sharon tay presentation.ppt · 2011-01-11 · Sharon Tay School of Animal Biology Sharon grew up in...
Transcript of sharon tay presentation.ppt · 2011-01-11 · Sharon Tay School of Animal Biology Sharon grew up in...
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Sharon TaySchool of Animal Biology
Sharon grew up in the city of Singapore where farms are almost non e istent She mo ed to Perth hen she as inalmost non-existent. She moved to Perth when she was in high school, and had her first taste of agriculture at a sheep
shearing demonstration. After completing a Molecular Biology degree at Murdoch University she did an honoursBiology degree at Murdoch University, she did an honours project which involved sequencing a gene associated with
skin and wool development, with the aim of identifying genetic markersgenetic markers.
Sharon was inducted into the world of agriculture when she was offered a PhD project investigating the effect of high-salt
diets during pregnancy in ewes and how this would affectdiets during pregnancy in ewes and how this would affect their offspring’s physiology. It is part of a national project
looking at innovative grazing systems that incorporate perennial plants that can provide the motivation and
Institute of
Agriculture
p p presources for improved agricultural landscapes.
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Institute of
i lAgriculture
Physiology of lambs is altered by the high-salt y gy y gintake of their mothers during pregnancy
Sharon Tay
Institute of
Agriculture
Supervisors: Assoc/Prof Dominique Blache & Dr Dean Revell
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A high-salt intake during pregnancy changed in the offspring:
• The ‘hardware’the number & size of functional units in the kidneykid ikidney size
• The ‘software’ that regulates salt balanceThe software that regulates salt balanceexpression of genes
hormonal control
Due to foetal programming
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Foetal Programming
• Maternal environment affects biology of offspringEg. nutrition
• Molecular mechanisms better understood
• My work - how high-salt intake programmes• My work - how high-salt intake programmes kidney function of the offspring
Why high-salt diets?Institute of
Agriculture
Why high-salt diets?
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ProblemDryland salinityDryland salinity
M j bl i A t li• Major problem in Australia
• Affects ~1.8M Ha of land in WAarea increasing
• Affected areas turned intoAffected areas turned into wasteland
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Innovative solution
• Use saltbush (Atriplex spp.) to revegetate & regeneraterevegetate & regenerate
landscapes
• Food resource for livestockbut a high salt load (25%).… but a high salt load (25%)
• Capacity to excrete salt limits salt (& feed) intake
Saltbush in Yealering, WA
• Capacity to excrete salt limits salt (& feed) intakeenergy intake vs expenditure
affects animal productionInstitute of
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affects animal production
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Ewes consuming high-salt diet during pregnancy:
Did ff d i b• Did not affect reproduction but
H d ff t ff i• Had an effect on offspring
altered response to oral salt dose. i.e. l ti f lt/ t b lregulation of salt/water balance (Digby et al., 2009)
Ch d t h d d ft ?Change due to hardware and software?
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Programming of the hardware
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Nephron
• Structural & functional unit of kidneynephron
• Regulates concentration of water & soluble substances e g sodium salts
p
soluble substances e.g. sodium salts
• Functions regulated by hormones• Functions regulated by hormones (software)
• Control of blood pressure
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Glomerulus
• In the Bowman’s capsule glomerulusBlood enters via
renal arteryIn the Bowman s capsule
• Nephron’s initial filtering component
• Water, salts reabsorbed into bloodto maintain blood volumeto maintain blood volume
• Filters waste from blood & excreted &as urine ureter
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HypothesesH thHypothesesHypotheses
Feeding ewes a high salt diet during pregnancy:
• leads to histological changes in nephrons (kidney) of offspring
Effects observed in the young offspring persist into later life
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Experimental approach
Ewe fed control diet Ewe fed ‘salty’ dietEwe fed ‘salty’ dietEwe fed control diet during pregnancy
Ewe fed salty diet during pregnancy
Ewe fed salty diet during pregnancy
5 month old offspring
3 year old offspring
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HypothesesGl l b & i i l b
HypothesesGlomerular number & size in lambs
Glomerular number (per 10 transects)
Glomerular radius (µM)(per 10 transects) radius (µM)
Control offspring 185a 61a
High-salt offspring 154b 73b
~20% change
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HypothesesKid i h
