Dr Sarah Delforce

Dr Sarah Delforce

Research Associate

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Dr Sarah Delforce is a postdoctoral researcher in the Pregnancy and Women's Health Group in the Hunter Medical Research Institute and is part of the Priority Research Centre for Reproductive Sciences.

Her research focusses on the role of the renin-angiotensin system (RAS) in pregnancy and reproductive health. Under the supervision of A/Prof Kirsty Pringle and Emeritus Prof Eugenie Lumbers, Sarah investigates the sex-specific regulation of inflammation and membrane integrity in the onset of labour.

She was awarded her PhD (Human Physiology) in April 2019. To date she has published 5 papers as first author (3 in Placenta, 1 in Reproduction and 1 in Endocrine Connections) as well as 3 middle author papers. She has presented her work both nationally and internationally. In the past few years she has successfully been a David Healy New Investigator Award Finalist twice as well as received ASMR Pecha Kucha Award in 2018.


Qualifications

  • Doctor of Philosopy, University of Newcastle
  • Bachelor of Biomedical Sciences, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle

Keywords

  • Preeclampsia
  • placenta
  • preterm birth
  • renin-angiotensin system
  • uterus

Fields of Research

Code Description Percentage
060699 Physiology not elsewhere classified 35
110399 Clinical Sciences not elsewhere classified 35
111499 Paediatrics and Reproductive Medicine not elsewhere classified 30

Professional Experience

UON Appointment

Title Organisation / Department
Research Associate University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Awards

Award

Year Award
2019 SRB ANZPRA New Investigator Award
Australian Society of Reproductive Biology

Prize

Year Award
2018 2018 ASMR Best Pecha Kucha Talk
Australian Society for Medical Research (ASMR)
2016 2016 Gordon Research Conference on Angiotensins Poster Presentation Award
Gordon Research Conferences
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (8 outputs)

Year Citation Altmetrics Link
2019 Arthurs AL, Lumbers ER, Delforce SJ, Mathe A, Morris BJ, Pringle KG, 'The role of oxygen in regulating microRNAs in control of the placental renin-angiotensin system.', Mol Hum Reprod, 25 206-217 (2019)
DOI 10.1093/molehr/gaz004
Citations Web of Science - 1
Co-authors Andrea Johns10, Kirsty Pringle, E Lumbers
2019 Delforce SJ, Lumbers ER, Ellery SJ, Murthi P, Pringle K, 'Dysregulation of the placental renin-angiotensin system in human fetal growth restriction.', Reproduction (Cambridge, England), 158 237-245 (2019) [C1]
DOI 10.1530/rep-18-0633
Co-authors Kirsty Pringle, E Lumbers
2019 Delforce SJ, Lumbers ER, Morosin SK, Wang Y, Pringle KG, 'The Angiotensin II type 1 receptor mediates the effects of low oxygen on early placental angiogenesis', Placenta, 75 54-61 (2019)

© 2018 Introduction: Placental development occurs in a low oxygen environment, which stimulates angiogenesis by upregulating vascular endothelial growth factor A (VEGFA), plasmin... [more]

© 2018 Introduction: Placental development occurs in a low oxygen environment, which stimulates angiogenesis by upregulating vascular endothelial growth factor A (VEGFA), plasminogen activator inhibitor-1 (SERPINE1) and the angiopoietin-2/-1 ratio (ANGPT2/1). At this time, Angiotensin II type 1 receptor (AT 1 R) is highly expressed. We postulated that the early gestation placental oxygen milieu, by stimulating the angiotensin (Ang) II/AT 1 R pathway, increases expression of proliferative/angiogenic factors. Methods: HTR-8/SVneo cells were cultured in 1%, 5% or 20% O 2 with the AT 1 R antagonist (losartan) for 48 h. mRNA and protein levels of angiogenic factors were determined by qPCR and ELISA. Angiogenesis and cell viability were assessed by HUVEC tube formation and resazurin assay. Results: Culture in low oxygen (1%) increased angiogenic VEGFA, SERPINE1 and placental growth factor (PGF) mRNA and VEGFA and SERPINE1 protein levels, and reduced anti-angiogenic ANGPT1, endoglin (ENG) and soluble fms-like tyrosine kinase-e15a (sFlt-e15a) mRNA (all P = 0.0001). At 1% oxygen, losartan significantly reduced intracellular VEGFA and SERPINE1 levels and secreted VEGF levels (P = 0.008, 0.0001 and 0.0001). HUVEC tube formation was increased in cells grown in HTR-8/SVneo conditioned medium from 1 to 5% cultures (all P = 0.0001). HUVECs cultured in medium from losartan treated HTR-8/SVneo cells had a reduced number of meshes, branching points and total branching length (P = 0.004, 0.003 and 0.0002). At 1% oxygen, losartan partially inhibited the oxygen-induced increase in cell viability (P = 0.0001). Discussion: Thus, AT 1 R blockade antagonised the low oxygen induced increase in pro-angiogenic factor expression and cell viability. Our findings highlight a role for an oxygen-sensitive Ang II/AT 1 R pathway during placentation.

