Associate Professor Vicki L Clifton B.Sc. (Newcastle) Ph.D (Newcastle)
Contact Details
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NHMRC Senior Research Fellow Faculty Health Sciences |
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Memberships
Society of Gynecologic Investigation
Australian Perinatal Society
International Federation of Placental Associations.
Endocrine Society of Australia.
Australian Society for Medical Research
Research Interests
I presently have two major areas of interest which are examining "The effect of asthma during pregnancy on placental function and fetal outcome" and “Determining the effects of fetal gender on maternal health”.
The effect of asthma during pregnancy on placental function and fetal outcome.
Asthma affects 12% of the Australian population and is expected to increase to 20% over the next 10 years. This rise will result in an increase in the number of women who suffer from asthma during pregnancy and could emerge as a major public health problem since asthma during pregnancy is associated with low birthweight babies. Lower birthweight itself is an increased risk factor for a number of adult diseases such as diabetes and coronary artery disease and thus the offspring of asthmatic women are at risk for numerous pathologies throughout life. Nevertheless, the specific mechanisms that cause low birthweight in asthmatic pregnancies are unknown. We currently have a lead in this important area. Our data so far indicates that asthma produces alterations in placental blood flow and glucocorticoid metabolism that are particularly pronounced when the fetus is female. Inhaled glucocorticoid therapy is protective of the effects of asthma on the fetus suggesting the involvement of inflammatory pathways. The long term objectives of our work are to elucidate the effects of asthma on fetal health and to design better ways to manage asthma during pregnancy to improve the outcome for the baby. The short term objective of this grant is to define whether inflammatory factors associated with asthma during pregnancy change placental function to adversely affect fetal development and whether these effects are related to the sex of the fetus.
Determining the effects of fetal gender on maternal health
We have observed that women using inhaled steroids
and pregnant with a female fetus, increased their inhaled steroid intake as
gestation progressed while women pregnant with a male fetus had no change in
their steroid intake. Similar findings have previously been reported. These
data suggest that as pregnancy progresses, pro-inflammatory pathways are upregulated
in the presence of a female fetus increasing the requirement for inhaled steroid
treatment. We assume a similar increase in inflammatory pathways occurs in those
mildly asthmatic women who do not use inhaled steroids and are pregnant with
a female. This data suggests that the presence of a female fetus alters maternal
inflammatory pathways.
Based on these findings our working model is that
a factor derived from the female fetus causes inflammatory factors associated
with maternal asthma to be up-regulated. These asthma associated-inflammatory
factors cause alterations in placental function that result in decreased fetal
growth.
The specific hypothesis to be tested for this study
is that sex specific factors derived from the female fetus alter bronchial smooth
muscle synthetic function. The long term objective of this study is to find
out why asthmatic women pregnant with a female fetus have a worsening of their
asthma during pregnancy and smaller sized babies. The short term objective of
this work is to examine how sex-specific factors from the fetus alter maternal
lung function.
Publications
Husband A.J. and Clifton V.L. (1989) Role of intestinal immunization in urinary tract defense. Immunology and Cell Biology 67: 371-376.
Clifton V.L., Husband A.J. and Kay D.J. (1992) Local immunity in the male reproductive tract. Immunology and Cell Biology 70: 301-307.
Kay, D.J., Clifton, V.L., Taylor J.S. and Boettcher, B. (1993) Anti-sperm antibodies and semen profiles in reanastomosed men. Reprod. Fertil. Dev 5: 135-139
Clifton, V.L., Read, M.A., Leitch, I.M., Boura, A.L.A., Robinson, P.J. and Smith, R. (1994) Corticotropin-releasing hormone causes vasodilatation in the human fetal-placental circulation. J Clin. Endocrinol. Metab. 79: 666-669.
Clifton, V.L., Read, M.A., Leitch, I.M., Boura, A.L.A., Robinson, P.J. and Smith, R. (1995) Corticotropin-releasing hormone-induced vasodilatation in the human fetal-placental circulation: involvement of nitric oxide-cyclic guanosine 3’5’-monophosphate-mediated pathway. J Clin. Endocrinol. Metab. 80: 2888-93
Clifton, V.L., Owens, P.C., Robinson, P.J. and Smith, R. (1995) Corticotropin-releasing hormone receptors in the human placenta. European J Endocrinol. 133:591-597
Clifton, V.L., Read, M.A., Boura, A.L.A., Robinson, P.J. and Smith, R. (1996) Adrenocorticotropin hormone causes vasodilatation in the human fetal-placental circulation. J Clin. Endocrinol. Metab. 81:1406-1410.
Clifton, V.L., Telfer, J.T., Teoh, T.C., Lye, S.J., Cameron, I.T. and Challis, J.R.G. (1998) Localisation of corticotropin-releasing hormone and pro-opiomelanocortin peptides in the human myometrium. J Clin Endocrinol Metab 83: 3716-3721.
Patel, F., Clifton, V.L., Chwalisz, K., and Challis, J.R.G. (1999) Steroidal regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua related to labor. J Clin Endocrinol. Metab 84: 291-299.
McLean, M., Bowman, M., Clifton, V., Smith, R. and Grossman, A. (2000) Expression of the heme oxygenase-carbon monoxide signalling system in human placenta. J Clin Endocrinol. Metab 85: 2345–9.
Clifton, V.L., Qing, G., Murphy, V.E.,, Schwartz, J., Madsen, G. and Smith, R. (2000) Characterisation and localisation of urocortin during human pregnancy. Placenta 21: 782-788.
