Associate Professor Claire Roberts

Research Interests

1. Placental invasion and the blood supply to the placenta

Our group’s major current focus in research is on the development of the placenta and the vessels which supply it. A number of pathologies of pregnancy, including up to 50% of miscarriages, preeclampsia, intrauterine growth restriction (IUGR), preterm labour, unexplained stillbirth and placental abruption are characterised by an impaired cytotrophoblast invasion and inadequate response of the uterine spiral arteries to undergo physiological transformation. Together these conditions affect more than one quarter of pregnant women in developed societies. We aim to understand the factors that impair placental invasion and function and apply this understanding to determining which couples are at risk of developing serious pregnancy complications.

We are investigating the cellular and molecular mechanisms underlying the formation of vascular connections between the mother and fetus. The uterine arterioles which supply the placenta are invaded by placental cytotrophoblast cells and are dramatically remodelled to produce dilated compliant vessels which allow the 12 fold increase in blood flow to the uterus which is essential for normal placental, and hence fetal, growth. However, the mechanisms by which physiological transformation of these vessels occurs are poorly understood. We are currently delineating the cellular and molecular interactions between maternal decidua and fetal trophoblast during the normal transformation of the arterioles which supply the placenta. Our work focuses on the role of insulin-like growth factor II (IGF-II) in placental invasion and how oxygen interacts with IGF-II in early pregnancy.

2. Diagnosing risk for pregnancy complications

We were funded by Government of South Australia to develop predictive tests for couples’ risks for complications of late pregnancy, specifically preeclampsia, IUGR and pre-term birth. This is the SA SCOPE (SCreening fOr Pregnancy Endpoints) project (Clinical Director Professor Gus Dekker and Scientific Director A/Professor Claire Roberts). We have assembled a biobank of samples from women pregnant for the first time, their partners and babies. We are undertaking a targeted gene approach and aim to identify genes that determine a couple’s risk prior to the development of symptoms. These genes have already been shown to be important in the control of placental development. We have a particular interest in how the father imparts risk for pregnancy complications in the mother and baby.

3. Epigenetic programming of placental and fetal development

IGF-II and its specific membrane receptor, IGF2R, are imprinted genes which means that only one copy of the gene is expressed, the other having been silenced by DNA methylation. IGF-II is expressed from the paternal allele, while IGF2R is expressed only from the maternal allele. We have recently shown that both genes are important in controlling placental invasion. A number of factors can alter the methylation status of imprinted genes including maternal nutrition, ex vivo embryo culture and cloning. We have examined the effect of cloning, ex vivo embryo culture and periconceptional undernutrition on placental development and methylation of imprinted genes in the sheep.

 

4. Administration of IGFs to the pregnant guinea pig promotes placental function and fetal growth

Previous research in our laboratory showed that maternal undernutrition, a model of growth restriction, not only reduced fetal and placental growth and impaired placental differentiation and function but also altered the IGF axis in the mother with reductions in circulating IGF-I and –II and increases in some of the IGF binding proteins. These factors were associated with structural alterations in the placenta that reduce substrate supply to the fetus.

Recently, we administered either IGF-I or IGF-II to guinea pigs for two weeks in early to mid pregnancy and found significant positive effects on placental differentiation and function and fetal growth in late gestation. These data suggest that IGFs, and IGF-II in particular, could be administered to pregnant women at risk of fetal growth restriction to ameliorate the condition.

 

5. Factors that control placental efficiency in pigs

In pigs there is significant embryo mortality in the days following implantation when the placenta is establishing itself. In addition, placental insufficiency results in uterine overcrowding, hence reduced litter size and low birth weight piglets (runts). These runts have high morbidity and mortality. The pork industry is keen to increase litter size, birth weight and survival to weaning. One strategy is to select for placental efficiency. We are determining factors that control placental efficiency in pigs.