DOI 10.1016/j.placenta.2018.12.001
Citations Web of Science - 1
Co-authors Kirsty Pringle, E Lumbers
2017 Delforce SJ, Lumbers ER, Pringle KG, 'Regulation of the prorenin - angiotensin system by oxygen and miRNAs; parallels between placentation and tumour development?', Placenta, 56 27-33 (2017) [C1]

© 2017 Elsevier Ltd Tissue renin-angiotensin systems (RASs) are involved in tissue growth and development as they are important regulators of angiogenesis, cell proliferation and ... [more]

© 2017 Elsevier Ltd Tissue renin-angiotensin systems (RASs) are involved in tissue growth and development as they are important regulators of angiogenesis, cell proliferation and migration. The placental RAS is most highly expressed in early gestation, at a time when the oxygen tension within the conceptus is reduced, and plays a key role in placental growth and development. Similar to the placenta, tumour development relies on proliferation, angiogenesis and invasion in order to grow and metastasize. The RAS is known to be upregulated in a variety of solid tumours, including ovarian, endometrial, cervical, breast and prostate. This review explores the roles of oxygen and microRNAs in regulating the normal expression of the placental RAS, providing insight into regulation of its development as well as the development of disease states in which the RAS is overexpressed. We propose that the placental RAS is downregulated by microRNAs that are suppressed during the physiologically normal ¿hypoxic¿ phase of early placentation. Suppression of these miRNAs allows the placental RAS to stimulate placental growth and angiogenesis. We propose that similar mechanisms may be at play in solid tumours, which are characterised by hypoxia.

DOI 10.1016/j.placenta.2017.03.007
Citations Scopus - 1Web of Science - 1
Co-authors Kirsty Pringle, E Lumbers
2017 Delforce SJ, Lumbers ER, de Meaultsart CC, Wang Y, Proietto A, Otton G, et al., 'Expression of renin-angiotensin system (RAS) components in endometrial cancer', ENDOCRINE CONNECTIONS, 6 9-19 (2017) [C1]
DOI 10.1530/EC-16-0082
Citations Scopus - 7Web of Science - 6
Co-authors E Lumbers, Rodney Scott, Nikki Verrills, Kirsty Pringle
2016 Delforce SJ, Wang Y, Van-Aalst ME, Corbisier De Meaultsart C, Morris BJ, Broughton-Pipkin F, et al., 'Effect of oxygen on the expression of renin-angiotensin system components in a human trophoblast cell line', Placenta, 37 1-6 (2016) [C1]

© 2015 Elsevier Ltd. All rights reserved. During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via u... [more]

© 2015 Elsevier Ltd. All rights reserved. During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin-angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor (AGTR1) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen (P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development.

DOI 10.1016/j.placenta.2015.11.011
Citations Scopus - 7Web of Science - 7
Co-authors E Lumbers, Kirsty Pringle
2016 Pringle KG, Delforce SJ, Wang Y, Ashton KA, Proietto A, Otton G, et al., 'Renin-angiotensin system gene polymorphisms and endometrial cancer', ENDOCRINE CONNECTIONS, 5 128-135 (2016) [C1]
DOI 10.1530/EC-15-0112
Citations Scopus - 6Web of Science - 6
Co-authors Kirsty Pringle, E Lumbers, Rodney Scott
2015 Lumbers ER, Wang Y, Delforce SJ, Corbisier de Meaultsart C, Logan PC, Mitchell MD, Pringle KG, 'Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin', Reproductive Biology and Endocrinology, 13 (2015) [C1]

© 2015 Lumbers et al. Background: In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In t... [more]

