Developmental Programming Developmental Programming in Livestock: - - PowerPoint PPT Presentation

▶
developmental programming developmental programming in
SMART_READER_LITE
LIVE PREVIEW

Developmental Programming Developmental Programming in Livestock: - - PowerPoint PPT Presentation

Mar 03, 2023 12 likes •623 views

Developmental Programming Developmental Programming in Livestock: Why Maternal Nutrition Impacts More Why Maternal Nutrition Impacts More Than Just the Dam Kimberly Vonnahme, PhD Associate Professor Associate Professor Department of Animal

slide-1
SLIDE 1
slide-2
SLIDE 2

Developmental Programming Developmental Programming in Livestock: Why Maternal Nutrition Impacts More Why Maternal Nutrition Impacts More Than Just the Dam Kimberly Vonnahme, PhD Associate Professor Associate Professor Department of Animal Sciences

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-3
SLIDE 3

Acknowledgements Acknowledgements

  • Collaborators at NDSU

– Kendall Swanson Joel 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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-4
SLIDE 4

OUTLINE OUTLINE

  • 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….

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-5
SLIDE 5

Phenotype Phenotype

Phenotype = Genotype + Environment

Classic Animal Breeding Example

Phenotype Genotype + Environment

  • Eg. Milk production = Holstein genetics + Mastitis

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-6
SLIDE 6

Phenotype Phenotype

Future Animal Breeding Example g p

Phenotype = Genotype + Environment

Eg Yield grade = Angus genetics + Uterine environment

  • Eg. Yield grade = Angus genetics + Uterine environment

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-7
SLIDE 7

Programming Programming

  • The process through which a stimulus or insult

The process through which a stimulus or insult establishes a permanent response

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

Exposure during a critical period in development may influence later metabolic or physiological functions in adult life

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-8
SLIDE 8

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-9
SLIDE 9

Developmental (Fetal) P i Programming

  • Also known as the “Barker Hypothesis”

Also known as the Barker Hypothesis

  • Dr. David Barker

Epidemiological Information Information Clinical Research Animal Research

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-10
SLIDE 10

The Dutch Hunger Winter September 1944 - May 1945

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-11
SLIDE 11

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

Vonnahme, March 2008

slide-12
SLIDE 12
slide-13
SLIDE 13

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

3

children of the Dutch Hunger Winter

2

% of babies who become

  • bese as adults

2

  • bese as adults

1

1 2

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

None

1 Last third First two thirds None 2

slide-14
SLIDE 14

10 PRINCIPLES OF DEVELOPMENTAL PROGRAMMING PROGRAMMING

1) During development in the womb, there are critical periods of vulnerability to suboptimal conditions. Vulnerable periods occur at different times for different different times for different tissues.

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-15
SLIDE 15

“TIMING IS EVERYTHING”

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-16
SLIDE 16

10 PRINCIPLES OF DEVELOPMENTAL PROGRAMMING PROGRAMMING

5) The placenta plays a key role in programming.

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-17
SLIDE 17

SHEEP AND COW PLACENTAS SHEEP AND COW PLACENTAS

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-18
SLIDE 18

10 PRINCIPLES OF DEVELOPMENTAL PROGRAMMING PROGRAMMING

6) Compensation carries a

  • price. In an unfavorable

p environment, the developing baby makes attempts to compensate for deficiencies. However the compensatory However, the compensatory effort often carries a price.

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-19
SLIDE 19

?

slide-20
SLIDE 20

?

slide-21
SLIDE 21

Mechanisms of Programming? Mechanisms of Programming?

Nutritional Influence

Altered cell number or intracellular organization Reorganisation of organ structure Metabolic Differentiation DNA Control? g g Abnormal 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?

slide-22
SLIDE 22

Epigenetics Epigenetics

The study of changes y g in gene expression or cellular phenotype, caused by caused by mechanisms other than changes in the d l i DNA underlying DNA sequence

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-23
SLIDE 23

How does epigenetics fit into selection?

DNA

Epigenetics

DNA

EPD

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-24
SLIDE 24

What’s Happening What s Happening at NDSU?

“Healthy Offspring through Optimal Nutrition”

North Dakota State University College of Agriculture, Food Systems, College of Agriculture, Food Systems, and Natural Resources Fargo, ND 58105-5727

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-25
SLIDE 25

Global Nutrition and Selenium Global Nutrition and Selenium

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-26
SLIDE 26

NDSU Sheep Studies NDSU Sheep Studies

High Selenium

(n=14) 100% NRC (n=14) 140% NRC

(n=42)

Breeding t 50dGA

Parturition

(n=14) 60% NRC

(n=81) All lambs placed on identical nutrition scheme until market weight h f b h

to 50dGA

Parturition

(n 13) 100% NRC

Normal S 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) STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-27
SLIDE 27

Maternal intake and BW changes Maternal intake and BW changes

*Se – NS Diet P<0 01

75 80 60% NRC 100% NRC

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

t, kg

65 70 140% NRC

Weight

55 60 45 50 55

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

Day of gestation

40 60 80 100 120 140 160 45

slide-28
SLIDE 28

5 Males Nut*sex; P = 0.02

kg

4 5 Males Females a b ac ac c ab ;

th weight,

2 3

Birt

1 2

Maternal nutritional intake

RES CON HIGH

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

Maternal nutritional intake

slide-29
SLIDE 29

2500 1500 2000 (mg/dl)

  • Nutr. X Se;

P < 0.05 1000 erum IgG 500 Se RES (60%) CON (100%) HIGH (140%) A Se H Se STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Hammer et al., 2011

slide-30
SLIDE 30

9 7 8 bs) 5 6

  • f Lamb

3 4 rtality (# 1 2 Mor RES (60%) CON (100%) HIGH (140%)

Hammer et al., 2011 P < 0.02

slide-31
SLIDE 31

To 6 months of age

  • Increased growth of females that were

Increased 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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-32
SLIDE 32

Can Melatonin Help? Can Melatonin Help?

