Wlodek laboratory: Fetal, postnatal & adult physiology & disease laboratory

Research Overview

Professor Mary Wlodek
Professor Mary Wlodek

The environment in early life has a major impact on a healthy start to life as well as lifelong health and disease risk. Being born small for gestational age (~10% of all births) remains a major problem for obstetric and perinatal medicine because it increases morbidity and mortality around the time of birth. Many studies worldwide have shown that babies born small are at increased risk of developing adult cardiovascular, renal and metabolic disease, the major causes of death and disability in Australia. Our group is renowned for the successful experimental model that mimics human growth profiles, organ deficits and phenotypes observed in babies born small who are susceptible to adult diseases. My laboratory is internationally recognised as one of the few in the world performing complex whole animal physiological studies exploring of the adult, pregnancy and transgenerational consequences of being born small. Using strategic and interdisciplinary collaborations, across Institutions, Industry and Faculties, I maximise research opportunities from my complex and long term animal studies to explore gender-specific clinically relevant disease outcomes. Critical to translational outcomes is the incorporation of various innovative treatments and interventions including nutritional (cross-fostering, diet), exercise, pregnancy, transgenerational (heritable vs maternal environment by embryo transfer) and impact of stress and alcohol during pregnancy. Our studies have substantially advanced our understanding of the consequences of being born small and have led to a sustained and accelerating series of highly cited publications in highly ranked journals.

histology sections of heart cardiomyocytes
Figure 1: Heart cardiomyocytes


To address our research aims we employ a number of approaches including uteroplacental insufficiency surgery to induce fetal growth restriction, embryo transfer techniques to identify maternal vs fetal influences and cross-fostering to determine prenatal vs postnatal influences. In our models we explore the beneficial impact of endurance exercise training and characterise activity and open circuit indirect calorimetry (Columbus Lab Animal Management System). We use a range of in vivo techniques to measure rat physiological parameters including postnatal milk intake and composition, growth, food intake and body composition, telemetry and tail-cuff blood pressure, renal function, intraarterial & intraperitoneal glucose tolerance test, insulin challenge test and echocardiography. Our in vitro analytical approaches include real-time PCR, Western Blotting, unbiased sterology to determine nephron and cardiomyocyte number, DXA & pQCT bone analysis, histology, immunohistochemistry as well as hormone, metabolite, electrolyte, growth factor measurements.

histology of blastocyst
Figure 2: Blastocyst

Staff


Dr Jessica Griffith, Postdoctoral Fellow:  jessica.griffith@unimelb.edu.au
Kristina Anevska, PhD Student:  K.Anevska@latrobe.edu.au
Dayana Mahizir, PhD Student: n.mahizir@student.unimelb.edu.au
Yeukai Mangwiro, PhD Student: ytmangwiro@students.latrobe.edu.au
Lily Chen, Honours Student

Research Publications

Recent Reviews

  1. Gallo LA, Tran M, Master JS, Moritz KM, Wlodek ME. Maternal adaptations and inheritance in the transgenerational programming of adult disease. Cell Tissue Res 2012; 349: 863-880.
  2. Gallo LA, Tran M, Moritz KM, Wlodek ME. Developmental programming: Variation in early growth and adult disease. Clin Exp Physiol Pharm 2013; 40: 795-802.
  3. Gatford KL, Kaur G, Falcão-Tebas F, Wadley GD, Wlodek ME, Laker RC, Ebeling PR, McConell GK. Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction.  Am J Physiol 2014; 306: E999-E1012.
  4. Briffa JF, McAinch AJ, Romano T, Wlodek ME, Hryciw DH.  Leptin in pregnancy and development: a contributor to adulthood disease.  Am J Physiol 2015; 308: E335-E350.
  5. Richter VF, Briffa JF, Mortiz KM, Wlodek ME, Hryciw DH. Developmental programming of renal dysfunction. Clin Exp Pharmacol Physiol 2016; 43: 135-141.
  6. Mahizir D, Briffa JF, Hryciw DH, Wadley GD, Moritz KM, Wlodek ME. Maternal obesity in females born small: pregnancy complications and offspring disease risk. Mol Nutr Food Res 2016; 60: 8-17.
  7. Cheong JN, Wlodek ME, Moritz KM, Cuffe JSM. Programming of maternal and offspring disease: Impact of growth restriction, fetal sex and transmission across generations. J Physiol 2016; 594: 4727-4740.

Select Publications 2007 to 2010

  1. Wlodek ME, Mibus AL, Tan A, Siebel AL, Owens JA, Moritz K. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol 2007; 18: 1688-1696.

    Subject of “JASN This Month’s Highlights” J Am Soc Nephrol 2007; 18:1617-1618, and the “JASN Editorial” J Am Soc Nephrol 2007; 18: 1626-1629.

  2. Wlodek ME, Westcott KT, Siebel AL, Owens JA, Moritz KA. Growth restriction induced before or after birth reduces nephron number and increases blood pressure in male rats. Kidney International 2008; 74: 187-195.
  3. Siebel AL, Mibus AL, De Blasio MJ, Westcott KT, Morris MJ, Prior L, Owens J, Wlodek ME. Improved lactational nutrition and postnatal growth ameliorates impaired glucose tolerance by uteroplacental insufficiency in males. Endocrinology 2008; 149: 3067-3076.
  4. Moritz K, Mazzuca MQ, Siebel AL, Mibus A, Arena D, Tare M, Owens JA, Wlodek ME. Uteroplacental insufficiency causes a nephron deficit and renal insufficiency but no hypertension with ageing in females. J Physiol 2009; 587(11): 2635-3646.
  5. Mazzuca MQ, Wlodek ME, Dragomir N, Parkington H, Tare M. Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring. J Physiol 2010; 588: 1997-2010.
  6. Siebel AL, Gallo LA, Guan TC, Owens JA, Wlodek ME. Cross-fostering and improved lactation ameliorates deficits in endocrine pancreatic morphology in growth-restricted adult male rat offspring. J DoHaD 2010; 1: 234-244.

