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Dr Amanda N. Sferruzzi-Perri

My interest lies in understanding the aetiology of pregnancy complications and the regulation of developmental processes in a wider context. My laboratory has been investigating the environmental and genetic control of placental morphogenesis and function and its relevance for fetal development, maternal health and the long-term programming of disease.
Dr Amanda N. Sferruzzi-Perri

University Lecturer in Physiology

Royal Society Dorothy Hodgkin Research Fellow (2014-2019)

Lister Institute for Preventative Medicine Research Fellow

Amanda Sferruzzi-Perri is accepting applications for PhD students.


Office Phone: +44 (0) 1223 333807, Lab: +44 (0) 1223 746744

Research Interests

In developed countries, more than 15% of women develop pregnancy complications which are associated with placental insufficiency and fetal and maternal morbidity and mortality. Such complications include fetal growth restriction, premature birth, gestational diabetes and preeclampsia. To better understand the aetiology of these pregnancy complications and developmental processes in a wider context, my laboratory has been investigating the environmental and genetic control of placental morphogenesis and function and its relevance for fetal development, maternal health and the long-term programming of disease. Our work combines novel genetic tools and established environmental models, with in vivo functional assays and cellular, histological and molecular techniques in vitro. Our work also employs manipulations of the insulin-like growth factor- phosphoinositide-3 kinase (IGF-PI3K) system to identify its importance in metabolism and developmental physiology and as a tool to more widely address the following research aims of the lab:

1) To better understand the molecular mechanisms governing placental trophoblast differentiation and function.

2) To examine how the placenta may influence the metabolic and cardiovascular systems of the mother and thus, her capacity to partition resources to the developing fetus.

3) To determine how the placenta senses and responds to the maternal environment and thereby regulates fetal growth and development.

4) To identify whether changes in maternal-fetal resource allocation due to altered placental function has consequences for the developmental and health program of the offspring later in life.

Collaborators

Prof Abby Fowden
Prof Graham Burton
Dr Andrew Murray
Prof Dino Giussani
Dr Miguel Constancia, Dept of Obstetrics and Gynaecology, University of Cambridge
Dr Mike Deery, Cambridge Centre for Proteomics, University of Cambridge
Prof Sue Ozanne, Institute of Metabolic Sciences, Cambridge
Dr David Williams, University College London
Prof Martha Lappas and Dr Padma Murthi, University of Melbourne
Prof Anna David, University College London
Prof Joris Vriens, KY Leuven
Dr Linus Shao, University of Gothenburg

Current funding

Royal Society
Academy of Medical Sciences
MRC
EU commission
Lister Institute of Preventative Medicine
Isaac Newton Trust
A*Star

 

Teaching

Co-organiser of the Part II Course

Examiner and demonstrator for Part 1B Human Reproduction

Lecturer for the Placental Biology Course, Centre for Trophoblast Research

Key Publications

Colson A, Sonveaux P, Debiève F, Sferruzzi-Perri AN. Adaptations of the human placenta to hypoxia: opportunities for interventions in fetal growth restriction. In press Human Reproduction Update (ID: HRU-20-0050).

Lopez-Tello J and Sferruzzi-Perri AN (2021) Fused placentas: Till birth do us part. Placenta 103: 177-9.

Napso T, Zhao X, Ibañez Lligoña M, Sandovici I, Kay RG, Gribble FM, Reimann F, Meek CL, Hamilton RS, Sferruzzi-Perri AN. Unbiased placental secretome characterization identifies candidates for pregnancy complications. Available on Bioarchive https://biorxiv.org/cgi/content/short/2020.07.12.198366v1 

Zhang Y, Hu M, Jia W, Liu G, Zhang J, Wang B, Li J, Cui P, Li X, Lager S, Sferruzzi-Perri AN, Han Y, Liu S, Wu X, Brännström M, Linus Shao L, Billig H (2020) Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats. Journal of Endocrino​logy 246:247-263.

 Christoforou ER and Sferruzzi-Perri AN (2020) Invited review: Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress. Cellular and Molecular Life Sciences 77:4861-4898.

Fowden AL, Camm EJ, Sferruzzi-Perri (2020) Invited review: Placental consequences of maternal obesity. Current Vascular Pharmacology In press BMS-CVP-2019-HT11-953-1.

Aykroyd BRL, Tunster ST, Sferruzzi-Perri AN (2020) Igf2 deletion alters mouse placenta endocrine capacity in a sexually-dimorphic manner. Journal of Endocrinology 246:93-108.

