Post on 12-Apr-2017
Pascale Chavatte-Palmer, Docteur vétérinaire, PhD, Directrice de Recherches à l’Institut National de la Recherche Agronomique
Jeudi 18 février
Liens entre nutrition périnatale et développement post-natal : les leçons des modèles animaux.
Diet before and during pregnancy and offspring health: lessons from animal models
PASCALE CHAVATTE-PALMER
UMRBDR,INRA,ENVA,UniversitéParisSaclay,78350,JouyenJosas,France
pascale.chavatte@jouy.inra.fr
Pascale CHAVATTE-PALMER4
Oddsratio:1,47 Oddsratio:1,36
Meta-analysisincluding>130.000patientsBirthweightasaproxyforfetalnutrition
Birthweight<2500g Birthweight>4000g
Harderetal,Am.J.Epidemiol.2007
CorrelationbetweenbirthweightandrisktodevelopType2diabetes
Pascale CHAVATTE-PALMER 5
Lumeyetal,1992,PaedPerinatalEpidemiol;Lumeyetal,1997,AmJPublicHealth;Painteretal,2005,Toxicology;Painteretal,2005,HumanReproduction;Heijmansetal,2008
Calories(kcal)
July1944
Jan1945
April1945
July1945
Oct1945
Oct1944
2500
0
500
1000
1500
2000
Famine
Control
TheDutchFamine(1944-1945)cohortstudy
Pascale CHAVATTE-PALMER 5
Lumeyetal,1992,PaedPerinatalEpidemiol;Lumeyetal,1997,AmJPublicHealth;Painteretal,2005,Toxicology;Painteretal,2005,HumanReproduction;Heijmansetal,2008
ADULTS
1sttrimester➔CVD,obesity2ndtrimester➔Hypertension3rdtrimester➔Glucosemetabolism
Calories(kcal)
July1944
Jan1945
April1945
July1945
Oct1945
Oct1944
2500
0
500
1000
1500
2000
Famine
Control
TheDutchFamine(1944-1945)cohortstudy
Pascale CHAVATTE-PALMER 5
Lumeyetal,1992,PaedPerinatalEpidemiol;Lumeyetal,1997,AmJPublicHealth;Painteretal,2005,Toxicology;Painteretal,2005,HumanReproduction;Heijmansetal,2008
Noeffectonfertility
BUTreducedbirthweightingrandchildrenIncreasedperinatalmortality
(3rdtrimester)?
ADULTS
1sttrimester➔CVD,obesity2ndtrimester➔Hypertension3rdtrimester➔Glucosemetabolism
Calories(kcal)
July1944
Jan1945
April1945
July1945
Oct1945
Oct1944
2500
0
500
1000
1500
2000
Famine
Control
TheDutchFamine(1944-1945)cohortstudy
Pascale CHAVATTE-PALMER 5
Lumeyetal,1992,PaedPerinatalEpidemiol;Lumeyetal,1997,AmJPublicHealth;Painteretal,2005,Toxicology;Painteretal,2005,HumanReproduction;Heijmansetal,2008
Noeffectonfertility
BUTreducedbirthweightingrandchildrenIncreasedperinatalmortality
(3rdtrimester)?
ADULTS
1sttrimester➔CVD,obesity2ndtrimester➔Hypertension3rdtrimester➔Glucosemetabolism
Calories(kcal)
July1944
Jan1945
April1945
July1945
Oct1945
Oct1944
2500
0
500
1000
1500
2000
Famine
Control
TheDutchFamine(1944-1945)cohortstudy
IGF2hypomethylationat60yearsofage
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/20156
TheDutchFamine(1944-1945)cohortstudy
Veenendaaletal.BJOG2013
Impacton2ndgenerationn=360,meanage37years
Throughthemaleline..
Sons'children Daughters'children
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/20157
Conception BirthFetaldevelopment Growth Adult
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/20157
Conception BirthFetaldevelopment Growth Adult
Nutritionormetabolicstatusoftheparents
Obesity,undernutrtion,diabetes…
Fetalgrowthadaptation
Epigenome,transcriptome,cells,tissues,organs
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/20158
Conception BirthFetaldevelopment Growth Adult
NeonatalPhenotype
Nutritionormetabolicstatusoftheparents
Obesity,undernutrition,diabetes…
Fetalgrowthadaptation
Epigenome,transcriptome,cells,tissues,organs
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/20159
Conception BirthFetaldevelopment Growth Adult
NeonatalPhenotype
Nutritionormetabolicstatusoftheparents
Obesity,undernutrition,diabetes…
Fetalgrowthadaptation
Epigenome,transcriptome,cells,tissues,organs
IncreasedincidenceofNoncommunicablediseases
suchasType2diabetes
MetabolicsyndromeObesity
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201511
Conception BirthFetaldevelopment Growth Adult
Noncommunicablediseasessuchas
Type2diabetesMetabolicsyndrome
Obesity
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201511
Conception BirthFetaldevelopment Growth Adult
Nutritionormetabolicstatusoftheparents
Obesity,undernutrition,diabetes…
Fetalgrowthadaptation
Epigenome,transcriptome,cells,tissues,organs
Noncommunicablediseasessuchas
Type2diabetesMetabolicsyndrome
Obesity
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201511
Conception BirthFetaldevelopment Growth Adult
NeonatalPhenotype
Nutritionormetabolicstatusoftheparents
Obesity,undernutrition,diabetes…
Fetalgrowthadaptation
Epigenome,transcriptome,cells,tissues,organs
Noncommunicablediseasessuchas
Type2diabetesMetabolicsyndrome
Obesity
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201512
UnitedNationsGeneralAssemblyinSeptember2011
“...maternalandchildhealthisinextricablylinkedwithNCDsandtheirriskfactors...”
