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2nd GRF One Health Summit 2013
17-20 November, 2013, Davos, Switzerland

Prenatal Exposure to Bisphenol-A and
Postnatal ov...
Prevention, Detection/Diagnosis and
Treatment
• Cardiovascular diseases
 Leading cause of death all over the
world
 Caus...
Bisphenol-A (BPA)
• Widely used in the synthesis of
plastics
• Prevalent in the environment
• Weak estrogen
• Widespread e...
BPA on cardiovascular function

•
•
•
•
•

Higher urinary concentrations of BPA is associated with heart
disease (Melzer e...
Endocrine manipulations and cardiovascular
function
• Prenatal androgen programming causes
hypertension in female offsprin...
Prenatal BPA and postnatal overfeeding: Effects on
cardiovascular function
• Does prenatal exposure to BPA affect
cardiova...
Hypothesis

Prenatal BPA exposure in combination with
postnatal
overfeeding
would
produce
alterations in cardiovascular fu...
Experimental Design
• Pregnant sheep were given daily subcutaneous injections of
cottonseed oil (control) or BPA (0.5 mg/k...
Methods
• Animals were sedated with low dose of Xylazine and Ketamine
and placed in right lateral recumbency.
• An ultraso...
Prenatal BPA and postnatal overfeeding on heart rate
Prenatal BPA and postnatal overfeeding on blood pressure
Prenatal BPA and postnatal overfeeding on interventricular septal
thickness
Prenatal BPA and postnatal overfeeding on left atrial diameter
Prenatal BPA and postnatal overfeeding on left ventricular area
Prenatal BPA and postnatal overfeeding on interventricular
septal thickness
Prenatal BPA and postnatal overfeeding on end systolic and
diastolic volumes
End Diastolic Volume (ml)
Summary
Overfeeding produced a reduction in heart rate and
increase in blood pressure.
Prenatal BPA treatment prevented ...
Conclusions
 Prenatal BPA exposure decreases overfeeding-induced
hypertension, contrary to our expectations.
 The impact...
Disease Detection and Prevention Strategies
• Detection
– Already available techniques
• Conventional cardiovascular monit...
Acknowledgements
University of Michigan
• Dr. Vasantha Padmanabhan
• Dr. Almudena Veiga

Students
•Natalie Baca
•Dr. Ninit...
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Prenatal Exposure to Bisphenol-A and Postnatal overfeeding on cardiovascular function in a sheep model

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GRF 2nd One Health Summit 2013: Presentation by Puliyur S Mohankumar, Michigan State University

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Prenatal Exposure to Bisphenol-A and Postnatal overfeeding on cardiovascular function in a sheep model