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-33
SLIDE 33

Doppler Ultrasonography Doppler Ultrasonography

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-34
SLIDE 34

Doppler Ultrasonography Doppler Ultrasonography

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-35
SLIDE 35

Umbilical Blood Flow Umbilical Blood Flow

min

500

*

F, mL/m

300 400

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

*

ical BF

200 300

* *

Umbili

100

Nut*Day; P < 0.0001

Gestation, d

40 50 60 70 80 90 100 110

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Lemley et al., 2012

slide-36
SLIDE 36

Umbilical Blood Flow Umbilical Blood Flow

in

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 BF,

200 300

Trt*Nut*Day; P = 0.15

mbilica

100

Gestation, d

40 50 60 70 80 90 100 110

U

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

,

Lemley et al. (2012) AJP.

slide-37
SLIDE 37

Instantaneous growth rate of the bovine fetus

0.4 0.3 Kg/day 0.2 0.1 0 0 Day of gestation 50 100 150 200 250 300 0.0

slide-38
SLIDE 38

When do I need to intervene?

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-39
SLIDE 39

Percentage NRC Percentage NRC recommendations recommendations 100% 100%

100% (n=6) 100% (n=6) 60% (n=6) 60% (n=6) 100% 100% 100% 100% 100% 100%

(n=18) (n=18)

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

d 0 d 0 d 30 d 30 d 85 d 85 d 140 d 140 d 260 d 260 STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

5/2/2013

slide-40
SLIDE 40

Things that make you go Hmmmmm….

Day 85 Control Restricted SEM P-value Day 85 Control Restricted SEM P-value Fetal wt, g 116.9 138.9 8.0 0.07 CRL, cm 17.0 17.0 0.01 0.28 Girth, cm 10.3 10.8 0.16 0.04 Placental wt, g 84.8 118.7 5.9 0.002 Placentome # 45.7 68.4 6.2 0.02 The placenta of the cow adapts very l t t l

120 140

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

% relaxation 40 60 80 100 CONTROL RESTRICTED Trt: P = 0.02 Dose: P = < 0.01 Trt*Dose: P < 0.01 Dose 1e-10 1e-9 1e-8 1e-7 1e-6 1e-5 1e-4 20 RESTRICTED
slide-41
SLIDE 41

Blood flow Data Blood flow Data

Preliminary look at uterine blood flow

ml/min

40 45 50 Day: P = 0.10 Trt: P = 0.04 Day*trt: P = 0.14

  • od flow,

30 35 40

terine blo

20 25 30

Control throughout Restricted to d 85 then control

Day of gestation

200 210 220 230 240 250

Ut

15

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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

Day of gestation

slide-42
SLIDE 42

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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-43
SLIDE 43
  • Fig. 9-10

Senger text

slide-44
SLIDE 44

L/min

12 14 16 CON RES

artery BF,

8 10 12

eral uterine

4 6 8

Restriction Ipsilate

2 4

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

Gestation, d

40 60 80 100 120 140 160 180 200

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-45
SLIDE 45

6 CON

BF, L/min

4 RES

ne artery B

4

ateral uterin

2

Restriction

Contrala

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

Gestation, d

40 60 80 100 120 140 160 180 200

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-46
SLIDE 46

20

min

15 20 CON RES

tery BF, L/m

10 15

uterine art

5 10

Restriction Total

5

Treatment×day×period; P = 0.98

Gestation, d

40 60 80 100 120 140 160 180 200

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-47
SLIDE 47
slide-48
SLIDE 48

Protein Supplementation During L P Late Pregnancy

Impacts on female progeny p g y reproductive success

  • Martin et al., 2008

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-49
SLIDE 49

Reproductive Performance Reproductive Performance

Treatment Item Prot NoProt SEM P-value Age at Puberty d 339 334 10 0 70 Age 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 15 Calving date, Julian d 71 75 3 0.15 Calf birth wt, kg 33 33 1 0.94 Unassisted births, % 78 64

  • 0.24

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-50
SLIDE 50

Reproductive Performance Reproductive Performance

Treatment Item Prot NoProt SEM P-value Age at Puberty d 339 334 10 0 70 Age 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 15 Calving date, Julian d 71 75 3 0.15 Calf birth wt, kg 33 33 1 0.94 Unassisted births, % 78 64

  • 0.24

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-51
SLIDE 51

Protein influence on uterine blood flow Protein influence on uterine blood flow

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-52
SLIDE 52

Protein influence on uterine blood flow Protein influence on uterine blood flow

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-53
SLIDE 53

Protein influence on uterine blood flow Protein influence on uterine blood flow

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-54
SLIDE 54

MP during Last Third of Gestation in Ewes

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-55
SLIDE 55
slide-56
SLIDE 56

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

  • Research studies performed in rodents

Research studies performed in rodents – Drugs – Carcinogens Carcinogens – Environmental estrogens (BPA)

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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-57
SLIDE 57

Future Directions Future Directions

  • Time period of supplementation

Time 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 development y g p

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-58
SLIDE 58

Developmental Programming Developmental Programming

  • IMPORTANT TO ANIMAL HEALTH
  • IMPORTANT TO ANIMAL HEALTH

AND PRODUCTIVITY:

–Growth and nutrient transfer –Reproductive capacity p p y –Aging and lifetime productivity

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-59
SLIDE 59

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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-60
SLIDE 60

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

STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY

slide-61
SLIDE 61

Acknowledgements Acknowledgements

NDSU Animal Nutrition and Ph i l C t Physiology Center