(clause26)
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201513
CH Waddington 1905-1975
The Strategy of the Genes
1957
Molecularbasis:Epigenetics
“… stably maintained mitotically (and potentially meiotically) heritable patterns of gene expression that occur without changes in the DNA sequence”
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201513
CH Waddington 1905-1975
The Strategy of the Genes
1957
Molecularbasis:Epigenetics
“… stably maintained mitotically (and potentially meiotically) heritable patterns of gene expression that occur without changes in the DNA sequence”
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201513
CH Waddington 1905-1975
The Strategy of the Genes
1957
Molecularbasis:Epigenetics
“… stably maintained mitotically (and potentially meiotically) heritable patterns of gene expression that occur without changes in the DNA sequence”
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201517
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Maternal nutrition, post-natal catch-upand obesity in males
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201518
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Maternal nutrition, post-natal catch-upand obesity in males
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201519
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Maternal nutrition, post-natal catch-upand obesity in males
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201520
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Maternal nutrition, post-natal catch-upand obesity in males
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201521
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
-57%
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Maternal nutrition, post-natal catch-upand obesity in males
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201522
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Postnatalrestrictioncafeteria
Postnatalrestrictionbalanced
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria
Fetalgrowth?Placenta?
1stcriticalperiod"Actor"
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201523
8%
8% balanced
cafeteria 807±21
20%
20%
20%
20%
814±25
8%
8% 20%
20% balanced
cafeteria
568±36
517±35
Postnatalrestrictionbalanced
Postnatalrestrictioncafeteria
Inuterogrowthretardedbalanced
Inuterogrowthretardedcafeteria
Controlbalanced
Controlcafeteria 20%
20% balanced
cafeteria
765±22
715±21
OzanneandHales,Nature,2004
Gestation%proteins
Group Lactation%proteins
Post-weaning Lifespan(days)
Neonatalnutrition?Meanstoact?
2ndcriticalperiod"Revelator"
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
%fatmass
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201524
Dams OffspringControl Control High Fat High Fat
Control High Fat Control High Fat
Howie et al, J Physiol 2009
females males
%fatmass
- Offspring from obese females are predisposed to obesity - When exposed to an obesogenic environment, they develop a more severe phenotype
Role of maternal obesity in rats
Growthcurveofoffspring
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201525
Diet and obesity before conceptionRats: Obesogenic diet 3 weeks before conception then control diet during gestation and
lactation Offspring fed normal or high fat diet (HFD)
Shankar et al, 2008
Control/control Control/HFDMother/offspring
HFD/Control HFD/HFDMother/offspring
Maternal obesity before
conception can enhance offspring
response to a high fat diet
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201526
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
High fat/cholesterol diet (HH) = 6% soy oil +0.2% cholesterol
Control diet
Picone et al. 2011 Theriogenology
HH
C Components of the metabolic syndrome
in adults
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201527
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
High fat/cholesterol diet (HH) = 6% soy oil +0.2% cholesterol
Control diet
Intrauterine growth retardation from D9
Picone et al. 2011 Theriogenology
HH
C Components of the metabolic syndrome
in adults
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201528
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
High fat/cholesterol diet (HH) = 6% soy oil +0.2% cholesterol
Control diet
Intrauterine growth retardation from D9
Picone et al. 2011 Theriogenology
HH
C Components of the metabolic syndrome
in adults
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201529
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Tarrade et al. 2013 PloS One
Placental response in late gestation
C HH
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201530
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Tarrade et al. 2013 PloS One
Sexual dimorphism
⬈ Cholesterol esters
⬈ Triglycerides ⬈ Cholesterol esters
ì Fatty acid storage îLXRα
HH:î fatty acid and amino acid transporters
C HH
Severe dyslipidemia Mild dyslipidemiaFeto-placental response in late gestation
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201531
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Tarrade et al. 2013 PloS One
⬈ lipid droplets, Modifications of expression of fatty acid, glucose and amino acid transporters
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201532
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Picone et al. 2011 Theriogenology
8-16 cells Overexpression of adipophilin
Involved in lipid droplet formation At the onset of zygotic genome
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201533
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Delay in puberty î Number of follicles ì Follicular atresia
C HH
Cordier et al. 2013 PloS One
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201534
Rabbit model Diet supplemented in fat and cholesterol
10 w 12 w 18 w 22 wGestation
Puberty Reproduction Birth Weaning
26 wLactation
Delay in puberty î Number of follicles ì Follicular atresia
ì Follicular atresia
➘ Testicular weight ➘ Testosteronemia
C HH
Cordier et al. 2013 PloS One; Léveillé et al. 2014 J DOHAD; Dupont et al. 2014 J DOHAD.
