Mother’s eating habits affect her daughters’ milk production Professor Hugh Blair et al IVABS, International Sheep Research Centre and NRCGD, Massey University
A bit of history Lamarck (c.1800) inheritance of acquired characters (antelopes → giraffes) Hammond (1930s-50s) maternal constraint (crossing Shire horses & Shetland ponies) Lysenko (1940s-50s) inheritance of vernalisation (increased grain yields) Waddington (1940s-50s) epigenetic landscape & canalisation ( plasticity ) Lush (1940s) repeatability; permanent environmental effects
A bit of history Barker (1980s-90s) Barker hypothesis, thrifty phenotype, Developmental Origins of Health and Disease (DOHaD), fetal programming Morgan, Sutherland, Martin & Whitelaw (1999) epigenetic inheritance in mice Gluckman & Hanson (2000s) predictive adaptive response mismatch
Birth weight and CHD (Keith Godfrey and David Barker) FIGURE 1. Coronary heart disease death rates, expressed as standardized mortality ratios, in 10141 men and 5585 women born in Hertfordshire, United Kingdom, from 1911 to 1930, according to birth weight. Derived from Osmond et al (12). American Journal of Clinical Nutrition, Vol. 71, No. 5, 1344S-1352s, May 2000
A bit of history Barker (1980s-90s) Barker hypothesis, thrifty phenotype, Developmental Origins of Health and Disease (DOHaD), fetal programming Morgan, Sutherland, Martin & Whitelaw (1999) epigenetic inheritance in mice Gluckman & Hanson (2000s) predictive adaptive response mismatch
Folic acid and obesity / colour
A bit of history Barker (1980s-90s) Barker hypothesis, thrifty phenotype, Developmental Origins of Health and Disease (DOHaD), fetal programming Morgan, Sutherland, Martin & Whitelaw (1999) epigenetic inheritance in mice Gluckman & Hanson (2000s) predictive adaptive response mismatch
Fetal programming “Programming” of metabolism / physiology to match predicted environment behavioural responses to improve survival etc Probably via epigenetic mechanisms
Why? enhanced survival (short-term – plasticity) improved chance of gene(s) being passed to the next generation evolution (long-term)?
Several animal/insect models Southampton – protein restriction in mice Auckland – calorific restriction in rats McGill – grooming rats Otago – honey bees Massey – sheep
Massey sheep research Fetal programming and its importance for farm animals How do stressors during pregnancy affect later life performance? Is this transmitted between generations?
What sort of stressors? Restricted feeding during pregnancy Genetic maternal constraint Young growing pregnant mothers Multiple fetuses
What drives us? Identification of economically relevant effects of fetal programming in farm animals Development of a cost-effective measurement tool Development of interventions either manipulation of animal biology or culling of animals predicted to perform poorly in their lifetime
2005 pregnancy feeding trial
Feed restriction d21-140 Synchronized AI Suffolk semen D21 – D140 of pregnancy Ad libitum (84kg) Maintenance (70kg)
Feed restriction After birth At 2 years of age After weaning Synchronized & Mated All offspring treated the same post-d140 of pregnancy
G1 Ewes born to ad libitum fed dams ** P<0.05 G1 Ewes born to maintenance fed dams * P<0.10 3.5 5.5 ** ** 5.4 3 * Milk yield (kg) 5.3 Lactose % 2.5 5.2 2 5.1 1.5 5 0 0 7 14 21 28 35 42 49 7 14 21 28 35 42 49 Days in lactation Days in lactation
2009 pregnancy feeding trial
Study designed to: • Identify critical programming periods • Identify optimal maternal feeding conditions • Identify potential mechanisms
Dam (G0) weights Preg50 Preg137 Lact91 Treatment kg ( ±0.5 ) kg ( ±0.6) kg ( ±0.7) L20-50 84.3 70.2 62.2 a M20-50 85.5 70.6 65.1 b H20-50 69.5 c 86.4 72.2 M51-140 82.6 a 71.7 H51-140 88.2 b 70.3
Effect of dam (G0) nutrition during pregnancy (P20 – 140) on adult ewe offspring (G1) live weight from mating 90.0 parturition 85.0 HH HM 80.0 LH LM PD MH 75.0 MM Live weight mating (kg) 70.0 weaning 65.0 60.0 docking 55.0 550 600 650 700 750 800 850 Age (days)
Effect of dam nutrition during pregnancy (P20 – 140) 3700 on offspring milk yields 3200 HH HM LH 2700 LM Milk yield MH (g) MM 2200 1700 1200 0 5 10 15 20 25 30 35 40 45 50 Days in lactation
Maternal vs direct effects for birth weight
Lamb birth weights (kg) G1 Stressed 4.6 4.2 3.7 5.1 5.0 4.6 G1 Normal Two stress paradigms: pregnancy feeding and dam age Std Error ~0.1kg
Lamb birth weights (kg) G1 Stressed 4.6 4.2 3.7 5.1 5.0 4.6 G1 Normal G2 Stressed 5.0 4.8 5.2 5.2 4.9 6.4 5.4 4.7 4.5 4.8 5.0 4.9 5.8 5.1 G2 Normal Two stress paradigms: pregnancy feeding and dam age Std Error ~0.1kg
G1 vs G2 Birthweight 7.00 6.50 G2 Birthweight 6.00 5.50 5.00 4.50 4.00 3.50 3.50 3.70 3.90 4.10 4.30 4.50 4.70 4.90 5.10 5.30 G1 Birthweight regression ~ -0.5kg/kg
Maternal & direct effects Maternal effect – uterine capacity to grow the fetus (placenta?) Direct effect – growth genes of fetus Negative genetic correlation between maternal and direct effects on birth weight -0.56 -0.44 -0.35 -0.13 -0.10 0.01 0.11
Genetic maternal constraint
800kg 200kg 20kg 20kg 50kg 70kg (Walton & Hammond, 1938)
Cheviot x Cheviot Suffolk x Suffolk Cheviot x Suffolk Suffolk x Cheviot
Lamb birth weights Crossbreeding Embryo transfer Group Birth weight Group Birth weight (lamb in dam) (kg) ± 0.2 (lamb in dam) (kg) ± 0.2 (S x S) in S (S x S) in S 5.2 a 5.9 a large control large control (S x C) in C (S x S) in C 4.4 b 5.0 b Restricted Restricted (C x S) in S (C x C) in S 5.1 a 5.5 ab Luxurious Luxurious (C x C) in C (C x C) in C 4.1 b 5.1 b small control small control
Lamb birth weights Crossbreeding Embryo transfer Group Birth weight Group Birth weight (lamb in dam) (kg) ± 0.2 (lamb in dam) (kg) ± 0.2 (S x S) in S (S x S) in S 5.2 a 5.9 a large control large control (S x C) in C (S x S) in C 4.4 b 5.0 b Restricted Restricted (C x S) in S (C x C) in S 5.1 a 5.5 ab Luxurious Luxurious (C x C) in C (C x C) in C 4.1 b 5.1 b small control small control
Fetal morphometry at day19
Fetal morphometry at day19 Group Embryo length (Fetus in Dam) (mm) ± 0.6 (SxS) in S 13.4 c Large control (SxS) in C 11.0 a Restricted (CxC) in S 15.2 d Luxurious (CxC) in C 12.8 bc Small control
Where to now? Refine animal models (type & time of “insult”) of fetal programming Quantify on-farm economic effects Discover the (epigenetic) mechanisms responsible for programming Devise interventions
Thank You
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