Article

Inflammation of the fetal ovine skin following in utero exposure to Ureaplasma parvum.

School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
Reproductive sciences (Thousand Oaks, Calif.) (Impact Factor: 2.18). 11/2011; 18(11):1128-37. DOI: 10.1177/1933719111408114
Source: PubMed

ABSTRACT There is increasing evidence linking in utero infection and inflammation to preterm birth. Many commensal urogenital tract microorganisms, including the Mycoplasmas and Ureaplasmas, are commonly detected in association with preterm birth. Using an ovine model of sterile fetal inflammation, we demonstrated previously that the fetal skin generates a robust inflammatory response following in utero exposure to lipopolysaccharides from Escherichia coli. The fetal skin's response to colonization of the amniotic fluid by viable microorganisms remains unstudied. We hypothesised that in utero infection with Ureaplasma parvum serovar 3 would induce a proinflammatory response in the fetal skin. We found that (1) cultured fetal keratinocytes (the primary cellular constituent of the epidermis) respond to U. parvum exposure in vitro by increasing the expression of the chemotactant monocyte chemoattractant protein 1 (MCP-1) but not interleukin 1β (IL-1β), IL-6, IL-8, or tumor necrosis factor-α (TNF-α); (2) the fetal skin's response to 7 days of U. parvum exposure is characterized by elevated expression of MCP-1, TNF-α, and IL-10; and (3) the magnitude of inflammatory cytokine/chemokine expression in the fetal skin is dependent on the duration of U parvum exposure. These novel findings provide further support for the role of the fetal skin in the development of fetal inflammation and the preterm birth that may follow.

1 Bookmark
 · 
141 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesised that intraamniotic C. albicans would cause a vigorous, acute fetal inflammatory response.Methods:Sheep carrying singleton pregnancies received single intraamniotic (IA) injections of either saline (control) or 10(7) CFU C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation.Results:Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterised by fetal thrombocytopenia, lymphopenia and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung and the amniotic fluid.Conclusion:Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen which can contribute to adverse pregnancy outcomes.Pediatric Research (2014); doi:10.1038/pr.2014.35.
    Pediatric Research 03/2014; DOI:10.1038/pr.2014.35 · 2.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Preterm birth (PTB) (delivery before 37 weeks' gestation) is a leading cause of neonatal death and disease in industrialized and developing countries alike. Infection (most notably in high-risk deliveries occurring before 28 weeks' gestation) is hypothesized to initiate an intrauterine inflammatory response that plays a key role in the premature initiation of labor as well as a host of the pathologies associated with prematurity. As such, a better understanding of intrauterine inflammation in pregnancy is critical to our understanding of preterm labor and fetal injury, as well as on-going efforts to prevent PTB. Focusing on the fetal innate immune system responses to intrauterine infection, the present paper will review clinical and experimental studies to discuss the capacity for a fetal contribution to the intrauterine inflammation associated with PTB. Evidence from experimental studies to suggest that the fetus has the capacity to elicit a pro-inflammatory response to intrauterine infection is highlighted, with reference to the contribution of the lung, skin, and gastrointestinal tract. The paper will conclude that pathological intrauterine inflammation is a complex process that is modified by multiple factors including time, type of agonist, host genetics, and tissue.
    Frontiers in Immunology 12/2014; 5:574. DOI:10.3389/fimmu.2014.00574
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intra-amniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum (UP) infection in a sheep model of pregnancy.
    Antimicrobial Agents and Chemotherapy 06/2014; 58(9). DOI:10.1128/AAC.03187-14 · 4.45 Impact Factor

Full-text (2 Sources)

Download
42 Downloads
Available from
Jun 2, 2014