Staff, students and current research projects

Name	Position	Project
Assoc/Prof Claire Roberts	Research Leader
Dr Amanda Sferruzzi-Perri	NHMRC CJ Martin Postdoctoral Fellow	Currently in Cambridge University, UK
Dr Denise Furness	Postdoctoral Fellow	Prediction of adverse pregnancy outcome (PAPO)
Karen Rivers	Research Midwife	Prediction of adverse pregnancy outcome (PAPO)
Gary Heinemann	Research Assistant	Molecular control of placental development
Jamie Zhang	Research Assistant	SA SCOPE
Steven Thompson	Research Assistant	SA SCOPE
Dylan McCullough	Research Assistant	Novel molecular regulators of trophoblast invasion
Anita Peura	Research Assistant	A novel media formulation for embryo culture
Rachael Nowak	Postgraduate student	Diagnosing risk for pregnancy complications
Ang Zhou	Postgraduate student	Diagnosing risk for preeclampsia & IUGR
Dr Prabha Andraweera	Postgraduate student	Angiogenic factors in normal and complicated pregnancies
Dr Dee McCormack	Postgraduate student	Predicting risk for recurrent miscarriage
Jessica Laurence	Honours student	Vitamin D, the placenta and pregnancy outcome

Publications

Publications 2004- and Patents

55. McCowan LME, Chan E, Kenny L, Roberts CT, Dekker GA, North RA Risk factors for infants small for gestational age by customized birthweight centiles Obstetrics and Gynaecology Submitted 30.9.09

54. Kenny LC, Broadhurst DI, Dunn W, Brown M, North RA, McCowan L, Roberts CT, Cooper GJS, Kell DB, Baker PN Early Pregnancy Prediction of Preeclampsia Using Metabolomic Biomarkers Nature Medicine Submitted 23.9.09

53. Novakovic B, Wong N, Sibson M, Ng H-K, Morley R, Manuelpillai U, Down T, Rakyan V, Beck S, Hiendleder S, Roberts CT, Craig JM, Saffery R DNA methylation-mediated down regulation of DNMT1, is co-incident with, but not essential for, global hypomethylation in extraembryonic tissues Journal of Biological Chemistry Manuscript #JBC/2009/064956 Accepted subject to revision 4.10.09.2009

52. Gatford KL, Smits RJ, Collins CL, Argent C, De Blasio MJ, Roberts CT, Nottle MB, Kind KL, Owens JA (2009) Maternal responses to daily maternal porcine somatotropin injections during early-mid or early-late pregnancy in sows and gilts. Journal of Animal Science Manuscript #E-2009-2265, accepted 5 August 2009

51. *McArdle AM, Maduwegedera D, Moritz K, Flower RL, Wintour EM, Denton KM, Roberts CT (2009) Chronic maternal hypertension affects placental gene expression and differentiation in rabbits Journal of Hypertension Manuscript #JH-S-S-09-00352 Accepted

50. McArdle AM, Roberts CT, Maduwegedera D, Flower RL, Denton KM (2009) Chronic maternal hypertension reduces late gestation placental blood flow in rabbits American Journal of Physiology: Regulatory Integrative Comparative Physiology Manuscript # R-00202-2009 Accepted subject to revision

49. Pringle KG, Kind KL, Thompson JG, Roberts CT (2009) Oxygen and beyond: complex regulation of the establishment of pregnancy Human Reproduction Update In Press INVITED REVIEW.

48. Gatford KL, de Blasio M, Roberts CT, Nottle MB, Kind KL, van Wettere WH, Smits RJ, Owens JA (2009) Responses to maternal growth hormone injections or ractopamine during early-mid pregnancy are similar in primiparous and multiparous pregnant pigs Journal of Endocrinology 203(1):143-154.

47. Kho EM, McCowan LME, Roberts CT, Chan E, Black MA, Taylor RS, North RA, Dekker GA (2009) Duration of Sexual Relationship and Its Effect on Preeclampsia and Small for Gestational Age: a Multicentre Prospective Study Journal of Reproductive Immunology 82(1):66-73.    

46. *McArdle AM, Denton KM, Maduwegedera D, Moritz K, Flower RL, Roberts CT Ontogeny of placental structural development and expression of renin angiotensin system and 11β-HSD2 genes in the rabbit Placenta 30:590-598.

45. Sferruzzi-Perri AN, MacPherson AM, Roberts CT, Robertson SA Csf2 Null Mutation Alters Placental Gene Expression and Trophoblast Glycogen Cell and Giant Cell Abundance in Mice. Biology of Reproduction 81:207-221.