De Clercq K*, Lopez-Tello J, Vriens J, Sferruzzi-Perri AN (2020) Double-label immunohistochemistry to assess labyrinth structure of the mouse placenta with stereology. Placenta 94:44-47. * Contributed equally. 

Kaitu’u-Lino TJ, MacDonald TM, Cannon P, Nguyen TV, Hiscock RJ, Haan N, Hastie R, Dane KM, Middleton AL, Bittar I, Sferruzzi-Perri AN, Pritchard N, Harper A, Hannan AJ, Kyritsis V, Crinis N, HuiL, Walker SP, Tong S (2020) Circulating SPINT1 is a marker of placental insufficiency and fetal growth restriction. Nature Comms 11(1):2411. 

Napso T, Hung Y-P, Davidge S, Care A, Sferruzzi-Perri AN (2019) Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rats. Scientific Reports 9:16916. 

Sferruzzi-Perri AN, López-Tello J, Napso T, Yong HE. Invited review: Exploring the causes and consequences of maternal metabolic maladaptations during pregnancy. Placenta 98:43-51. 

López-Tello J, Arias-Álvarez M, González-Bulnes A, Sferruzzi-Perri AN (2019) Rabbit models for studying intrauterine growth restriction and fetal programming. Molecular Reproduction & Development 86(12):1781-1809.

Musial B, Fernandez-Twinn, Duque-Guimaraes D, Carr SK, Fowden AL, Ozanne SE*, Sferruzzi-Perri AN* (2019) Exercise alters the molecular pathways of insulin signalling and lipid handling in maternal tissues of obese pregnant mice. Physiological Reports 7(16):e14202.

Lopez-Tello J, Perez-Garcia V, Khaira J, Kusinski L, Andreani, A, Grant I, Fernandez De Liger E, Cooper W, Hemberger M, Sandovici I, Constancia M, Sferruzzi-Perri AN (2019)  Interplay between fetal and trophoblast phosphoinositol 3-kinase (PI3K) p110α signalling modifies resource allocation to the growing fetus. eLIFE 8: e45282.

Lee CQR, Bailey A, Lopez-Tello J, Sferruzzi-Perri AN, Okkenhaug K, Moffett A, Hemberger M, Rossant J (2019) Inhibition of phosphatidylinositol-3-kinase signaling promotes the stem cell state of trophoblast. Stem Cells 37:1307-1318

Zhang Y, Zhao W, Xu H, Hu M, Guo X, Jia W, Liu G, Li J, Cui P, Lager SM, Sferruzzi-Perri AN, Li W, Wu X, Brännström M, Shao LR, Billig H (2019) Mechanisms of PCOS-induced fetal loss: evidence for placental mitochondrial abnormalities and elevated ROS production in PCOS-like pregnant rats.  J Physiology 597:3927-3950.

Sandovici I, Georgopoulou A, Hufnagel AS, Schiefer SN, Santos F, Hoelle K, Lam BYH, Yeo GSH, Burling K, López-Tello J, Reiterer M, Fowden AL, Burton GJ, Sferruzzi-Perri AN, Branco CM, Constância M (2019) Fetus-derived IGF2 matches placental development to fetal demand. Available on Bioarchives: https://www.biorxiv.org/content/early/2019/01/16/520536

De Clercq K, Persoons E, Napso T, Luyten C, Parac-Vogt TN, Sferruzzi-Perri AN, Kerckhofs G and Vriens J  (2019) Simultaneous 3D morphological analysis of the mature murine placenta and its vasculature using contrast enhanced microCT. PNAS 116(28):13927-13936.  

Hu M, Zhang Y, Guo X, Jia W, Liu G, Zhang J, Li J, Cui P, Sferruzzi-Perri AN, Han Y, Wu X, Ma H, Brännström M, Shao LR and Billig H (2019) Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant ROS production. American Journal of Physiology Endocrino​logy and Metabolism 316:E794-E809. 

Sferruzzi-Perri AN, Higgins J, Vaughan OR, Murray AJ, Fowden AL (2019) Placental mitochondria adapt developmentally and in response to hypoxia to support fetal growth. PNAS 116(5):1621-1626.

Lopez-Tello J, Jimenez-Martinez MA. Herrera E, Krause B*, Sferruzzi-Perri AN* (2018) Progressive uterine artery occlusion in the guinea pig leads to defects in placental structure that relate to fetal growth. Placenta 72-73:36-40. *joint last author.