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201535
Differentexposuresindifferentanimalmodels withsimilarcardiometabolicconsequences
Exposures
Energyrestriction
Proteinrestriction
Uterinearteryligation
Glucocorticoidexposure
Highfatdiet
Obesity
Diabetes
Small
Normal
Large
Outcomes
Hypertension
Insulinresistance
Glucoseintolerance
Increasedadiposity
Reducedmusclemass
Obesity
Type2Diabetes
Sizeatbirth
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201536
Aagaard-Tilleryetal,JMolEndocrinol2010
Maternaldietinducedobesitymodifiestheexpressionofenzymesinvolvedintheepigeneticmachinaryintheoffspringliver
Geneexpression
Protein
Enzymeactivity
D20BirthFertilizationD-3.5
18%
18%9%
Proteins(%ofcasein)
18%
Oo-LPD
Fertilization D20Birth
18%
18%
9%
9%
Proteins(%ofcasein)
18%
9%
Watkinsetal.,2008bWatkinsetal.,2008a
NPD
LPD
Embr-LPD
D3.5
Challenging different phases of the periconceptional period for their vulnerability to environmental changes:
Experimental Design in the mouse
D3.5-D3.5
39.
NPD
EmbryoLPD OocyteLPD
LPD during preimplantation development but not during oocyte maturation affects post-natal growth.
40.Watkinsetal.,2008bWatkinsetal.,2008a
EmbryoLPD OocyteLPD
LPD during preimplantation development but not during oocyte maturation affects post-natal growth.
40.Watkinsetal.,2008bWatkinsetal.,2008a
EmbryoLPD OocyteLPD
LPD during preimplantation development or during oocyte maturation leads to changes into postnatal behaviour.
41.
EmbryoLPD OocyteLPD
Inverse effects on behavior in response to open field test
Less stressed More stressed
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201541
Reducedexcessmaternalseruminflammation
Heerwagen et al, PloS One 2013
Dietary-inducedobeseC57BL/6JTransgeneFAT-1
Reducedplacentalinflammation
Interventionthroughmembraneremodeling
N-3fattyacids
Maternalseruminflammatorycytokines
Placentainflammatorycytokines
Conversionofn-6PUFAton-3
PUFAviaubiquitousn-3saturase
expression
Fetalweight
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201542
Reducingexcessmaternalinflammationmaybeapromisingtargetforpreventingadversefetalmetabolicoutcomesinpregnanciescomplicatedbymaternalobesity.
Heerwagen et al, PloS One 2013
Dietary-inducedobeseC57BL/6J
CD HFD
TransgeneFAT-1
InterventionthroughmembraneremodelingN-3fattyacids
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201543
Physicalexerciseandimprovementofmaternalbiologicalparameters
Nathanielszetal,NutrReviews2013
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201544
Physicalexerciseandimprovementofmaternalbiologicalparameters
Nathanielszetal,NutrReviews2013
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201545
Physicalexerciseandimprovementofmaternalbiologicalparameters
Nathanielszetal,NutrReviews2013
Bodyweight Fat Adipodityindex
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201546
Controversialoutcomesaftermaternalweightloss throughbariatricsurgerybeforeconception
Before maternal surgery N=54
After maternal surgery N=57
Kraletal,Pediatrics2006
Beforesurgery
Aftersurgery
Meanbirthweight(kg) 3.3+/-0.1 2.9+/-0.1 0.003Macrosomia(%) 14.8% 1.8% 0.03OffspringBMIpercentile(%) 79.4+/-3.4 68.4+/-4.0 0.04Offspringglycemia(mmol/l) 5.08+/-0.06 4.86+/-0.05 0.008
p
Smithetal,JCEM2009
UnderweightNormalOverweightObese UnderweightNormalOverweightObese
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201547
Before maternal surgery N=164
After maternal surgery N=176
Willmeretal,PloSOne2013
Controversialoutcomesaftermaternalweightloss throughbariatricsurgerybeforeconception
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201548
Animalexperimentationneeded!!!
