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
Acknowledgements Acknowledgements • Students and Staff • Collaborators at NDSU – Bethany Mordhorst – Kendall Swanson – Arshi Reyaz Arshi Reyaz – Joel Caton Joel Caton – Leslie Lekatz – Christopher Schauer – Leticia Camacho – Steve O’Rourke – Erin Harris – Larry Reynolds – Breanne Ilse – Dale Redmer – Allison Meyer Allison Meyer – Anna Grazul-Bilska – Tammi Neville – Justin Luther – Jim Kirsch – Carrie Hammer – Jake Reed – Greg Lardy – Kasey Carlin Kasey Carlin – Eric Berg • Other collaborators – Rick Funston—UNL – Bret Taylor—USDA-ARS B T l USDA ARS SES NDSU Animal Nutrition and – Caleb Lemley– MSU Physiology Center STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
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
Phenotype Phenotype Classic Animal Breeding Example Phenotype = Genotype + Environment Phenotype Genotype + Environment Eg. Milk production = Holstein genetics + Mastitis STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
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
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
STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Developmental (Fetal) P Programming i • Also known as the “Barker Hypothesis” Also known as the Barker Hypothesis • Dr. David Barker Epidemiological Information Information Animal Clinical Research Research STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
The Dutch Hunger Winter September 1944 - May 1945 STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Vonnahme, March 2008
Incidence of adult obesity in the children of the Dutch Hunger Winter hild f th D t h H Wi t 3 2 2 % of babies who become obese as adults obese as adults 1 0 1 1 Last third First two thirds None 2 2 None STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
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
“T IMING IS E VERYTHING ” STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
10 PRINCIPLES OF DEVELOPMENTAL PROGRAMMING PROGRAMMING 5) The placenta plays a key role in programming. STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
SHEEP AND COW PLACENTAS SHEEP AND COW PLACENTAS STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
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
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Mechanisms of Programming? Mechanisms of Programming? Nutritional Influence Altered cell number or intracellular organization Metabolic Differentiation Reorganisation of organ structure g g DNA Control? DNA Control? Abnormal early cell-cell interactions? (altered cell specific gene regulation) DNA Environment? (altered DNA binding proteins) Al Altered DNA methylation? d DNA h l i ? STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Epigenetics Epigenetics The study of changes y g in gene expression or cellular phenotype, caused by caused by mechanisms other than changes in the underlying DNA d l i DNA sequence STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
How does epigenetics fit into selection? Epigenetics DNA DNA EPD STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
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
Global Nutrition and Selenium Global Nutrition and Selenium STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
NDSU Sheep Studies NDSU Sheep Studies (n=14) 140% NRC High (n=14) 100% NRC Selenium (n=42) (n=14) 60% NRC (n=81) All lambs placed on identical nutrition scheme until market weight Breeding Parturition Parturition t 50dGA to 50dGA 48 h after birth to weaning = h f b h Bucket Teat Unit Weaning to Market (n=13) 140% NRC Normal (n 13) 100% NRC (n=13) 100% NRC S l Selenium i (n=40) (n=14) 60% NRC STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Maternal intake and BW changes Maternal intake and BW changes *Se – NS Diet Diet – P<0.01, P<0 01 (d90 ‐ 145, all 80 diets differ) 60% NRC 75 100% NRC 140% NRC 70 t, kg 65 Weight 60 55 55 50 45 45 40 60 80 100 120 140 160 STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Day of gestation
Nut*sex; P = 0.02 ; Males Males 5 5 c Females ac ac a 4 ab kg b th weight, 3 2 2 Birt 1 0 RES CON HIGH Maternal nutritional intake Maternal nutritional intake STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
2500 2000 Nutr. X Se; (mg/dl) P < 0.05 1500 erum IgG 1000 Se 500 0 RES (60%) CON (100%) HIGH (140%) A Se H Se STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Hammer et al., 2011
9 8 7 bs) of Lamb 6 5 rtality (# 4 3 Mor 2 1 0 P < 0.02 RES (60%) CON (100%) HIGH (140%) Hammer et al., 2011
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 • No differences in carcass weight N diff i i ht • HSe maternal diets may have been beneficial in terms of carcass STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Can Melatonin Help? Can Melatonin Help? STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Doppler Ultrasonography Doppler Ultrasonography STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Doppler Ultrasonography Doppler Ultrasonography STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Umbilical Blood Flow Umbilical Blood Flow min * 500 F, mL/m ADQ (n = 15) RES (n = 16) 400 * ical BF 300 300 * * 200 Umbili 100 Nut*Day; P < 0.0001 0 40 50 60 70 80 90 100 110 Gestation, d STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Lemley et al., 2012
Umbilical Blood Flow Umbilical Blood Flow in CON-RES (n = 8) CON RES (n = 8) mL/mi 500 CON-ADQ (n = 7) MEL-RES (n = 8) 400 MEL-ADQ (n = 8) al BF, 300 Trt*Nut*Day; P = 0.15 200 mbilica 100 0 U 40 50 60 70 80 90 100 110 Gestation, d , STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY Lemley et al. (2012) AJP.
Instantaneous growth rate of the bovine fetus 0.4 0.3 Kg/day 0.2 0.1 0 0 0.0 50 100 150 200 250 300 Day of gestation
When do I need to intervene? STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY
Percentage NRC Percentage NRC recommendations recommendations 100% 100% 100% (n=6) 100% (n=6) 100% 100% 60% (n=6) 60% (n=6) 100% 100% 100% 100% (n=18) (n=18) 60% (n=6) 60% (n=6) 60% 60% d 30 d 30 d 0 d 0 d 85 d 85 d 140 d 140 d 260 d 260 STUDENT FOCUSED • LAND GRANT • RESEARCH UNIVERSITY 5/2/2013
Things that make you go Hmmmmm…. Day 85 Day 85 Control Control Restricted Restricted SEM SEM P-value 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, 84.8 118.7 5.9 0.002 g Placentome # 45.7 68.4 6.2 0.02 The placenta of the 140 cow adapts very 120 early to maternal l t t l 100 relaxation nutrient restriction… 80 Trt: P = 0.02 Dose: P = < 0.01 % how will this impact Trt*Dose: P < 0.01 60 her fetus after birth? CONTROL 40 RESTRICTED RESTRICTED 20 1e-10 1e-9 1e-8 1e-7 1e-6 1e-5 1e-4 Dose
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