Developmental Programming in Livestock: Why Maternal ... · Trt: P = 0.04 Day*trt: P = 0.14 o od...

Developmental ProgrammingDevelopmental Programmingin Livestock:

Why Maternal Nutrition Impacts MoreWhy Maternal Nutrition Impacts MoreThan Just the Dam

Kimberly Vonnahme, PhDAssociate ProfessorAssociate Professor

Department of Animal Sciences

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

AcknowledgementsAcknowledgements• Collaborators at NDSU

– Kendall SwansonJoel Caton

• Students and Staff– Bethany Mordhorst– Arshi Reyaz– Joel Caton

– Christopher Schauer– Steve O’Rourke– Larry Reynolds– Dale Redmer

Arshi Reyaz– Leslie Lekatz– Leticia Camacho– Erin Harris– Breanne Ilse

Allison Meyer– Anna Grazul-Bilska– Justin Luther– Carrie Hammer– Greg Lardy– Kasey Carlin

– Allison Meyer– Tammi Neville– Jim Kirsch– Jake Reed

Kasey Carlin– Eric Berg

• Other collaborators– Rick Funston—UNL

B T l USDA ARS– Bret Taylor—USDA-ARS SES

– Caleb Lemley– MSU NDSU Animal Nutrition and Physiology Center


OUTLINEOUTLINE

• What is developmental programming?What is developmental programming?

• What is happening at NDSU…– A reproductive biologist’s perspective…

Understanding the biology– Understanding the biology….– Can we come up with tools to help….


PhenotypePhenotype

Phenotype = Genotype + EnvironmentClassic Animal Breeding Example

Phenotype Genotype + EnvironmentEg. Milk production = Holstein genetics + Mastitis


PhenotypePhenotypeFuture Animal Breeding Exampleg p

Phenotype = Genotype + EnvironmentEg Yield grade = Angus genetics + Uterine environmentEg. Yield grade = Angus genetics + Uterine environment


ProgrammingProgramming

• The process through which a stimulus or insultThe process through which a stimulus or insultestablishes a permanent response

• Developmental programming hypothesis• Exposure during a critical period in developmentExposure during a critical period in development

may influence later metabolic or physiological functions in adult life


Developmental (Fetal) P iProgramming

• Also known as the “Barker Hypothesis”Also known as the Barker Hypothesis• Dr. David Barker Epidemiological

InformationInformation

Clinical Research

AnimalResearch


The Dutch Hunger WinterSeptember 1944 - May 1945


STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYVonnahme, March 2008

Incidence of adult obesity in the hild f th D t h H Wi t

3children of the Dutch Hunger Winter

2 % of babies who becomeobese as adults

2

obese as adults1

01 2

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYNone1 Last third First two thirds None2

10 PRINCIPLES OF DEVELOPMENTAL PROGRAMMINGPROGRAMMING

1) During development in the womb, there are critical periods of vulnerability to suboptimal conditions.

Vulnerable periods occur at different times for differentdifferent times for different tissues.


“TIMING IS EVERYTHING”



5) The placenta plays a key role in programming.


SHEEP AND COW PLACENTASSHEEP AND COW PLACENTAS



6) Compensation carries a price. In an unfavorable penvironment, the developing baby makes attempts to compensate for deficiencies. However the compensatoryHowever, the compensatory effort often carries a price.


Mechanisms of Programming?Mechanisms of Programming?Nutritional Influence

Altered cell number orintracellular organization

Reorganisation of organ structureMetabolic Differentiation

DNA Control?g gAbnormal early cell-cell interactions?

DNA Control?(altered cell specific gene regulation)

DNA Environment?(altered DNA binding proteins)

Al d DNA h l i ?STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

Altered DNA methylation?

EpigeneticsEpigeneticsThe study of changes y gin gene expression or cellular phenotype, caused bycaused by mechanisms other than changes in the

d l i DNAunderlying DNA sequence


How does epigenetics fit into selection?