Toevaluate/prevent- Risksofvitaminicdeficiency- Risksoffetaldenutrition- Evaluatepost-surgicalperiods
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201550
Birth Genome activation
ImplantationOrganogenesis
Gonadal differntiation
Stages of development
Placental function
Suckling
Maternalnutritionandenvironment
Sexspecificconditioningleadingtopathologies
Puberty
TakeHomemessage1:Criticalperiodsandsexualdimorphism
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201551
DeVinci/1510
TakeHomemessage2:Animalmodelsareessentialbutcanbedifferent
Bewareofmouseas«the»Animal
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201551
DeVinci/1510
TakeHomemessage2:Animalmodelsareessentialbutcanbedifferent
Bewareofmouseas«the»Animal
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201552
DeVinci/1510
TakeHomemessage2:Animalmodelsareessentialbutcanbedifferent
Bewareofmouseas«the»AnimalWatchout!
Miceisnotthebestmodel…
Embryonic,gestationalandpost-natalmetabolismdifferlargelyfromhumans…
Proofsfromseveralmodelsarenecessary!
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201552
DeVinci/1510
TakeHomemessage2:Animalmodelsareessentialbutcanbedifferent
Bewareofmouseas«the»AnimalWatchout!
Miceisnotthebestmodel…
Embryonic,gestationalandpost-natalmetabolismdifferlargelyfromhumans…
Proofsfromseveralmodelsarenecessary!
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201553
Theenvironmentaffectsthemother(F0)1
TakeHomemessage3:Severalgenerationscanbeaffected
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201554
Theenvironmentaffectsthemother(F0)1
Theplacentaregulatesfetalintakeandthefetus(F1)adaptsitsmetabolismthroughepigeneticmodifications,withsexspecificdifferences
2
TakeHomemessage3:Severalgenerationscanbeaffected
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201555
Theenvironmentaffectsthemother(F0)1
3Gonadaldevelopmentand
fetalgametescanbeaffected,thusinducingeffectsonfertilityandon
secondgenerationoffspring(F2)
Theplacentaregulatesfetalintakeandthefetus(F1)adaptsitsmetabolismthroughepigeneticmodifications,withsexspecificdifferences
2
TakeHomemessage3:Severalgenerationscanbeaffected
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201556
Theenvironmentaffectsthemother(F0)1
3Gonadaldevelopmentand
fetalgametescanbeaffected,thusinducingeffectsonfertilityandon
secondgenerationoffspring(F2)
Theplacentaregulatesfetalintakeandthefetus(F1)adaptsitsmetabolismthroughepigeneticmodifications,withsexspecificdifferences
2
4Epigeneticmodificationpersistinginthegermlinecaninducetrasngenerationaleffects(F>2
TakeHomemessage3:Severalgenerationscanbeaffected
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201557
Theenvironmentaffectsthemother(F0)1
3Gonadaldevelopmentand
fetalgametescanbeaffected,thusinducingeffectsonfertilityandon
secondgenerationoffspring(F2)
Theplacentaregulatesfetalintakeandthefetus(F1)adaptsitsmetabolismthroughepigeneticmodifications,withsexspecificdifferences
2
4Epigeneticmodificationpersistinginthegermlinecaninducetrasngenerationaleffects(F>2
…andthefather
TakeHomemessage3:alsothroughmales
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201558
Before maternal surgery N=54
After maternal surgery N=57
Meanbirthweight(kg) 3.3+/-0.1 2.9+/-0.1 0.003Macrosomia(%) 14.8% 1.8% 0.03OffspringBMIpercentile(%) 79.4+/-3.4 68.4+/-4.0 0.04Offspringglycemia(mmol/l) 5.08+/-0.06 4.86+/-0.05 0.008
p
Smithetal,JCEM2009
Improvementofchildrenoutcomesaftermaternalweightloss throughbariatricsurgerybeforeconception
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201559
Plasticity
↑risksofdevelopingpathologies
Earlyintervention
Littleimpactinadulthood
TakeHomemessage4:Earlyinterventionwillhelp
Forexhaustivereview:HansonandGluckman2014,PhysRev,94:1027-1076
1000daystoact,anWHOinitiative
Nutritional,ecological,psychological,socio-economical
environment
2years(http://www.thousanddays.org/)
1000daystoact,anWHOinitiative
Nutritional,ecological,psychological,socio-economical
environment
2years
->nottoforgetthefatherandtransgenerationaleffects«100yearsofdevelopment»
(http://www.thousanddays.org/)
Pascale CHAVATTE-PALMER / PIANETANUTRIZION 25/06/201561
PEPPSteam:Placenta,EnvironmentandProgrammingofPhenotypeS
Thankyou
pascale.chavatte@jouy.inra.fr