metabolic programming of zebrafish, danio rerio

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Metabolic Programming of Zebrafish, Danio rerio Physiological performance as explained by Dynamic Energy Budget Theory and life-cycle consequences of uranium induced perturbations April 23, 2012 - Public Doctoral Defense – Vrije Universiteit Starrlight Augustine 1 Promoteren: Prof.Dr.Sebastiaan A.L.M. Kooijman, Prof.Dr. Christelle Adam-Guillermin Copromotor: Dr. Béatrice Gagnaire

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Metabolic Programming of Zebrafish, Danio rerio. Physiological performance as explained by Dynamic Energy Budget Theory and life-cycle consequences of uranium induced perturbations. Starrlight Augustine. Promoteren: Prof.Dr.Sebastiaan A.L.M. Kooijman, Prof.Dr. Christelle Adam-Guillermin - PowerPoint PPT Presentation

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Page 1: Metabolic Programming  of Zebrafish,  Danio rerio

Metabolic Programming of Zebrafish, Danio rerio

Physiological performance as explained by Dynamic Energy Budget Theory and life-cycle consequences of uranium induced perturbations

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Starrlight Augustine

1Promoteren: Prof.Dr.Sebastiaan A.L.M. Kooijman, Prof.Dr. Christelle Adam-GuillerminCopromotor: Dr. Béatrice Gagnaire

Page 2: Metabolic Programming  of Zebrafish,  Danio rerio

Extinction

Context : Environmental Risk Assessment

Aquatic ecosystems are the recipient of byproducts of our industries:

How much of each type of compound can be released into the environment without inducing deleterious side effects?

U

UU

U

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Page 3: Metabolic Programming  of Zebrafish,  Danio rerio

Extinction

Context : Environmental Risk Assessment

Aquatic ecosystems are the recipient of byproducts of our industries:

How much of each type of compound can be released into the environment without inducing deleterious side effects?

U

UU

U

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Page 4: Metabolic Programming  of Zebrafish,  Danio rerio

Context: IRSN research programme ENVIRHOM-ECO

Major cities

Mine tailing storage sites still in use in 1989

Uranium mines and mine tailings storage in France

Mine tailing storage closed in in 1989

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Mission statement: Evaluate long term effects of chronic exposure to radionuclides on the ecosystem.

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Page 5: Metabolic Programming  of Zebrafish,  Danio rerio

From molecules to ecosystems …

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SpaceSpace

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Page 6: Metabolic Programming  of Zebrafish,  Danio rerio

From molecules to ecosystems …

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SpaceSpace

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Page 7: Metabolic Programming  of Zebrafish,  Danio rerio

From molecules to ecosystems …

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SpaceSpace

Growth + reproduction

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Page 8: Metabolic Programming  of Zebrafish,  Danio rerio

OECD test organism: zebrafish

>90 jours2-3 cm

5 jours0.45 cm

Embryo

Juvenile

Adult

BIRTHPUBERTY

>90 days2-3 cm

5 days0.45 cm

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Page 9: Metabolic Programming  of Zebrafish,  Danio rerio

Dynamic Energy Budget (DEB) Theory

Internal concen-tration

Enough Too much

NEC

Effects

General unified theory in biology created over 30 years ago (Kooijman 1993, 2000, 2010) which specifies the acquisition and use of energy for all organisms. The theory respects mass and energy balancing.

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NEC = No effect Internal Concentration

0

0

Too little

Page 10: Metabolic Programming  of Zebrafish,  Danio rerio

Phase I: characterizing the physiological performance of non-exposed zebrafish (the blank)

Growth and Reproduction at different food levels

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Literature data

Zebrafish DEB model

Ageing

Temperature

Starvation8

Page 11: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 12: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 13: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 14: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Storage

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 15: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Storage

MaintenanceProcesses specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 16: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Storage

Maintenance

Growth

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 17: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Storage

Maintenance

Growth

Development

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 18: Metabolic Programming  of Zebrafish,  Danio rerio

Results: metabolic programming uncovered

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Feeding

Digestion

Storage

Maintenance

Growth

Development

Processes specified by the DEB model

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Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Reproduction

