Clarithromycin prevents preterm birth and neonatal mortality by dampening alarmin-induced maternal–fetal infammation in mice

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dc.article.number503
dc.contributor.authorGalaz, José
dc.contributor.authorRomero, Roberto
dc.contributor.authorArenas-Hernandez, Marcia
dc.contributor.authorFarías Jofré, Marcelo Enrique
dc.contributor.authorMotomura, Kenichiro
dc.contributor.authorLiu, Zhenjie
dc.contributor.authorKawahara, Naoki
dc.contributor.authorDemery-Poulos, Catherine
dc.contributor.authorLiu, Tzu N.
dc.contributor.authorPadron, Justin
dc.contributor.authorPanaitescu, Bogdan
dc.contributor.authorGomez-Lopez, Nardhy
dc.date.accessioned2022-07-04T13:28:20Z
dc.date.available2022-07-04T13:28:20Z
dc.date.issued2022
dc.date.updated2022-06-26T00:03:38Z
dc.description.abstractBackground: One of every four preterm neonates is born to a woman with sterile intra-amniotic inflammation (inflammatory process induced by alarmins); yet, this clinical condition still lacks treatment. Herein, we utilized an established murine model of sterile intra-amniotic inflammation induced by the alarmin high-mobility group box-1 (HMGB1) to evaluate whether treatment with clarithromycin prevents preterm birth and adverse neonatal outcomes by dampening maternal and fetal inflammatory responses. Methods: Pregnant mice were intra-amniotically injected with HMGB1 under ultrasound guidance and treated with clarithromycin or vehicle control, and pregnancy and neonatal outcomes were recorded (n = 15 dams each). Additionally, amniotic fluid, placenta, uterine decidua, cervix, and fetal tissues were collected prior to preterm birth for determination of the inflammatory status (n = 7–8 dams each). Results: Clarithromycin extended the gestational length, reduced the rate of preterm birth, and improved neonatal mortality induced by HMGB1. Clarithromycin prevented preterm birth by interfering with the common cascade of parturition as evidenced by dysregulated expression of contractility-associated proteins and inflammatory mediators in the intra-uterine tissues. Notably, clarithromycin improved neonatal survival by dampening inflammation in the placenta as well as in the fetal lung, intestine, liver, and spleen. Conclusions: Clarithromycin prevents preterm birth and improves neonatal survival in an animal model of sterile intra-amniotic inflammation, demonstrating the potential utility of this macrolide for treating women with this clinical condition, which currently lacks a therapeutic intervention.
dc.format.extent18 páginas
dc.fuente.origenAutoarchivo
dc.identifier.citationBMC Pregnancy and Childbirth. 2022 Jun 20;22(1):503
dc.identifier.doi10.1186/s12884-022-04764-2
dc.identifier.urihttps://doi.org/10.1186/s12884-022-04764-2
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/64369
dc.identifier.wosidWOS:000813740300004
dc.information.autorucFacultad de Medicina ; Galaz, José ; 0000-0002-8160-8581 ; 1034327
dc.information.autorucFacultad de Medicina ; Farías Jofré, Marcelo Enrique ; 0000-0003-0473-2295 ; 12286
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final18
dc.pagina.inicio1
dc.revistaBMC Pregnancy and Childbirth
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.subjectAmniotic cavityes_ES
dc.subjectAntibiotices_ES
dc.subjectCytokinees_ES
dc.subjectGene expressiones_ES
dc.subjectHMGB1es_ES
dc.subjectMacrolidees_ES
dc.subjectSterile intra-amniotic infammationes_ES
dc.subject.ddc618.2
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleClarithromycin prevents preterm birth and neonatal mortality by dampening alarmin-induced maternal–fetal infammation in micees_ES
dc.typeartículo
dc.volumen22
sipa.codpersvinculados1034327
sipa.codpersvinculados12286
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