Napso T*, Yong HEJ*, Lopez-Tello J, Sferruzzi-Perri AN (2018). The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation. Frontiers in Physiology. 9:1091. *Joint first author.

Camm EJ, Botting KJ, Sferruzzi-Perri AN Near to one’s heart: the intimate relationship between the placenta and fetal heart. Invited Review. Frontiers in Physiology, 9:629.

Nuzzo AM*, Camm EJ*, Sferruzzi-Perri AN, Ashmore TJ, Yung HW, Spiroski AM, Sutherland MR, Logan A, Austin-Williams S, Burton GJ, Rolfo A, Todros T, Murphy MP,Giussani DA (2018) Placental adaptation to early-onset hypoxic pregnancy and mitochondria-targeted antioxidant therapy in the rat. American Journal of Pathology. 188:2704-2716. *joint first author.

Balmas E, Rana B, Hamilton RS, Shreeve N, Kieckbusch J, Aye I, Hawkes DA, Trotter S, López-Tello J, Yong H, Valenti S, Sferruzzi-Perri AN, Gaccioli F, McKenzie ANJ, Colucci F (2018) Maternal group 2 innate lymphoid cells control fetal growth and protect from endotoxin-induced abortion in mice. Available online on Bioarchive server: http://biorxiv.org/cgi/content/short/348755v1

Sferruzzi-Perri AN (2018) Balancing needs; Exploring the role of IGF2 signalling in materno-fetal resource allocation. Invited Review. Placenta, 64 Suppl 1:S16-S22.

Sferruzzi-Perri AN Assessment of placental transport function in studies of disease programming (2018). Invited Review. Methods in Molecular Biology, 1735:239-250.

Kwok A, Zvetkova I, Virtue S, Huang-Doran I, TomlinsonP, Bulger A, Hart D, Knox R, Franks S, Voschol P,  Vidal-Puig A, Sferruzzi-Perri AN, Jensen J, O’Rahilly S, Semple R (2017)C-terminal truncation of Pik3r1 in mice models human lipodystrophic insulin resistance uncoupled from dyslipidemia. Available online on Bioarchive server: https://www.biorxiv.org/content/early/2017/11/24/224485.

Decato BE, Lopez-Tello J, Sferruzzi-Perri AN, Smith AD, Dean MD (2017) DNA methylation divergence and tissue specialization in the developing mouse placenta, Molecular Biology and Evolution, 34(7):1702-1712.

Musial B, Vaughan OR, Ozanne SE, Fowden AL, Sferruzzi-Perri AN (2017) A diet high in sugar and fat causes glucose intolerance and fat deposition in the mother with consequences for feto-placental growth in mice, J Physiol,  595(14):4875-4892.

Sferruzzi-Perri AN, Sandovici I, Constancia M, Fowden AL (2017) Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth. Invited review, J Physiol, 595(15):5057-5093

Fernandez-Twinn D, Gascoin G, Musial B, Carr S, Duque-Guimaraes D, Blackmore H, Zahra M Alfaradhi, Loche E, Ferland-McCollough D, Bushell M, Sferruzzi-Perri AN, Fowden AL, Ozanne SE (2017) Exercise rescues obese mothers' insulin sensitivity, placental function and her offsprings' insulin sensitivity, Scientific Reports, 7:44650.

Nadkarni S,Smith J, Machado I,Sferruzzi-Perri AN, Kishore M Hass R, Mauro C, Williams D, Farsky S, Marelli-Berg F, Perretti M (2017) Neutrophils induce pro-angiogenic T cells with a regulatory phenotype in pregnancy, PNAS, 113(52):E8415-E8424.

Sferruzzi-Perri AN, Lopez-Tello J, Fowden AL, Constancia M (2016) Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation, PNAS113(40):11255-11260.

Sferruzzi-Perri AN, Camm EJ (2016) The programming power of the placenta, Frontiers in Physiology, 7:33.

Boulenouar B*, Doisne J-M*, Sferruzzi-Perri AN, Gaynor L, Kieckbusch J, Balmas E, Yung HW, Javadzadeh S, Volmer L, Hawkes DA, Phillips K, Brady H, Fowden AL, Burton GJ, Moffett A, Colucci F (2015) NFIL3-dependent natural killer cells mediate maternal adaptations to pregnancy, placental development and fetal growth, Frontiers in Immunology, 7:43* joint first author.