DNAEpigenetics

DNAEPD


What’s HappeningWhat s Happening at NDSU?

“Healthy Offspring through Optimal Nutrition”

North Dakota State UniversityCollege of Agriculture, Food Systems, College of Agriculture, Food Systems,

and Natural ResourcesFargo, ND 58105-5727


Global Nutrition and SeleniumGlobal Nutrition and Selenium


NDSU Sheep StudiesNDSU Sheep Studies

HighSelenium (n=14) 100% NRC

(n=14) 140% NRC

(n=42)

Breedingt 50dGA Parturition

(n=14) 60% NRC (n=81) All lambs placed on identical

nutrition scheme until market weighth f b hto 50dGA Parturition

(n 13) 100% NRCNormalS l i

48 h after birth to weaning = Bucket Teat Unit

Weaning to Market(n=13) 140% NRC

(n=13) 100% NRC

(n=14) 60% NRC

Selenium(n=40)


Maternal intake and BW changesMaternal intake and BW changes*Se – NSDiet P<0 01

75

8060% NRC100% NRC

Diet – P<0.01, (d90‐145, all diets differ)

t, kg

65

70140% NRC

Wei

ght

55

60

45

50

55

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYDay of gestation

40 60 80 100 120 140 16045

5 Males Nut*sex; P = 0.02kg

4

5 MalesFemales

ab

ac acc

ab

;th

wei

ght,

2

3

Birt

1

2

Maternal nutritional intakeRES CON HIGH

0

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYMaternal nutritional intake

2500

1500

2000

(mg/

dl) Nutr. X Se;

P < 0.05

1000

erum

IgG

0

500Se

RES (60%) CON (100%) HIGH (140%)

A Se H Se


Hammer et al., 2011

9

7

8

bs)

5

6

of L

amb

3

4

rtal

ity (#

1

2Mor

0RES (60%) CON (100%) HIGH (140%)

Hammer et al., 2011P < 0.02

To 6 months of age

• Increased growth of females that wereIncreased growth of females that were restricted

• Increased proliferation rate of ovaries• Increased proliferation rate of ovaries in female lambs from ASe-CON N diff i i ht• No differences in carcass weight

• HSe maternal diets may have been beneficial in terms of carcass


Can Melatonin Help?Can Melatonin Help?


Doppler UltrasonographyDoppler Ultrasonography


Umbilical Blood FlowUmbilical Blood Flow m

in 500 *F,

mL/

m

300

400ADQ (n = 15)RES (n = 16)

*

ical

BF

200

300

**

Um

bili

0

100Nut*Day; P < 0.0001

Gestation, d40 50 60 70 80 90 100 110

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYLemley et al., 2012

Umbilical Blood FlowUmbilical Blood Flowin CON-RES (n = 8)

mL/

mi

400

500 CON RES (n = 8)CON-ADQ (n = 7)MEL-RES (n = 8)MEL-ADQ (n = 8)

al B

F,

200

300 Trt*Nut*Day; P = 0.15

mbi

lica

0

100

Gestation, d40 50 60 70 80 90 100 110

U


,

Lemley et al. (2012) AJP.

Instantaneous growth rate of the bovine fetus

0.4

0.3

Kg/d

ay

0.2

0.1

0 0

Day of gestation

50 100 150 200 250 3000.0

When do I need to intervene?


Percentage NRC recommendations

100%

100% (n=6)

60% (n=6)

100%

100% 100%

(n=18)60% (n=6) 60%

d 0 d 30 d 85 d 140 d 260

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY5/2/2013

Things that make you go HHmmmmm….

Day 85 Control Restricted SEM P-valueDay 85 Control Restricted SEM P-valueFetal wt, g 116.9 138.9 8.0 0.07CRL, cm 17.0 17.0 0.01 0.28Girth, cm 10.3 10.8 0.16 0.04Placental wt, g

84.8 118.7 5.9 0.002

Placentome # 45.7 68.4 6.2 0.02The placenta of the cow adapts very

l t t l120

140

early to maternal nutrient restriction… how will this impact her fetus after birth?

