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Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
Published on: June 18, 2013
Expression of natural antimicrobials by human placenta and fetal membranes
A E King1, A Paltoo, R W Kelly
1Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. anne.king@utoronto.ca
Abstract:
Preterm birth associated with infection is a major clinical problem. We hypothesized that this condition is associated with altered expression of natural antimicrobial molecules (beta-defensins (HBD), elafin). Therefore, we examined expression of these molecules and their regulation by proinflammatory cytokines in placentae and fetal membranes from term pregnancy. HBD1-3 and elafin were localized by immunohistochemistry in fetal membranes and placenta. Real-time quantitative PCR was used to examine mRNA expression in primary trophoblast cells treated with inflammatory molecules. HBD1-3 and elafin were immunolocalized to placental and chorion trophoblast layers of fetal membranes and placenta. Immunoreactivity was also observed in amnion epithelium and decidua. No differences were noted between samples from women who were not in labour compared to those in active labour. In in vitro cultures of primary trophoblast cells, HBD2 and elafin mRNA expression was upregulated by the proinflammatory cytokine, IL-1beta. These results suggest that the chorion and placental trophoblast layers may be key barriers to the progression of infection in the pregnant uterus. Natural antimicrobial expression may be altered in response to inflammatory mediator expression associated with the onset of labour and/or uterine infection, providing increased protection when the uterus may be particularly susceptible to infection.
Insights
Infection-associated preterm birth may involve changes in natural antimicrobial molecules like beta-defensins (HBD) and elafin. These molecules are present in placental tissues and their expression can be influenced by inflammatory cytokines.
Area of Science:
- Reproductive biology
- Immunology
- Obstetrics
Background:
- Infection-associated preterm birth is a significant clinical challenge.
- Natural antimicrobial molecules, such as beta-defensins (HBD) and elafin, play a role in host defense.
- Their role in the context of pregnancy and preterm birth requires further investigation.
Purpose of the Study:
- To investigate the expression and regulation of HBD and elafin in placental tissues.
- To determine if expression levels differ in term pregnancy, labor, or in response to inflammatory stimuli.
Main Methods:
- Immunohistochemistry was used to localize HBD1-3 and elafin in placental and fetal membrane tissues.
- Real-time quantitative PCR analyzed mRNA expression in primary trophoblast cells stimulated with IL-1beta.
- Tissues were examined from women in term pregnancy, with and without active labor.
Main Results:
- HBD1-3 and elafin were localized to trophoblast layers of the placenta and fetal membranes, as well as amnion epithelium and decidua.
- No significant differences in expression were observed between non-laboring and actively laboring term pregnancy samples.
- In vitro, IL-1beta upregulated HBD2 and elafin mRNA expression in primary trophoblast cells.
Conclusions:
- The chorion and placental trophoblast layers act as crucial barriers against uterine infections.
- Expression of natural antimicrobials may be modulated by inflammatory mediators during labor or infection.
- Altered antimicrobial expression could represent an adaptive response to enhance uterine protection during periods of increased susceptibility to infection.
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