrobial Peptides Such as Defensins in Innate and Adaptive Immunity","volume":"62","author":"Oppenheim","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, G. (2010). Antimicrobial Peptides: Discovery, Design, and Novel Therapeutic Strategies, CABI.","DOI":"10.1079\/9781845936570.0000"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fmedt.2021.640981","article-title":"Developing Antimicrobial Synergy With AMPs","volume":"3","author":"Duong","year":"2021","journal-title":"Front. Med. Technol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Hao, W., Wang, X., Ouyang, J., Deng, X., Yu, H., and Wang, Y. (2022). Antimicrobial Peptides, Conventional Antibiotics, and Their Synergistic Utility for the Treatment of Drug-Resistant Infections. Med. Res. Rev.","DOI":"10.1002\/med.21879"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.peptides.2012.08.024","article-title":"Antimicrobial Activity of Human \u03b2-Defensin 4 Analogs: Insights into the Role of Disulfide Linkages in Modulating Activity","volume":"38","author":"Sharma","year":"2012","journal-title":"Peptides"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/1574-6968.12242","article-title":"Human-\u03b2-Defensins-1-3 and Analogs Do Not Require Proton Motive Force for Antibacterial Activity against Escherichia coli","volume":"348","author":"Krishnakumari","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1128\/AEM.66.10.4555-4558.2000","article-title":"Rapid and Simple Determination of the Escherichia coli Phylogenetic Group","volume":"66","author":"Clermont","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/315217","article-title":"Extended Virulence Genotypes of Escherichia coli Strains from Patients with Urosepsis in Relation to Phylogeny and Host Compromise","volume":"181","author":"Johnson","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_69","unstructured":"Scottish Intercollegiate Guidelines Network (SIGN) (2012). Management of Suspected Bacterial Urinary Tract Infection in Adults, Scottish Intercollegiate Guidelines Network (SIGN)."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/archinte.1957.00260110025004","article-title":"Bacteriuria and the Diagnosis of Infections of the Urinary Tract: With Observations on the Use of Methionine as a Urinary Antiseptic","volume":"100","author":"Kass","year":"1957","journal-title":"AMA Arch. Intern. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Becerra, S.C., Roy, D.C., Sanchez, C.J., Christy, R.J., and Burmeister, D.M. (2016). An Optimized Staining Technique for the Detection of Gram Positive and Gram Negative Bacteria within Tissue. BMC Res. Notes, 9.","DOI":"10.1186\/s13104-016-1902-0"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Segnani, C., Ippolito, C., Antonioli, L., Pellegrini, C., Blandizzi, C., Dolfi, A., and Bernardini, N. (2015). Histochemical Detection of Collagen Fibers by Sirius Red\/Fast Green Is More Sensitive than van Gieson or Sirius Red Alone in Normal and Inflamed Rat Colon. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144630"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2994\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:21Z","timestamp":1760135661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":72,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23062994"],"URL":"https:\/\/doi.org\/10.3390\/ijms23062994","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]}}}