Timothy Regnault

Maternal, Fetal & Newborn Health Dr. Timothy Regnault
Scientist
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Affiliations

Scientist, Division of Maternal, Fetal & Newborn Health, Children’s Health Research Institute
Associate Professor, Departments of Obstetrics & Gynaecology and Physiology & Pharmacology, Schulich School of Medicine, Western University

How my research helps children

Our research aims to understand how babies that do not grow normally, because of too little nutrition or too much nutrition while still inside the womb, change their metabolism, the way the body uses energy, to live and grow. These babies change their metabolism, or are reprogrammed, under the unfavorable in utero environment to survive inside the womb. However these programming changes are now postulated to lead to an increased risk of childhood and adult non-communicable diseases such as insulin resistance, obesity, hypertension and the origins of heart disease, collectively termed the metabolic syndrome. Our work aims to understand and develop ways to modulate the changes in these children's metabolism inside and outside the womb. Further, our work helps those children that are born after these abnormal in utero situations to grow correctly as adults, limiting the risk of the metabolic diseases later in life.

Research

Current Research Activities

My research activities are focused around the in utero origins of adult metabolic disease. Through the use of cell based and animal/human model systems, and technologies such as PET/CT and MRI, we investigate, how stressors such as hypoxia, oxidative stress and infection and poor maternal diet during fetal life, impact placental, and fetal blood vessel, liver, adipose, kidney, heart and muscle development and function. These studies aim to address what reprogramming events these stressors initiate in the womb and what are the implications of these outcomes for the onset and severity of childhood and adult diseases, such as insulin resistance and associated non-communicable diseases including obesity, cardiovascular disease and hypertension. More importantly the research sets out to understand the degree of plasticity of these changes by investigating, if they are locked after being reprogrammed, or are there windows of opportunity for us to intervene and rescue some of these unfavorable in utero-induced changes.

Future Research Plans

We will continue to address the above studies, while at the same time embarking on some new exciting investigations aimed at the understanding the effect of poor maternal diet intake during pregnancy and of obesity upon future offspring health and possible intervention options in these and low birth weight outcomes.

Research Team

Jeni Thompson (Ph.D. candidate) and David Kao (M.Sc.candidate) are the two graduate trainees in the laboratory. Jeni works on the in utero development of vascular dysfunction as it relates to hypertension in later life, while David’s work deals with investigating how insults in utero impact upon muscle nutrient transport and metabolism and its ultimate effect upon insulin sensitivity.  The diseases of vascular dysfunction and insulin resistance are the two most important precursors for the development of metabolic syndrome in later life.

Together with Dr. de Vrijer (Maternal Fetal Medicine consultant) we also study modulators of preterm rupture of membranes during pregnancy, with a special interest in the effects obesity plays in this and its regulation of fetomembrane nutrient transport and utilization. With Dr. Andreana Bütter (Pediatric cardiologist), we are also undertaking studies investigating the molecular origins and possible interventions of dysfunction lungs following congenital diaphragmatic hernia in utero.

With Drs. Lee (Robarts imaging) and Staples (Biology) we continue our insulin sensitivity work in IUGR offspring, specifically addressing in utero induced alterations in muscle insulin sensitivity with PET and associated body composition changes with CT and mitochondrial function studies.

Dr. Lin Zhao is our senior research technician and together we supervise a number of Residents, Medical and undergraduate student research projects. Recently these projects have included investigations of low protein inductions of hypertension in growth retarded fetuses, effects of infection upon human fetal blood and amnion and the effect of placental insufficiency upon fetal hepatic antioxidative capacity.

Future Research Plans

We will continue to address the above studies, while at the same time embarking on some new exciting investigations. Recently Katie Belgrave has joined our group as a M.Sc. candidate and will be focusing her efforts upon adverse in utero environment modulation of fetal and adult muscle mitochondrial activity and how these changes are modulated in situations of high fat/carbohydrate diets. Additionally, we will expand our pilot studies investigating the role that hypoxia during development may have upon cardiac remodeling, diastolic dysfunction, and increased sensitivity to ischemic injury in adult life.

Awards & Grants

Awards & Grants

Funding in support of Fetal endotoxin exposure and regulation of amino acid supply – Awarded by Natural Sciences and Engineering Research Council (NSERC)

Funding in support of Telomerase Therapy for Intrauterine Growth Restriction (IUGR) – Awarded by Lawson Health Research Institute (LHRI)

Funding in support of In utero insults and adult insulin resistance – Awarded by Canadian Institute of Health Research (CIHR)

Funding in support of Fetal endotoxin exposure and regulation of amino acid supply – Awarded by Natural Sciences and Engineering Research Council (NSERC)

Funding in support of High Resolution Multisensor Respirometer – Awarded by Natural Sciences and Engineering Research Council (NSERC)

Funding in support of Altered programming of muscle oxidative capacity in cell and animal hypoxic models – Awarded by Western University

Funding in support of The impact of dietary fatty acids on inflammation during pregnancy, lactation and fetal development – Awarded by Natural Sciences and Engineering Research Council (NSERC)

