- Title
- Effect of maternal asthma during pregnancy on aspects of placental immune function
- Creator
- Scott, Naomi
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2012
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- In the presence of maternal asthma, reduced placental blood flow, decreased cortisol metabolism, and reductions in fetal growth have been reported in response to maternal asthma and asthma exacerbations. The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in aspects of placental immune function. The influence of maternal asthma and it’s severity, maternal cigarette use, and fetal sex on placental cytokine mRNA expression was examined in a prospective cohort study of pregnant women with and without asthma. Placental expression of TNF-α, IL-1β, IL-6, IL-8 and IL-5 mRNA were all increased significantly in placenta of female fetuses whose mothers had mild asthma, but no changes were observed in placenta of male fetuses. The pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placenta from males. Multivariate analysis indicated the strongest predictor of both cytokine mRNA expression in the placenta and birth weight was fetal cortisol, but only in females. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, moderate-severe asthma, or male sex. These data suggested that placental basal cytokine mRNA expression is sex specifically regulated in pregnancies complicated by asthma, and interestingly these changes are more prevalent in mild rather than severe asthma. The placental cytokine response in vitro was examined in an additional prospective cohort study of women with asthma, and controls. Placentae were collected immediately following delivery, and placental explants were exposed to LPS immune stimulation, in the presence and absence of glucocorticoids in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPKinase protein were measured. Placentae from pregnancies complicated by maternal asthma had a more rapid response to LPS than control placenta, regardless of fetal sex, with early production of the cytokines IL-6, IL-8 and IL-10, but did not sustain the enhanced cytokine response by 24 h relative to a control population. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex, and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. This data demonstrates that the placentae from pregnancies complicated by maternal asthma differ from control placentae in relation to the timing of the response to LPS stimulation, and the regulation of the response by cortisol. This is the first study to examine the impact of maternal asthma during pregnancy on placental inflammatory pathways. The data has identified that asthma during pregnancy alters pro-inflammatory pathways in a sex specific manner. Female placentae readily control pro-inflammatory cytokine expression via the glucocorticoid pathway while male placentae appear glucocorticoid resistant. This data suggests that during a pro-inflammatory event such as an asthma exacerbation the female fetus may protect herself from the effects of this stress via cortisol. Males babies may be more at risk of a poor outcome due to an inability to regulate inflammation via cortisol. Placentae from asthmatic pregnancies had an enhanced early cytokine response to LPS stimulation, suggesting previous exposure to inflammatory disease alters responsiveness of cytokines in the placenta to an LPS stimulation.
- Subject
- asthma; pregnancy; placental immune function; maternal cigarette use
- Identifier
- http://hdl.handle.net/1959.13/934241
- Identifier
- uon:11811
- Rights
- Copyright 2012 Naomi Scott
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT02 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download |