title: Interaction between pathogenic bacteria and intrauterine leukocytes triggers alternative molecular signaling cascades leading to labor in women.
abstract: Increased risk of preterm labor has been linked to cervicovaginal infection with Ureaplasma urealyticum and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with U. urealyticum induced a highly significant secretion of interleukin-1β (IL-1β) and prostaglandin E(2) (PGE(2)) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-α, whereas U. urealyticum stimulates the secretion of PGE(2), probably via IL-1β, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.
authors.affiliation: Research Direction, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Estrada-Gutierrez
authors.forename: Nardhy
authors.initials: N
authors.lastname: Gomez-Lopez
authors.forename: Veronica
authors.initials: V
authors.lastname: Zaga-Clavellina
authors.forename: Silvia
authors.initials: S
authors.lastname: Giono-Cerezo
authors.forename: Aurora
authors.initials: A
authors.lastname: Espejel-Nuñez
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Gonzalez-Jimenez
authors.forename: Salvador
authors.initials: S
authors.lastname: Espino y Sosa
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
authors.forename: Felipe
authors.initials: F
authors.lastname: Vadillo-Ortega
mesh_terms: D000650:Amnion / Q000276:immunology* / Q000378:metabolism; D002823:Chorion / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000276:immunology*; D009924:Organ Culture Techniques; D010920:Placenta / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D015398:Signal Transduction; D013292:Streptococcus agalactiae / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016990:Ureaplasma urealyticum / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
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