  1. 1. 2nd GRF One Health Summit 2013 17-20 November, 2013, Davos, Switzerland Prenatal Exposure to Bisphenol-A and Postnatal overfeeding on cardiovascular function in a sheep model P.S. MohanKumar, A. Veiga-Lopez, V. Padmanabhan, S. M. MohanKumar Wed 1.1: Disease Detection and Prevention Technologies College of Veterinary Medicine Michigan State University
  2. 2. Prevention, Detection/Diagnosis and Treatment • Cardiovascular diseases  Leading cause of death all over the world  Cause huge economic loss  Multivariate causes • Prevention and early detection will help treatment and reduce mortality
  3. 3. Bisphenol-A (BPA) • Widely used in the synthesis of plastics • Prevalent in the environment • Weak estrogen • Widespread exposure to BPA – biomonitoring studies in tissue, circulation and urine (Vandernberg et al., Environ Health Perspect. 2010 Aug;118(8):1055-1070)
  4. 4. BPA on cardiovascular function • • • • • Higher urinary concentrations of BPA is associated with heart disease (Melzer et al., 2010) Higher urinary concentrations of BPA is associated with coronary artery disease (Melzer et al., Circulation 125: 1482-1490, 2012) Higher urinary concentrations of BPA is associated with obesity in children and adolescents [Trasende et al., JAMA. 2012 Sep 19;308(11):1113-21] Urinary BPA levels are significantly associated with peripheral arterial disease [Shankar et al., Environ Health Perspect. 2012 September; 120(9): 1297–1300] Urinary BPA levels are associated with hypertension (Shankar and Teppala, J Environ Public Health. 2012)
  5. 5. Endocrine manipulations and cardiovascular function • Prenatal androgen programming causes hypertension in female offspring – sheep model – King et al., 2009 Am J Physiol 292: E1837E1841 • Exposure to low levels of estradiol-17beta (20 ng/day) for a prolonged period of time (90 days) causes hypertension in rats – reversal by antioxidants – (Subramanian et al., 2011 – Am J Physiol 300: R1560-R1568).
  6. 6. Prenatal BPA and postnatal overfeeding: Effects on cardiovascular function • Does prenatal exposure to BPA affect cardiovascular function? • Whether postnatal overfeeding amplifies the effects of prenatal BPA exposure on cardiovascular function?
  7. 7. Hypothesis Prenatal BPA exposure in combination with postnatal overfeeding would produce alterations in cardiovascular function resulting in hypertension.
  8. 8. Experimental Design • Pregnant sheep were given daily subcutaneous injections of cottonseed oil (control) or BPA (0.5 mg/kg/day in cotton seed oil) from day 30 to 90 of gestation. • A subset of female offspring of these dams were overfed to increase bodyweight to ~30% over that of controls (overfed groupOF group). The remaining were fed a normal diet (Normal fed-NF group). • The cardiovascular function of adult females was assessed using non-invasive echocardiography at 21 months of age. • Blood pressure was measured using the tail cuff method.
  9. 9. Methods • Animals were sedated with low dose of Xylazine and Ketamine and placed in right lateral recumbency. • An ultrasound transducer probe of appropriate frequency (4 or 5S) was placed on the 4 or 5th inter-costal space to examine the heart. • Multiple parameters related to heart functions were determined using echo. • Changes in these parameters were analyzed using two-way ANOVA followed by Fisher’s LSD test.
  10. 10. Prenatal BPA and postnatal overfeeding on heart rate
  11. 11. Prenatal BPA and postnatal overfeeding on blood pressure
  12. 12. Prenatal BPA and postnatal overfeeding on interventricular septal thickness
  13. 13. Prenatal BPA and postnatal overfeeding on left atrial diameter
  14. 14. Prenatal BPA and postnatal overfeeding on left ventricular area
  15. 15. Prenatal BPA and postnatal overfeeding on interventricular septal thickness
  16. 16. Prenatal BPA and postnatal overfeeding on end systolic and diastolic volumes End Diastolic Volume (ml)
  17. 17. Summary Overfeeding produced a reduction in heart rate and increase in blood pressure. Prenatal BPA treatment prevented overfeeding-induced increase in blood pressure. Prenatal BPA exposure increased left ventricular area during systole similar to postnatal overfeeding.
  18. 18. Conclusions  Prenatal BPA exposure decreases overfeeding-induced hypertension, contrary to our expectations.  The impact of prenatal BPA exposure-induced increase in left ventricular area during systole is unclear.  Further studies are needed to systematically examine the cardiovascular effects of prenatal BPA exposure.
  19. 19. Disease Detection and Prevention Strategies • Detection – Already available techniques • Conventional cardiovascular monitoring – BP monitoring, Echo – Detection of marker proteins – New opportunities • Develop new cost effective biomarker panels • miRNAs related to cardiovascular function • Prevention – Education – Reduce, Reuse, Recycle – Neutralize
  20. 20. Acknowledgements University of Michigan • Dr. Vasantha Padmanabhan • Dr. Almudena Veiga Students •Natalie Baca •Dr. Ninitha Asirvatham Jeyaraj Michigan State University • Dr. Gregory Fink • Dr. Bari Olivier • Dr. A. Pease • Dr. F. Garcia • Dr. Arpita Vyas Funding •NIH (R01ES016541) •USDA – Michigan AgBio Research

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