Funding in support of A laboratory for investigating the role of fetal programming in Metabolic Syndrome – Awarded by Canada Foundation for Innovation (CFI)

Funding in support of Measuring Changes in Nuclear Receptor Binding During Fetal and Neonatal Development Using Chromatin Immunoprecipitation (ChIP) – Awarded by Natural Sciences and Engineering Research Council (NSERC)

Funding in support of The hypoxic induced cellular release of the amino acid osmolyte, taurine: Regulation and interaction with cellular hypoxia induced apoptosis in a fetal guinea pig model of growth restriction – Awarded by Western University

Funding in support of Increased skeletal muscle cationic amino acid transporter, CAT2A, mRNA concentrations occurs under hypoxia, the result of posttranscriptional cleavage of nuclear retained CAT mRNA – Awarded by Lawson Health Research Institute (LHRI)

Funding in support of The molecular mechanisms of hypoxic induced impaired amino acid transport in FGR – Awarded by Lawson Health Research Institute (LHRI)

Funding in support of An examination of how hypoxia inflencues cellular energy balance and impacts oxidative properties – Awarded by Western University

Funding in support of The effects of hypoxia upon fetal tissue methylation status – Awarded by Western University

Recent Publications

Publications

Male gender promotes an increased inflammatory response to lipopolysaccharide (LPS) in umbilical vein blood
Kim-Fine S, Folliott SA, Lee JS, Greenspoon JA, Summers K, Regnault TRH, deVrijer B
J Maternal-Fetal & Neonatal Medicine. 2012 April

The Long and Short of it: The Role of Telomeres in Fetal Origins of Adult Disease
Hallows SE, Regnault TRH, Betts DH
J Pregnancy - Special issue; Experimental and clinical advances in the mechanisms underlying abnormal pregnancy outcomes. 2012 October

Central Stiffening in Adulthood Linked to Aberrant Aortic Remodeling Under Suboptimal Intrauterine Conditions
Thompson JA, Gros R, Richardson B, Regnault TRH
American Journal of Physiology - Heart and Circulatory Physiology. 2011 Sept; IF:4.69

Chronic Intrauterine Hypoxia Interferes with Aortic Development in the late Gestation Ovine Fetus
Thompson JA, Richardson BS, Gagnon R, Regnault TRH
Journal of Physiology. 2011 May 3. [Epub ahead of print]

In utero origins of adult insulin resistance and vascular dysfunction
Thompson JA, Regnault TRH
Seminars in Reproductive Medicine. 2011; 29(3):211-224

Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle
Thorn SR, Regnault TR, Brown LD, Rozance PJ, Keng J, Roper M, Wilkening RB, Hay WW Jr, Friedman JE
Endocrinology. 2009 Jul;150(7):3021-30

Effects of early gestation GH administration on placental and fetal development in sheep
Wright CD, Orbus RJ, Regnault TR, Anthony RV
J Endocrinol. 2008 Jul;198(1):91-9

Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep
Rozance PJ, Limesand SW, Barry JS, Brown LD, Thorn SR, LoTurco D, Regnault TR, Friedman JE, Hay WW Jr
Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E365-70

Ontogeny of endothelial nitric oxide synthase mRNA in an ovine model of fetal and placental growth restriction
Ziebell BT, Galan HL, Anthony RV, Regnault TR, Parker TA, Arroyo JA
Am J Obstet Gynecol. 2007 Oct;197(4):420.e1-5

The expression of ovine placental lactogen, StAR and progesterone-associated steroidogenic enzymes in placentae of overnourished growing adolescent ewes
Lea RG, Wooding P, Stewart I, Hannah LT, Morton S, Wallace K, Aitken RP, Milne JS, Regnault TR, Anthony RV, Wallace JM
Reproduction. 2008 Jun;135(6): 889

Heterodimeric amino acid transporters in the placenta--a workshop report
Regnault TR, Kudo Y, Glazier J, Roos S, Lewis RM, Jansson T
Placenta. 2007 Apr;28 Suppl A:S103-6

Altered placental and fetal expression of IGFs and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy
de Vrijer B, Davidsen ML, Wilkening RB, Anthony RV, Regnault TR
Pediatr Res. 2006 Nov;60(5):507-12

Development and mechanisms of fetal hypoxia in severe fetal growth restriction
Regnault TR, de Vrijer B, Galan HL, Wilkening RB, Battaglia FC, Meschia G
Placenta. 2007 Jul;28(7):714-23

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction
Barry JS, Davidsen ML, Limesand SW, Galan HL, Friedman JE, Regnault TR, Hay WW Jr
Exp Biol Med (Maywood). 2006 May;231(5):566-75

In vivo techniques for studying fetoplacental nutrient uptake, metabolism, and transport
Regnault TR, Hay WW Jr.
Methods Mol Med. 2006;122:207-24

Additional publications

Contact

Contact

Phone: (519) 661-2111, x83528
Fax: (519) 661-3827
Email: tim [dot] regnault [at] uwo [dot] ca
Website: http://www.uwo.ca/physpharm/faculty/regnault_timothy.html

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