44. Lash GE, Ansari T, Bischof P; Burton G, Chamley L, Crocker I, Dantzer V, Desoye G, Drewlo S, Fazleabas A, Jansson T, Keating S, Kliman H, Lang I, Mayhew T, Meiri H, Miller R, Nelson DM, Pfarrer C, Roberts CT, Sammar M, Sharma S, Shiverick K, Strunk D, Turner M, Huppertz B (2009) IFPA Meeting 2008 Workshops Report Placenta 30, Supplement A, Trophoblast Research, 23:S4–S14.

43. Roberts CT, Maclaughlin S, Fletcher C, Wyss O, Robertson SA, Kleeman D, Walker SK, McMillen IC (2008) The peri-conception and pre-implantation environment and subsequent placental development Workshop on Embryo and Fetal Nutrition Havemeyer Foundation Monograph Series 21:33-35. INVITED REVIEW Available online at: http://www.havemeyerfoundation.org/PDFfiles/Monograph21.pdf

42. *Roberts CT, Owens JA, Sferruzzi-Perri AN (2008) Distinct actions of insulin-like growth factors (IGF) on placental development and fetal growth: lessons from mice and guinea pigs Placenta 29 Supplement A Trophoblast Research 22:S42-S47. INVITED REVIEW

41. *Sferruzzi-Perri AN, Owens JA, Standen P, Roberts CT (2008) Maternal insulin-like growth factor-II promotes placental functional development and fetal growth via the type 2 IGF receptor in guinea pigs. Placenta 29(4):347-355.

40. *Sferruzzi-Perri AN, Standen P, Owens JA, Taylor RL, Heinemann GK, Robinson JS, Roberts CT (2007) Early pregnancy maternal endocrine IGF-I programs the placenta for increased functional capacity throughout gestation Endocrinology 148(9):4362-70.

39. *Pringle KG, Kind KL, Thompson JG, Roberts CT (2007) Complex interactions between HIFs, IGF-II and oxygen in early murine trophoblasts Placenta 28(11-12):1147-1157.

38. *Sferruzzi-Perri AN, Owens JA, Standen P, Taylor R, Heinemann G, Robinson JS, Roberts CT (2007) Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. American Journal of Physiology: Endocrinology and Metabolism 292: E668-E676.

37. Pringle KG and Roberts CT (2007) New light on early post-implantation pregnancy in the mouse: roles for Insulin-Like Growth Factor-II (IGF-II)? Placenta  28(4):286-297.

36. Fletcher C, Roberts CT, Hartwich K, Walker S, McMillen IC (2007) Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise. Reproduction 133(1): 243-255.

35. *Sferruzzi-Perri AN, Owens JA, Pringle, KG, Robinson JS, Roberts CT (2006) Maternal insulin-like growth factor-I and –II act via different pathways to promote fetal growth. Endocrinology 147(7):3344-3355.

34. Ferguson-Smith AC, Moore T, Detmar J, Lewis A, Hemberger M, Jammes H, Kelsey G, Roberts CT, Jones H, Constancia M (2006) Epigenetics and Imprinting of the Trophoblast: Workshop Report. Placenta 27 Suppl. A:S122-S126.

33. Feil D, Lane M, Roberts CT, Kelley R, Edwards LJ, Thompson JG and Kind KL (2006) Effect of culturing mouse embryos under different oxygen concentrations on subsequent fetal and placental development Journal of Physiology 572(1):87-96.

32. *Roberts CT, Sferruzzi-Perri AN, Kind KL, Robinson JS and Owens JA (2005) Placental perturbations and pregnancy outcome: a common thread. Workshop on Comparative Placentology Havemeyer Foundation Monograph Series17:54-56.

31. MacLaughlin SM, Walker SK, Roberts CT, Kleeman DO and McMillen IC (2005) Periconceptional undernutrition alters the relationship between maternal body weight and condition and the growth of the placenta and fetus in singleton and twin pregnancies in the sheep Journal of Physiology 565(Pt 1):111-24.

30. Mühlhäusler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG and McMillen IC (2005) Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. Journal of Physiology 565(Pt 1):185-95.

29. Sjöblom C, Roberts CT, Wikland M and Robertson SA (2005) GM-CSF alleviates adverse consequences of embryo culture in programming placental morphogenesis and fetal and postnatal growth in mice. Endocrinology 146(5):2142-53.

28. Grant PA, Kind KL, Roberts CT, Sohlstrom A, Owens PC and Owens JA (2005) Late pregnancy increases hepatic expression of insulin-like growth factor-I in well nourished guinea pigs. Growth Hormone and IGF Research 15(2):165-71.

