Research Doctorate - Doctor of Philosophy (PhD) / Maternal asthma is associated with low birth weight, a risk factor for disease in adult life. To determine the mechanisms involved, the relationships between mother, placenta and fetus were examined in asthmatic and non-asthmatic pregnancies. Maternal asthma and its treatment (no glucocorticoid or glucocorticoid) was monitored throughout pregnancy. Fetal growth was examined during gestation, and at birth, neonatal size and sex were determined. Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) enzyme activity and umbilical vein plasma cortisol and estriol concentrations were measured. Placental cytokine, growth factor and glucocorticoid receptor (GR) mRNA were determined using quantitative RT-PCR. Birth weight of female neonates in the no glucocorticoid asthmatic group only, was significantly reduced compared to females of the non-asthmatic group. Male neonates were unaffected by asthma or its treatment. Asthmatic women pregnant with a female fetus showed a significant increase in circulating monocytes and glucocorticoid treatment as pregnancy progressed, while those pregnant with a male fetus did not, suggesting that maternal asthma worsens in the presence of a female fetus. 11beta-HSD2 activity was significantly reduced in placentae from female neonates of the no glucocorticoid group compared to other female neonates and was associated with a trend towards higher plasma cortisol, reduced fetal adrenal activity demonstrated by lower cord blood estriol, reduced placental GR expression, no alteration in placental or fetal insulin-like growth factors or their binding proteins and a significantly increased Th2:Th1 cytokine mRNA ratio, which was inversely correlated with 11beta-HSD2 activity in all females. Reduced placental 11beta-HSD2 activity may be an important component leading to decreased female fetal growth in pregnancies complicated by asthma. This study provides strong evidence for a fetal sex-specific effect on the maternal immune system which can have adverse effects on the female fetus. The female fetus alters maternal inflammatory pathways, which when not controlled by the use of inhaled glucocorticoids results in reduced placental 11beta-HSD2 activity, contributing to suppressed fetal adrenal function and a late gestation decrease in female fetal growth.
| Identifer | oai:union.ndltd.org:ADTP/222125 |
| Date | January 2004 |
| Creators | Murphy, Vanessa Evonne |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright 2004 Vanessa Evonne Murphy |
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