© 2015 Lumbers et al. Background: In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In this study we aimed to determined if the RAS was present in endometrial stromal cells and if decidualisation upregulated the expression of prorenin, the prorenin receptor ((P)RR) and associated RAS pathways. Immortalised human endometrial stromal cells (HESCs) can be stimulated to decidualise by combined treatment with medroxyprogesterone acetate (MPA), 17ß-estradiol (E 2 ) and cAMP (MPA-mix) or with 5-aza-2'-deoxycytidine (AZA), a global demethylating agent. Methods: HESCs were incubated for 10days with one of the following treatments: vehicle, MPA-mix, a combination of medroxyprogesterone acetate (MPA) and estradiol-17ß alone, or AZA. Messenger RNA abundance and protein levels of prorenin (REN), the (P)RR (ATP6AP2), angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (PAI-1) were measured by real-time PCR and ELISA's, respectively. Promyelocytic zinc finger (PLZF) and phospho-inositol-3 kinase (PIK3R1) mRNA abundances were also measured. Results: HESCs expressed the prorenin receptor (ATP6AP2), REN, AGT, ACE and low levels of AGTR1. MPA-mix and AZA stimulated expression of REN. Prorenin protein secretion was increased in MPA-mix treated HESCs. E 2 + MPA had no effect on any RAS genes. MPA-mix treatment was associated with increased VEGF (VEGFA) and PAI-1 (SERPINE1) mRNA and VEGF protein. Conclusions: An endometrial prorenin receptor/renin angiotensin system is activated by decidualisation. Since (P)RR is abundant, the increase in prorenin secretion could have stimulated VEGF A and SERPINE1 expression via Ang II, as both ACE and AGTR1 are present, or by Ang II independent pathways. Activation of the RAS in human endometrium with decidualisation, through stimulation of VEGF expression and secretion, could be critical in establishing an adequate blood supply to the developing maternal placental vascular bed.

DOI 10.1186/s12958-015-0127-8
Citations Scopus - 8Web of Science - 8
Co-authors Kirsty Pringle, E Lumbers
Show 5 more journal articles

Conference (4 outputs)

Year Citation Altmetrics Link
2018 Delforce S, Arthurs A, Drury H, Quinn R, Lumbers E, Pringle K, 'OXYGEN-INDUCED REGULATION OF PLACENTAL MICRORNA AND RENIN-ANGIOTENSIN SYSTEM EXPRESSION IN FIRST TRIMESTER CHORIONIC VILLI', PLACENTA, Tokyo, JAPAN (2018)
Co-authors E Lumbers, Kirsty Pringle
2018 Morosin S, Delforce S, Lumbers E, Pringle K, 'SYNCYTIALISATION OF PRIMARY HUMAN TROPHOBLAST AND BEWO CHORIOCARCINOMA CELLS: DO THE PRORENIN RECEPTOR AND SOLUBLE PRORENIN RECEPTOR PLAY A ROLE?', PLACENTA, Tokyo, JAPAN (2018)
Co-authors Kirsty Pringle, E Lumbers
2018 Arthurs AL, Delforce SJ, Lumbers ER, Pringle KG, 'PLACENTAL MIRNAS THAT TARGET THE RENIN-ANGIOTENSIN SYSTEM, AND THEIR EFFECT ON TROPHOBLAST PROLIFERATION', PLACENTA, Tokyo, JAPAN (2018)
Co-authors E Lumbers, Kirsty Pringle
2014 Delforce SJ, Pringle KG, Wang Y, Verrills NM, Scott RJ, Lumbers ER, 'THE FUNCTIONAL ROLE OF THE ENDOMETRIAL RENIN ANGIOTENSIN SYSTEM IN ENDOMETRIAL CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Rodney Scott, E Lumbers, Kirsty Pringle, Nikki Verrills
Show 1 more conference
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Grants and Funding

Summary

Number of grants 3
Total funding $7,500

Click on a grant title below to expand the full details for that specific grant.


20191 grants / $1,500

SRB ECR Collaborative Research Travel Grant$1,500

Funding body: Australian Society of Reproductive Biology

Funding body Australian Society of Reproductive Biology
Project Team

Sarah Delforce, Fiona Brownfoot

Scheme SRB ECR Collaborative Research Travel Grant Scheme
Role Lead
Funding Start 2019
Funding Finish 2019
GNo
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON N

20162 grants / $6,000

CSIRO ON Prime $5,000

Funding body: CSIRO - Commonwealth Scientific and Industrial Research Organisation

Funding body CSIRO - Commonwealth Scientific and Industrial Research Organisation
Project Team

Kirsty Pringle, Sarah Delforce, Riazuddin Mohamed

Scheme ON Prime
Role Investigator
Funding Start 2016
Funding Finish 2016
GNo
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON N

HMRI SA Future' Medical Research Travel Grant$1,000

Funding body: Hunter Medical Research Institute (HMRI)

Funding body Hunter Medical Research Institute (HMRI)
Project Team

Sarah Delforce

Scheme Unknown
Role Lead
Funding Start 2016
Funding Finish 2016
GNo
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON N
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Dr Sarah Delforce

Position

Research Associate
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email sarah.delforce@newcastle.edu.au
Phone (02) 4042 0343

Office

Room Level 3 East - 030
Building Hunter Medical Research Institute
Location New Lambton Heights

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