Page 19: Metabolic Programming  of Zebrafish,  Danio rerio

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Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Results: metabolic programming uncovered

Augustine et al 2011aAugustine et al 2011bMueller et al 2012

Page 20: Metabolic Programming  of Zebrafish,  Danio rerio

Phase II: characterizing uranium induced deviations from the physiological performance of the blank

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Literature data

Zebrafish DEB model

0 nM U 84 nM U 420 nM U

Growth and Reproduction at three levels of uranium

Uptake and elimination

How effects depend on internal concentration

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Page 21: Metabolic Programming  of Zebrafish,  Danio rerio

Results: effects of uranium

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Uranium induces toxic effects almost as soon as it is internalized

Effects on -growth (early life stages) -maintenance (adults)

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Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Page 22: Metabolic Programming  of Zebrafish,  Danio rerio

Results: effects of uranium

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Dry mass (µg)

Age, d

Data: Stéphanie Bourrachot 2009Lines: DEB model predictions

1054 nM

0 nM

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Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Page 23: Metabolic Programming  of Zebrafish,  Danio rerio

Results: effects of uranium

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Allocation to reproduction is a continuous process

Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Page 24: Metabolic Programming  of Zebrafish,  Danio rerio

Results: effects of uranium

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Allocation to reproduction is a continuous process

Spawning is discontinuous, but when the organism does not spawn the mass invested in reproduction remains inside the individual

Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Page 25: Metabolic Programming  of Zebrafish,  Danio rerio

Results: effects of uranium

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Allocation to reproduction is a continuous process

Spawning is discontinuous, but when the organism does not spawn the mass invested in reproduction remains inside the individual

When energy assimilated from food no longer covers maintenance then missing energy is taken from that invested in reproduction

Feeding

Digestion

Storage

Growth

Development

Processes specified by the DEB model

Reproduction

Ageing

Maintenance

Page 26: Metabolic Programming  of Zebrafish,  Danio rerio

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140 10 20 30 400

500

1000

Experiment time, days

Cumulated number of eggs

Augustine et al 2012

Spawning

Page 27: Metabolic Programming  of Zebrafish,  Danio rerio

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140 10 20 30 400

500

1000

Experiment time, days

866 eggs spawned in total is about 0.36 g (fresh weight)

Cumulated number of eggs

Augustine et al 2012

Page 28: Metabolic Programming  of Zebrafish,  Danio rerio

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0.4

0.6

0.8

1

1.2

0 10 20 30 400

500

1000

Experiment time, days

Wet mass, g

Final observed mass

DEB model prediction for the blank

Cumulated number of eggs

Augustine et al 2012

Page 29: Metabolic Programming  of Zebrafish,  Danio rerio

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0.4

0.6

0.8

1

1.2About half the final mass of the fish was spawned !!

0 10 20 30 400

500

1000

Experiment time, days

Wet mass, g

Cumulated number of eggs

Final observed mass

DEB model prediction for the blank

Augustine et al 2012

Page 30: Metabolic Programming  of Zebrafish,  Danio rerio

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0.4

0.6

0.8

1

1.2

0 10 20 30 400

500

1000

Experiment time, days

Cumulated number of eggs

Wet mass, g

Final observed mass

DEB model prediction for the blank

DEB model prediction for increasing maintenance costs

Augustine et al 2012

Page 31: Metabolic Programming  of Zebrafish,  Danio rerio

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How do these results link back to the initial problem ?

• Uranium turns out to be toxic and effects show up as soon as it is internalized.

• The zebrafish DEB model is a very sensitive tool for detecting effects

• The model is also useful for interpreting data and comparing studies

• Effects on populations and ecosystems follow from effects on individuals

Page 32: Metabolic Programming  of Zebrafish,  Danio rerio

From individual to ecosystems …

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SpaceSpace

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From individual to molecules …

Page 33: Metabolic Programming  of Zebrafish,  Danio rerio

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Thank you for your attention

Thanks are due to: Magalie Floriani (TEM)Virginie Cavalie (ICP-AES, TEM)Sylive Pierrisnard (ILC)Sandrine Pereira (immuno-histochemistry)Alban Carlat (data collection)« LRE » Laboratory and many more …

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