% re

laxa

tion

40

60

80

100

CONTROLRESTRICTED

Trt: P = 0.02Dose: P = < 0.01Trt*Dose: P < 0.01

Dose

1e-10 1e-9 1e-8 1e-7 1e-6 1e-5 1e-420

RESTRICTED

Blood flow DataBlood flow DataPreliminary look at uterine blood flow

ml/m

in

40

45

50Day: P = 0.10Trt: P = 0.04Day*trt: P = 0.14

ood

flow

,

30

35

40

terin

e bl

o

20

25

30

Control throughoutRestricted to d 85 then control

Day of gestation200 210 220 230 240 250

Ut

15

Restricted to d 85, then controlRestricted to d 140, then control

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITYDay of gestation

What about early blood flow?What about early blood flow?


Fig. 9-10

Senger text

L/m

in

12

14

16 CONRES

arte

ry B

F,

8

10

12

eral

ute

rine

4

6

8

Restriction

Ipsi

late

0

2

4

Treatment×day×period; P = 0.99Treatment*period; P = 0.02

Gestation, d

40 60 80 100 120 140 160 180 200


6 CON

BF,

L/m

in4

RES

ne a

rtery

B 4at

eral

ute

rin

2 Restriction

Con

trala

0Treatment×day×period; P = 0.06Treatment*period; P = 0.06

Gestation, d

40 60 80 100 120 140 160 180 200


20

min

15

20CONRES

tery

BF,

L/m

10

15

ute

rine

art

5

10

Restriction

Tota

l

0

5

Treatment×day×period; P = 0.98

Gestation, d

40 60 80 100 120 140 160 180 200

0


Protein Supplementation During L PLate Pregnancy

Impacts on female progeny p g yreproductive success

• Martin et al., 2008


Reproductive PerformanceReproductive Performance Treatment

Item Prot NoProt SEM P-value

Age at Puberty d 339 334 10 0 70Age at Puberty, d 339 334 10 0.70

Cycling at beginning of breeding season, % 61 67 - 0.45

Calved in first 21 d, % 77 49 - 0.005

Overall pregnancy rate, % 93 80 - 0.05

Calving date Julian d 71 75 3 0 15Calving date, Julian d 71 75 3 0.15

Calf birth wt, kg 33 33 1 0.94

Unassisted births, % 78 64 - 0.24


Protein influence on uterine blood flowProtein influence on uterine blood flow


MP during Last Third of Gestation in Ewes


Don’t Just Blame Your Mom!Don t Just Blame Your Mom!

• Research studies performed in rodentsResearch studies performed in rodents– Drugs– CarcinogensCarcinogens– Environmental estrogens (BPA)

• Conclusions: Dad can impact fetal development• Conclusions: Dad can impact fetal development• Work in livestock is largely lacking


Future DirectionsFuture Directions

• Time period of supplementationTime period of supplementation• Specific nutrients that are important

M t l ffi i i d t l• Maternal efficiencies and maternal age • Factors that impact

– Uterine and placental blood flow– Mammary gland developmenty g p


Developmental ProgrammingDevelopmental Programming

• IMPORTANT TO ANIMAL HEALTH• IMPORTANT TO ANIMAL HEALTH AND PRODUCTIVITY:–Growth and nutrient transfer–Reproductive capacityp p y–Aging and lifetime productivity


Goal: Healthy Offspring!!!Goal: Healthy Offspring!!!


AcknowledgementsAcknowledgements

NDSU Animal Nutrition and Ph i l C tPhysiology Center

Developmental Programming in Livestock: Why Maternal ... · Trt: P = 0.04 Day*trt: P = 0.14 o od...

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