Musial B, Fernandez-Twinn, Vaughan OR, Ozanne SE, Voshol P, Sferruzzi-Perri AN, Fowden AL (2015) Proximity to delivery alters insulin sensitivity and glucose metabolism in pregnant mice, Diabetes, Jan 6. pii: db151531.

Higgins JS, Vaughan OR, Fernandez De Liger E, Fowden AL, Sferruzzi-Perri AN (2015) Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy, J Physiol, 594(5):1341-56.

Ito M, Sferruzzi-Perri AN, Edwards CA, Adalsteinsson BT, Allen SE, Loo TH, Kitazawa M, Kaneko-Ishino T, Ishino F, Stewart CL, Ferguson-Smith AC (2015) A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development, Development, 142(14):2425-30.

Standen P, Sferruzzi-Perri AN, Taylor R, Heinemann G, Zhang JV, Highet AR, Pringle KG, Owens JA, Kumarasamy V, Lumbers ER, Roberts CT (2015) Maternal insulin-like growth factor 1 and 2 differentially affect the renin-angiotensin system during pregnancy in the guinea pig, Growth Horm IGF Res, 25(3):141-7.

Skeffington KL, Higgins JS, Mahmoud AD, Evans AM, Sferruzzi-Perri AN, Fowden AL, Yung HW, Burton GJ, Giussani DA, Moore LG (2015) Hypoxia, AMPK activation and uterine artery vasoreactivity,J Physiol, 594(5):1105-11.

Vaughan OR, Fisher HM, Dionelis KN, Jefferies EC, Higgins JS, Musial B, Sferruzzi-Perri AN, Fowden AL (2015) Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice, J Physiol, 593(5):1307-21.

Fowden AL, Forhead AJ, Sferruzzi-Perri AN, Burton GJ, Vaughan OR (2014) Endocrine regulation of placental phenotype, Placenta, Suppl 1:S50-9.

Sferruzzi-Perri AN, Vaughan OR, Haro M, Cooper WN, Musial B, Charalambous M, Pestana D, Ayyar S, Ferguson-Smith AC, Burton GJ, Constancia M, Fowden AL (2013) An Obesogenic Diet Modifies nutrient partitioning and fetal Growth Trajectory, FASEB J, 27(10):3928-37.

Sferruzzi-Perri AN, Vaughan OR, Forhead AJ, Fowden AL (2013) Hormonal and nutritional drivers of intrauterine growth, Current Opinion in Clinical Nutrition & Metabolic Care, 16(3):298-309.

Sferruzzi-Perri AN, Owens JA, Pringle KG, Roberts CT (2011) The neglected role of maternal endocrine insulin-like growth factors in regulating fetal growth, Invited Review, Journal of Physiology, 589(Pt 1):7-20.

Sferruzzi-Perri AN, Vaughan OR, Coan PM, Suciu MC, Darbyshire R, Constancia M, Burton GJ, Fowden AL (2011) Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice, Endocrinology, 52(8):3202-12.

Plain English

During pregnancy, more than 15% of women develop complications like fetal growth restriction, premature birth, gestational diabetes and excessive blood pressure (preeclampsia). These complications threaten the life and health of the mother and baby during pregnancy and predispose to disease in later life. Our lab studies how genetic and environmental factors interact with one another to influence the placenta, an organ that develops and performs many vital functions during pregnancy. In doing so, we hope to find ways to prevent the pregnancy complications and improve the health and wellbeing of women and their babies.

summer 2018.4.JPG

Back row: Miss Minhui Lu (Masters student), Miss Marta Ibañez Lligoña (Masters student), Dr Samantha Lean (Postdoc), Miss Amanda Rodgers (PhD student), Miss Edina Gulacsi (Research technician), Dr Jorge Lopez-Tello (Postdoc)
Middle row: Mr Panayiotis Laouris (Undergraduate student), Dr Tina Napso (Postdoc), Miss Emma Siragher (PhD student),  Bethany Aykroyd (PhD student), Efthimia Christoforou (PhD student), Miss Whitney Ching (Masters student), Miss Sophie Wilson (undergraduate student), Dr Katrien De Clercq (Visiting postdoc), Dr Esteban Salazar Petres (Postdoc) 
Front: Dr Amanda Sferruzzi-Perri (Lab head)


 

 

 

teaching france

Above: Teaching researchers in France how to dissect the placenta.

 image1

Above: Histological samples of the murine placenta showing its gross architecture and below: the detailed structure of the materno-feto interface (FC=fetal capillary, MBS= maternal blood space, T=trophoblast).

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