Clifton, V.L., Giles, W.B., Smith, R., Bisits, A.T., Hempenstall, P., Kessell C.G. and Gibson, P.G. (2001) Alterations of placental vascular function in asthmatic pregnancies. American Journal of Respiratory and Critical Care Medicine 164:546-553.
Clifton, V.L., Crompton, R., Smith, R. and Wright I.M (2002) Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to gender. Journal of Clinical Endocrinology and Metabolism 87:267-270.
Clifton, V.L., Wallace, E. and Smith R. (2002) Short term effects of glucocorticoids in the human fetal-placental circulation in vitro. Journal of Clinical Endocrinology and Metabolism 87(6):2838-42.
Murphy, V.E., Zakar, T, Smith, R., Giles, W.B., Gibson, P.G. and Clifton, V.L. (2002) Reduced 11b hydroxysteroid dehydrogenase type 2 activity is associated with decreased birthweight centile in pregnancies complicated by asthma. Journal of Clinical Endocrinology and Metabolism 87: 1660-1668.
O’Dwyer, D.T., Clifton, V., Hall, A., Smith, R., Robinson, P.J. and Crock, P.A. (2002) Pituitary autoantibodies in lymphocytic hypophysitis target both g- and a-enolase- a link with pregnancy. Archives of Physiology and Biochemistry 110 (1-2): 94-8.
Holloway, A.C., Howe, D.C., Chan, G., Clifton, V.L., Smith, R. and Challis, J.R.G. (2002) Urocortin: A mechanism for the sustained activation of the HPA axis in late gestation ovine fetus? American Journal of Physiology- Endocrinology and Metabolism 283(1):E165-7.
Murphy, V.M. and Clifton, V.L. (2003) Alterations in human placental 11beta-hydroxysteroid dehydrogenase type 1 and 2 with gestational age and labour. Placenta 24: 739-744.
Crompton, R, Clifton, V.L., Bisits, A.T, Read, M.A., Smith, R. and Wright, I.M.R. (2003) Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways. J. Clin. Endocrinol. Metab. 88(11):5427-5432.
Murphy, V.E., Gibson, P.G., Giles, W.B., Zakar, T., Smith, R., Kessell, C.G., Bisits, A.T. and Clifton, V.L. (2003) Maternal asthma is associated with reduced female fetal growth. Am. J. Resp. Crit. Care. Med. 168(11):1317-1323.
Clifton, V.L. and Murphy, V.E. (2004) Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta: Trophoblast Research 25: S45-52.
Vanderlelie, J.L, Venardos, K., Clifton, V.L., Gude, N.M., Clarke, F.M. and Perkins, A.V. (2004) Increased biological oxidation and reduced anti-oxidant enzyme activity in pre-eclamptic placentae. Placenta (in press, accepted 8 Apr 04).
Johnson, R.F., Mitchell, C.M., Clifton, V.L. and Zakar, T. (2004) Regulation of 15-hydroxyprostaglandin dehydrogenase (PGDH) gene activity, messenger RNA processing and protein abundance in the human chorion at late gestation and labor. J. Clin. Endocrinol. Metab. (in press, accepted July 2004)
Clifton, VL., Vanderlelie, J. and Perkins, AV. (2004) Increased anti-oxidant enzyme activity and biological oxidation in placentae of pregnancies complicated by maternal asthma. Placenta (in press, accepted 27 OCT 04).
Murphy VE, Johnson RF, Wang YC, Akinsanya K, Gibson PG, Smith R and Clifton VL. (2005) The effect of maternal asthma on placental and cord blood protein profiles. Journal of the Society for Gynecologic Investigation. In press (Accepted 22.1.05).
Murphy VE, Gibson PG, Smith R and Clifton VL (2005) Asthma during pregnancy: mechanisms and treatment implications. European Respiratory Journal. In press (Accepted 30.12.04).
Murphy VE, Gibson PG, Talbot PI, Kessell CG, Clifton VL, Asthma self-management skills and the use of asthma education in pregnant women. Eur Resp J. Accepted 2.6.05.
Clifton VL, Crompton R, Read MA, Gibson PG, Smith R, Wright IMR. Microvascular effects of CRH in human skin vary in relation to estrogen concentration during the menstrual cycle. J Endocrinol. Accepted April 2005.
Clifton, VL Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth Cell and Tissue Research Accepted 9 Mar 2005
VE Murphy, P Gibson, P I Talbot and V L Clifton (2005) Severe asthma exacerbations during pregnancy and their association with adverse perinatal outcomes. Obstetrics and Gynecology Accepted August 2005
V Murphy, R F Johnson, Y Wang, K Akinsanya, PG Gibson, R Smith and V L Clifton (2005) Alterations in maternal plasma protein profiles in pregnant women with asthma. Respirology Accepted August 2005.
A Osei-Kumah, A J. Ammit, R Smith, Q Ge, V L. Clifton. (2005) Inflammatory Mediator Release in Normal Bronchial Smooth Muscle Cells is Altered by Pregnant Maternal and Fetal Plasma Independent of Asthma. Placenta accepted August 2005
Review Papers
Clifton, V.L. and Challis J.R.G. (1997) Placental corticotropin releasing hormone function. The Endocrinologist 7: 448-458.
Schwartz, J., Revskoy, S., Redei, E., Clifton, V., Smith, R. and Cherny, R. (2002) Corticotrophs and peptides. Archives of Physiology and Biochemistry 110 (1-2): 146-153.
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