Role of nutrition and metabolism on fertility in dairy cows Matt Lucy F21C Animal Reproductive Biology Division of Animal Sciences University of Missouri, Columbia, USA

Lactose (milk sugar) A disaccharide composed of galactose and glucose

Lactose (milk sugar) Two molecules of glucose are used in the production of one molecule of lactose

Ever-Green-View My 1326-ET Waldo, Wisconsin USA February 2010 32,805 kg of milk* 1,267 kg fat 974 kg protein 365 d lactation *3-times average US cow in 2010

How much glucose per day? 72 g of glucose to produce 1 kg milk 100 kg milk per day 7.2 kg glucose per day

Glucose synthesis Healthy later lactation or dry cow Drackley (1999) J. Dairy Sci. 82:2259-2273.

Glucose supply and demand: Prepartum and early lactation Overton (2001) Proceedings of the Western Canadian Dairy Seminar

Glucose synthesis Cow in negative energy balance Drackley (1999) J. Dairy Sci. 82:2259-2273.

Bovine embryonic and fetal development depends on glucose Photo courtesy of The Drost Project (University of Florida)

The Warburg Effect Metabolic Requirements for Cell Growth Vander Heiden et al. (2009) Science 324:1029-1033

Plasma GH concentrations in postpartum dairy cows Kobayashi et al. (1999) Endocrinology 140:3947-3954.

GH, GHR, IGF1, and insulin in Postpartum Cows Hypothalamus Pituitary GH GHR Liver Insulin Nutrient Partitioning Milk Production Stimulatory action Inhibitory action

Journal of General Physiology (1931)

GH/Insulin Antagonism IGF-I Hypothalamus Pituitary GH GHR GHR Liver Adipose Insulin IR IR Pancreas Glucose Glucose Mammary NEFA Stimulatory action Inhibitory action Lucy 2004 (NZSAP Proceedings)

75th Annual Hoard’s Dairyman Cow Judging Contest

GH/Insulin antagonism during lactation IGF-I Glucose supply Glucose supply

Dexcel Strain Trial Hamilton, New Zealand 2001-2003 Three strains NA90 NZ90 NZ70 Two different feeding levels Low High

Milk energy production and body condition score 2003 Strain Trial Cows Lucy et al. (2009) J. Dairy Sci. 92:526-539.

Dexcel Strain Trial Hamilton, New Zealand 2001-2003 Lucy et al. (2009) J. Dairy Sci. 92:526-539.

Theoretical model of milk production, energy balance, and body condition score Lucy (2009) Proceedings of the 44th Annual Pacific Northwest Animal Nutrition Conference

GH Uterus Ovary Insulin Adipose Glucose NEFA Liver IGF1

Embryonic loss for heifers and cows Santos et al. (2004)

Methods Pregnant Holstein dairy heifers (n = 43) were randomly assigned to one of two groups. After calving: One group was dried off immediately (not milked; nonlactating). The other group was milked normally (twice daily; lactating). Slaughter at 28, 35, or 42 d of pregnancy. Green et al. (2012) Reproduction (in press) Lucy et al. (2012) J. Dairy Sci. (submitted)

Postpartum Glucose Trt P < 0.001 Status P < 0.090 Trt*Status NS DPP P < 0.070 Trt*DPP NS Status*DPP P < 0.007 T*S*DPP NS Green et al. (2012) Reproduction (in press)

Postpartum insulin Trt P < 0.001 Status NS Trt*Status NS DPP NS Trt*DPP NS Status*DPP NS T*S*DPP NS Green et al. (2012) Reproduction (in press)

Postpartum IGF1 Trt P < 0.001 Status P < 0.019 Trt*Status NS DPP P < 0.001 Trt*DPP P < 0.001 Status*DPP NS T*S*DPP NS Green et al. (2012) Reproduction (in press)

Postpartum NEFA Trt P < 0.001 Status NS Trt*Status NS DPP P < 0.001 Trt*DPP P < 0.001 Status*DPP NS T*S*DPP NS Green et al. (2012) Reproduction (in press)

Day 28 bovine fetuses 7 mm Cow 15 Cow 34 Cow 39 Green et al. (2012) Reproduction (in press)

Effect of lactation on fetal wt (g) Nonlact Day 28 fetus 0.11 + 0.15 0.12 + 0.11 Day 35 fetus 0.61 + 0.11 0.80 + 0.15 Day 42 fetus 1.64 + 0.10 2.02 + 0.11 Treatment P < 0.06 Day P < 0.001 Status P < 0.005 Green et al. (2012) Reproduction (in press)

Effect of lactation on placental wt (g) Nonlact Day 28 placenta 1.1 + 2.2 1.2 + 1.6 Day 35 placenta 8.1 + 1.7 13.2 + 2.2 Day 42 placenta 16.8 + 1.5 25.0 + 1.6 Treatment P < 0.01 Day P < 0.001 Green et al. (2012) Reproduction (in press)

Fetal tissues and cavities Drawing from: University of Guelph Department of Animal and Poultry Science

Maternal and fetal glucose Maternal plasma Fetal fluids Treatment P < 0.001 Slaughter NS T*S NS Treatment P < 0.002 Slaughter P < 0.001 T*S NS Lucy et al. (2012) J. Dairy Sci. (submitted)

Effect of status on fetal wt (g) Pregnant to 1st AI Pregnant to 2nd or 3rd AI Day 28 fetus 0.14 + 0.10 0.08 + 0.13 Day 35 fetus 0.91 + 0.08 0.49 + 0.16 Day 42 fetus 2.05 + 0.10 1.61 + 0.11 Day P < 0.001 Status P < 0.005 Green et al. (2012) Reproduction (in press)

Day 35 bovine fetuses Lactating; Pregnant at 2nd AI Not lactating; Cow 15 Cow 34 Cow 39 Lactating; Pregnant at 2nd AI Not lactating; Pregnant at 1st AI Green et al. (2012) Reproduction (in press)

Waldron study cows Postpartum uterine weight Lucy and Waldron (unpublished)

Day 3

Day 25

Day 25

Luminal Epithelium of the bovine uterus at 25 dpp Lucy and Waldron (unpublished)

Glucose infusion 0.695 g/min (1 kg/d) Lucy (unpublished)

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Ovary NEFA Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Cytokines Ovary Inflammation NEFA Inflammation Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Cytokines Unhealthy liver Ovary Inflammation NEFA Inflammation Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Cytokines Ovary Inflammation NEFA Inflammation Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Cytokines Ovary Inflammation NEFA Inflammation Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Cytokines Ovary Inflammation NEFA Inflammation Immune cells Adipose AA Glucose Muscle Insulin Mammary Gland

Hypothalamus and Pituitary “Life on the Knife” IGF1 Hypothalamus and Pituitary Liver Growth hormone Uterus Ovary Immune cells Adipose Glucose Muscle Insulin Mammary Gland

Solutions: GH Uterus Ovary Insulin Adipose Glucose NEFA Liver IGF1