HypothesesKidney weights
Lambs(g)
Adults(g)(g) (g)
Control offspring 122 175a
High-salt offspring 119 154b
10% decrease
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Programming of the software
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Renin Angiotensin System
A i t iRenin
Angiotensin I
Angiotensinogen
Angiotensin I-Converting Enzyme (ACE)
Angiotensin I
Angiotensin II
Vasopressin (antidiuretic hormone)Aldosterone
Sodium reabsorption & stimulation of thirst reflex
Water retention & stimulation of thirst reflexstimulation of thirst reflex stimulation of thirst reflex
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Regulation of water intake & urinary salt excretion
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Renin Angiotensin System
A i t i* Renin
Angiotensin I
Angiotensinogen
salt
Angiotensin I-Converting Enzyme (ACE)
Angiotensin I
Angiotensin II
Vasopressin (antidiuretic hormone)* Aldosterone
Sodium reabsorption & stimulation of thirst reflex
Water retention & stimulation of thirst reflexstimulation of thirst reflex stimulation of thirst reflex
Institute of
Agriculture
Regulation of water intake & urinary salt excretion
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HypothesesHypothesesHypothesesHypotheses
Feeding ewes a high salt diet during pregnancy:
• alters post natal expression of renin gene• alters post-natal expression of renin gene
• decreases plasma renin and aldosterone in offspring
Effects observed in the young offspring persist intoEffects observed in the young offspring persist into later life
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Experimental approach
Ewe fed control diet Ewe fed ‘salty’ dietEwe fed ‘salty’ dietEwe fed control diet during pregnancy
Ewe fed salty diet during pregnancy
Ewe fed salty diet during pregnancy
5 month old offspring
3 year old offspring
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R i iRenin gene expression
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R i iRenin gene expression
Lambs Adults
Control offspring 1.4a 1.2a
High-salt offspring 1.0b 0.5b
30-40% decrease
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Pl iPlasma renin
Lambs(ng/mL/hr)
Adults(ng/mL/hr)( g ) ( g )
Control offspring 10.0a 5.7a
High-salt offspring 8.0b 4.8b
15-20% decrease
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Plasma aldosteronePlasma aldosterone
Lambs(pg/mL)
Adults(pg/mL)
Control offspring 45a 12.6a
High-salt offspring 51b 15.5b
10-20% increase
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HypothesesDNA MethylationHypotheses• One of the mechanisms of foetal programming
• Changes gene expression but not DNA sequence
T T C G AT T A C G A C C
CHCH33CHCH33
AA AA TTTC C GGGG
CHCHCHCH
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CHCH33CHCH33
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DNA methylation-kidneyDNA methylation kidney
Lambs(% methylation)
Adults(% methylation)
Control offspring 3.3a 2.5a
High-salt offspring 4.8b 3.7b
30-35% increase
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Experimental approachEwe fed control diet during pregnancy
Ewe fed ‘salty’ diet during pregnancy
Ewe fed ‘salty’ diet during pregnancyduring pregnancy during pregnancyduring pregnancy
5 month old offspring
3 year old offspring3 year old offspring
Dietary salt challenge
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Urinary sodium excretion adultsUrinary sodium excretion - adults
Control diet(g/day)
High-salt diet(g/day)(g y) (g y)
Control offspring 4 59
High-salt offspring 4 55
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Summary:
Foetal programming by high salt intake of:
y
• nephrogenesis in offspring
• regulation of renin-angiotensin system
• So, profound changes in soft and hardware for lifep g
But, no effect on offspring’s capacity to excrete saltBut, no effect on offspring s capacity to excrete salt
Are high salt offspring more metabolically efficient?Institute of
Agriculture
Are high salt offspring more metabolically efficient?
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Practical consequences
• saltbush offspring fared better when grazed saltbush as adultsas adults
increased weight gain
increased fleece weight(Chadwick et al 2009)(Chadwick et al., 2009)
• long term animal performance?
metabolic efficiency
f t l i t t l?Institute of
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foetal programming as a management tool?
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Acknowledgements
Dr Dean Revell & Assoc/Prof Dominique BlacheDr Dean Revell & Assoc/Prof Dominique Blache
UWA School of Animal BiologyUWA School of Animal Biology
CSIRO Li t k I d t iCSIRO Livestock Industries
Future Farm Industries CRC
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Practical consequences
• saltbush offspring fared better when grazed saltbush as adultsas adults
increased weight gain
increased fleece weight(Chadwick et al 2009)(Chadwick et al., 2009)
• long term animal performance?
metabolic efficiency
f t l i t t l?Institute of
Agriculture
foetal programming as a management tool?