Development of an experimental model of maternal allergic asthma during pregnancy

Vicki L. Clifton, Timothy J. M. Moss, Amy L. Wooldridge, Kathryn L. Gatford, Bahar Liravi, Dasom Kim, Beverly S. Muhlhausler, Janna L. Morrison, Andrew Davies, Robert De Matteo, Megan J. Wallace, Robert Bischof

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We studied the effects of preconceptional allergen sensitisation and repeated airway allergen challenges during pregnancy on maternal immune and airway functions during pregnancy, and maternal, fetal and placental phenotype in late pregnancy in sheep. This protocol induced maternal responses consistent with an allergic asthmatic phenotype. During pregnancy, lung resistance and the eosinophil influx induced by allergen challenges increased progressively in allergic sheep, and in late pregnancy airway smooth muscle content was greater in allergic than control ewes. Effects on fetal growth and development were consistent with those of maternal asthma in humans. Maternal allergic asthma decreased relative fetal weight by 12 , reduced fetal lung expression of surfactant protein B, and altered placental morphology. This provides an animal model in which to identify mechanisms underlying fetal effects of maternal asthma in pregnancy, including fetal physiological responses to exacerbations, and to evaluate responses to clinically used treatments and novel interventions. ABSTRACT: Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 +/- 1 days gestational age (term, approximately 147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12 ) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48 lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.
Original languageEnglish
Pages (from-to)1311 - 1325
Number of pages15
JournalThe Journal of Physiology
Volume594
Issue number5
DOIs
Publication statusPublished - Mar 2016

Cite this

Clifton, V. L., Moss, T. J. M., Wooldridge, A. L., Gatford, K. L., Liravi, B., Kim, D., ... Bischof, R. (2016). Development of an experimental model of maternal allergic asthma during pregnancy. The Journal of Physiology, 594(5), 1311 - 1325. https://doi.org/10.1113/JP270752
Clifton, Vicki L. ; Moss, Timothy J. M. ; Wooldridge, Amy L. ; Gatford, Kathryn L. ; Liravi, Bahar ; Kim, Dasom ; Muhlhausler, Beverly S. ; Morrison, Janna L. ; Davies, Andrew ; De Matteo, Robert ; Wallace, Megan J. ; Bischof, Robert. / Development of an experimental model of maternal allergic asthma during pregnancy. In: The Journal of Physiology. 2016 ; Vol. 594, No. 5. pp. 1311 - 1325.
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title = "Development of an experimental model of maternal allergic asthma during pregnancy",
abstract = "We studied the effects of preconceptional allergen sensitisation and repeated airway allergen challenges during pregnancy on maternal immune and airway functions during pregnancy, and maternal, fetal and placental phenotype in late pregnancy in sheep. This protocol induced maternal responses consistent with an allergic asthmatic phenotype. During pregnancy, lung resistance and the eosinophil influx induced by allergen challenges increased progressively in allergic sheep, and in late pregnancy airway smooth muscle content was greater in allergic than control ewes. Effects on fetal growth and development were consistent with those of maternal asthma in humans. Maternal allergic asthma decreased relative fetal weight by 12 , reduced fetal lung expression of surfactant protein B, and altered placental morphology. This provides an animal model in which to identify mechanisms underlying fetal effects of maternal asthma in pregnancy, including fetal physiological responses to exacerbations, and to evaluate responses to clinically used treatments and novel interventions. ABSTRACT: Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 +/- 1 days gestational age (term, approximately 147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12 ) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48 lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.",
author = "Clifton, {Vicki L.} and Moss, {Timothy J. M.} and Wooldridge, {Amy L.} and Gatford, {Kathryn L.} and Bahar Liravi and Dasom Kim and Muhlhausler, {Beverly S.} and Morrison, {Janna L.} and Andrew Davies and {De Matteo}, Robert and Wallace, {Megan J.} and Robert Bischof",
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Clifton, VL, Moss, TJM, Wooldridge, AL, Gatford, KL, Liravi, B, Kim, D, Muhlhausler, BS, Morrison, JL, Davies, A, De Matteo, R, Wallace, MJ & Bischof, R 2016, 'Development of an experimental model of maternal allergic asthma during pregnancy' The Journal of Physiology, vol. 594, no. 5, pp. 1311 - 1325. https://doi.org/10.1113/JP270752

Development of an experimental model of maternal allergic asthma during pregnancy. / Clifton, Vicki L.; Moss, Timothy J. M.; Wooldridge, Amy L.; Gatford, Kathryn L.; Liravi, Bahar; Kim, Dasom; Muhlhausler, Beverly S.; Morrison, Janna L.; Davies, Andrew; De Matteo, Robert; Wallace, Megan J.; Bischof, Robert.

In: The Journal of Physiology, Vol. 594, No. 5, 03.2016, p. 1311 - 1325.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Development of an experimental model of maternal allergic asthma during pregnancy

AU - Clifton, Vicki L.

AU - Moss, Timothy J. M.

AU - Wooldridge, Amy L.

AU - Gatford, Kathryn L.

AU - Liravi, Bahar

AU - Kim, Dasom

AU - Muhlhausler, Beverly S.

AU - Morrison, Janna L.

AU - Davies, Andrew

AU - De Matteo, Robert

AU - Wallace, Megan J.

AU - Bischof, Robert

PY - 2016/3

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N2 - We studied the effects of preconceptional allergen sensitisation and repeated airway allergen challenges during pregnancy on maternal immune and airway functions during pregnancy, and maternal, fetal and placental phenotype in late pregnancy in sheep. This protocol induced maternal responses consistent with an allergic asthmatic phenotype. During pregnancy, lung resistance and the eosinophil influx induced by allergen challenges increased progressively in allergic sheep, and in late pregnancy airway smooth muscle content was greater in allergic than control ewes. Effects on fetal growth and development were consistent with those of maternal asthma in humans. Maternal allergic asthma decreased relative fetal weight by 12 , reduced fetal lung expression of surfactant protein B, and altered placental morphology. This provides an animal model in which to identify mechanisms underlying fetal effects of maternal asthma in pregnancy, including fetal physiological responses to exacerbations, and to evaluate responses to clinically used treatments and novel interventions. ABSTRACT: Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 +/- 1 days gestational age (term, approximately 147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12 ) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48 lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.

AB - We studied the effects of preconceptional allergen sensitisation and repeated airway allergen challenges during pregnancy on maternal immune and airway functions during pregnancy, and maternal, fetal and placental phenotype in late pregnancy in sheep. This protocol induced maternal responses consistent with an allergic asthmatic phenotype. During pregnancy, lung resistance and the eosinophil influx induced by allergen challenges increased progressively in allergic sheep, and in late pregnancy airway smooth muscle content was greater in allergic than control ewes. Effects on fetal growth and development were consistent with those of maternal asthma in humans. Maternal allergic asthma decreased relative fetal weight by 12 , reduced fetal lung expression of surfactant protein B, and altered placental morphology. This provides an animal model in which to identify mechanisms underlying fetal effects of maternal asthma in pregnancy, including fetal physiological responses to exacerbations, and to evaluate responses to clinically used treatments and novel interventions. ABSTRACT: Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 +/- 1 days gestational age (term, approximately 147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12 ) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48 lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.

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