Select Publications 2011 to present

  1. *Laker RC, *Gallo LA, Wlodek ME, Siebel AL, Wadley GD, McConell GK. Short-term exercise training early in life restores deficits in pancreatic β-cell mass associated with growth restriction in adult male rats. Am J Physiol 2011; 301: E931-E940.
    *Laker & Gallo joint first authors.
  2. Laker RC, Wlodek ME, Wadley GD, Gallo LA, Meikle PJ,  McConell GK. Exercise early in life in rats that were born small does not normalize reductions in skeletal muscle PGC-1α in adulthoodAm J Physiol 2012; 302: E1221-E1230.
  3. *Gallo LA, *Tran M, Moritz KM, Mazzuca MQ, Parry LJ, Westcott K, Jefferies J, Cullen-McEwen L, Wlodek ME. Cardio-renal and metabolic adaptations during pregnancy in female rats born small: Implications for maternal health and second generation fetal growth. J Physiol 2012; 590: 617-629.
    *Gallo & Tran joint first authors

  4. Subject of “J Physiol Perspectives” 2012; 590(5): 1019.
  1. Black MJ, Siebel AL, Gezmish O, Moritz K, Wlodek ME. Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate. Am J Physiol 2012; 302: R1101-R1110.
  2. Mazzuca MQ, Tare M, Parkington HC, Dragomir NM, Parry LJ, Wlodek ME. Uteroplacental insufficiency programs vascular dysfunction in non-pregnant rats. J Physiol 2012; 590(14): 3375-3388.
  3. Tare M, Parkington HC, Bubb KJ, Wlodek ME. Uteroplacental insufficiency and lactational environment separately influence arterial stiffness and vascular function in adult male rats. Hypertension 2012; 60:378-386.
  4. Gallo LA, Tran M, Moritz KM, Jefferies AJ, Wlodek ME. Pregnancy in aged female rats born small: cardio-renal and metabolic adaptations and second generation fetal growth restriction. FASEB J 2012; 26: 4337-4347.
    Our article is featured on the October 2012 cover
  5. Tran M, Gallo LA, Jefferies AJ, Moritz KM, Wlodek ME. Transgenerational metabolic outcomes associated with uteroplacental insufficiency. J Endocrinology 2013; 217: 105-118.
  6. Tran M*, Gallo LA*, Hanvey A, Jefferies AJ, Westcott KT, Cullen-McEwen LA, Gardner DK, Moritz KM, Wlodek ME. Embryo-transfer cannot delineate between the maternal environment and embryo-specific effects in the transgenerational transmission of disease. Am J Physiol 2014; 306: R607-R618.  
    * Tran & Gallo joint first authors.
  7. Gallo LA, Tran M, Cullen-McEwen LA, Denton KM, Jefferies AJ, Moritz KM, Wlodek ME. Transgenerational programming of fetal nephron deficits and sex-specific adult hypertension in rats. Reprod Fertil Develop 2014; 26: 1032-1043.
  8. Master JS, Zimanyi MA, Yin KV, Moritz KM, Gallo LA, Tran M, Wlodek ME, Black MJ. Transgenerational left ventricular hypertrophy and hypertension in male rat offspring following uteroplacental insufficiency. Clin Exp Physiol Pharm 2014; 41: 884-890.
  9. Master JS, Thouas GA, Harvey AJ, Sheedy JR, Hannan NJ, Gardner DK, Wlodek ME. Low female birth weight and maternal age programs next generation blastocyst development. Reproduction 2015; 149: 497-510.
  10. Master JS. Thouas GA, Harvey AJ, Sheedy JR, Hannan NJ, Gardner DK, Wlodek ME. Fathers that are born small program alterations in the next generation preimplantation rat embryo. J Nutrition 2015; 145: 876-883.
  11. Wadley GD, Laker RC, McConell GK, Wlodek ME. Endurance training in early life results in long-term programming of heart mass in rats. Physiol Reports 2016; 4: 1-14; e12720.
  12. Cheong JN, Cuffe JSM, Jefferies AJ, Moritz KM, Wlodek ME. Adrenal, metabolic and cardio-renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy. J Physiol 2016; 594: 6055-6068.
  13. Cheong JN, Cuffe JSM, Jefferies AJ, Anevska K, Moritz KM, Wlodek ME. Sex-specific metabolic outcomes in offspring of female rats born small or exposed to stress during pregnancy. Endocrinology 2016; 157: 4104-4120.
  14. Briffa JF, O'Dowd R, Moritz KM, Romano T, Jedwab LR, McAinch AJ, Hryci, DH*, Wlodek ME.* Uteroplacental insufficiency reduces rat plasma leptin concentrations and alters placental leptin transporters: ameliorated with enhances milk intake and nutrition.  J Physiol Accepted 09/02/17. 
    * Wlodek & Hryciw joint senior authors.