27. Kind KL, Roberts CT, Sohlstrom AI, Katsman A, Clifton PM, Robinson JS and Owens JA (2005) Chronic maternal feed restriction restricts growth but increases adiposity of the fetal guinea pig. American Journal of Physiology Regulatory Integrative Comparative Physiology 288(1):R119-126.

26. Gude NM, Roberts CT, Kalionis B, King  RG (2004) Growth and function of the normal human placenta. Thrombosis Research 114(5-6):397-407.

27. Robertson SA, Roberts CT, van Beijering E, Pensa K, Sheng Y, Shi T, Krilis S (2004) Significance of functional b2-glycoprotein I in reproductive outcome and pathology of anti-phospholipid antibodies in mice. Molecular Human Reproduction 10(6):409-416.

25. Carter AM, Hills F, O’Gorman DB, Roberts CT, Sooranna SR, Watson CS and Westwood M (2004) The insulin-like growth factor system in mammalian pregnancy – A workshop report. Placenta 25 Suppl:S53-S56.

24. White CA, Johansson M, Roberts CT, Ramsay AJ and Robertson SA (2004) Effect of interleukin-10 null mutation on maternal immune parameters, pregnancy success and LPS-induced fetal loss in mice. Biology of Reproduction 70(1):123-131.

 

Patents

*Roberts CT and Owens PC (2002) Regulation of cytotrophoblast cell differentiation and cell migration. Patent Cooperation Treaty Application # PCT/AU02/01226 filed 30 August 2002, International Publication Date 28 February 2004, WO2003/018781, Claiming priority #PR7331 from 30 August 2001. Licensed by Medicult A/S, Denmark. Currently being examined in Australia, Canada and Europe. Granted in USA. Granted in New Zealand.

*Roberts CT (2005) Compositions and methods for improving implantation, development and pregnancy outcomes. PCT # 2005903997 Filed 27 July 2006 Claiming priority from 27 July 2005 International Publication Date 1 February 2007 #WO2007/012117 A1 Licensed by Medicult A/S, Denmark. Filed in Australia, USA, Europe and China (Chinese application #200680032241.8).

*Roberts CT and Thompson SD (2008) IGF2 polymorphisms associated with pregnancy complications
Provisional patent application #2008902646 filed 27.5.2008 (Priority Date)

*Roberts CT (2008) Insulin gene polymorphisms associated with pregnancy complications
Provisional patent application #2008902733 filed 30.5.2008 (Priority Date)

*Roberts CT and Nowak R (2008) UPA polymorphisms associated with pregnancy complications
Provisional patent application # 2008902753 filed 2.6.2008 (Priority Date)

*Roberts CT (2008) Polymorphisms in genes of the renin angiotensin system associated with pregnancy complications Provisional patent application #2008903044 Filed 16.6.2008 (Priority Date)

*Roberts CT, Thompson SD, Zhou A, Andraweera P (2009) Polymorphisms associated with pregnancy complications #PCT/AU2009/000668 filed 27.5.2009 Claiming priority from 27.5.2008 incorporating Provisional patent applications #2008902646, #2008902646, # 2008902753 and #2008903044.

*Roberts CT, Furness DL, Andraweera P, Nowak R (2009) Maternal, paternal and neonatal polymorphisms associated with pregnancy complications Provisional patent application #2009…. Filed 21.8.2009 (Priority Date)

*Roberts CT, Furness DL, Andraweera P, Nowak R, Thompson SD, Zhou A (2009) Polymorphisms associated with pregnancy complications Provisional patent application #2009…. Filed 1.10.2009 (Priority Date)

 

International Patents Granted:

*Roberts CT and Owens PC (2007) Regulation of cytotrophoblast cell differentiation and cell migration.
US Patent 7,244,707. Issued July 2007.

*Roberts CT and Owens PC (2008) Regulation of cytotrophoblast cell differentiation and cell migration.
New Zealand Patent 531362 Issued 12 June 2008.

Expertise for Media Contact

Categories	Medicine and medical research, Fertility & reproduction
Expertise	Pregnancy complications; placenta; pre-term birth; preeclampsia; intrauterine growth restriction; fetus
Notes	Head, Placental Development Laboratory
Mobile	0406 381 575

Entry last updated: Sunday, 22 Nov 2009