Summarizing the metabolic diseases as a main influence on reproductive failure

1. Summarizing the metabolic diseases as a main influence on reproductive failure Paola Amodeo Regional Breeders Association of Lombardy Crema– Italy S.A.T.A. Bovine Nutrition Specialist amodeo.p@apa.mi.it

2. Can genetical selection of dams & sires stop the fertility downbound trend? • It can help but it is surely not the main drive • Management and nutrition have still a lot to do and say about it Dott. Paola Amodeo - SATA Bovine Specialist

3. Strong milk producers have worse fertility?It is all a management challenge Dott. Paola Amodeo - SATA Bovine Specialist

4. Why should we care? Post partum involuntary culling(even more expensive for first calving cows) Dott. Paola Amodeo - SATA Bovine Specialist

5. Why should we care? Dott. Paola Amodeo - SATA Bovine Specialist

6. Transition cow metabolic diseases lead to reproductive failure • We must search for the causes of such diseases and losses • Cow comfort (housing, space, grouping) • Environmental (heat stress) • Nutritional : mainly related to NEB in the transition period • Seems to be a very important area Dott. Paola Amodeo - SATA Bovine Specialist

7. Dairy Cow Transition • We are not dealing with macroscopic and gross nutrition mistakes on animal requirements or on macro and micro mineral umpairing as it used to be • Now the problem is more subtle and maybe more sneaky • At the moment it is the main area on which all researchers and nutritionists are concentrating their efforts Dott. Paola Amodeo - SATA Bovine Specialist

8. Strong physiological changes from dry cow (pregnancy) to lactation Suppression of appetite Immune system Suppression Higher risk for fatty liver, DA, RP, Ketosis and milk fever + masitis and metritis (infectuous) culling risk Fertility Dott. Paola Amodeo - SATA Bovine Specialist

9. Main Goal: Control fat mobilization through the transition period to decrease DMI depression and immune suppression from high non esterified fatty acids (NEFA) Latest theory of feed intake control to formulate diets for transition cows (M.S.Allen and B.J. Bradford – Michigan State University) Dott. Paola Amodeo - SATA Bovine Specialist

10. Hepatic Oxidation Theory (HOT)Food intake is controlled by fuels oxidation in the liver through a system of connections to the hepatic vagus nerve • Firing rate of the nerve determined by liver oxidation of fuels wich produces ATP: • Higher firing rate= hunger • Lower firing rate= satiety • Higher ATP= more oxidation=lower firing rate=satiety We still do not know how ATP concentration influences firing rate of hepatic vagus nerve Dott. Paola Amodeo - SATA Bovine Specialist

11. Fuels for oxidation in ruminants are: • Fatty acids (from diet and/or body reserves) • Propionate (by microbial fermentation) • Lactate (by muscles and gut tissues from glucose) • Amino acids (from protein degradation) Dott. Paola Amodeo - SATA Bovine Specialist

12. …Fatty acids… • NEFA from body fat mobilization (readily oxidized) suppress DMI in the transition period • Fat mobilization is affected by plasma insulin concentration • High insulin = fat synthetis • Low insulin = fat mobilization Dott. Paola Amodeo - SATA Bovine Specialist

13. But plasma Insulin decreases by 50% in the pre calving weeks • Lower insulin=more fat mobilization= higer NEFA • Moreover we have a decreased tissue sensitivity to insulin (insulin resistance ) • Lower glucose utilization (which remains constant despite declining of feed intake) so use of NEFA by muscles increases Dott. Paola Amodeo - SATA Bovine Specialist

14. …At calving.. • Plasma glucose concentration drops dramatically at calving • Plasma insulin and insulin tissue sensitivity remain low • Plasma NEFA concentration remain high for several weeks Ketones in plasma • DMI decreases • Risk of fatty liver • no new glucose production • No insuling produced in the pancreas Dott. Paola Amodeo - SATA Bovine Specialist

15. Mechanism of intake regulation according to the hepathic oxidation theoryAllen et al 2009 Dott. Paola Amodeo - SATA Bovine Specialist

16. NEFA and transition diseases risk • High NEFA in the 2 weeks before calving is associated with • 2 to 4 times increased risk of LDA (Cameron et al, 1998; LeBlanc et al, 2005; Opsina et al, 2010) • 1.8 times increased risk of retained placenta (RP) (LeBlanc et al 2004) • 2 times increased of culling before 60 days in milk (DIM) and 1.5 times increased risk of culling over the whole lactation (Duffield et al, 2005) • Reduced milk yield (Carson, 2008; Opsina et al, 2010) Dott. Paola Amodeo - SATA Bovine Specialist

17. BHBA and Transition diseases • Subclinical ketosis (BHBA > 1200 – 1400 mol/L) in early lactation is associated with • 3 to 8 times increased risk of LDA (Duffield, 1997; Geishauser et al, 2000b; LeBlanc et al 2005) • Decreased probability of pregnancy at first AI (Walsh et al, 2008) • Decreased milk production (Duffield, 2009) • Increased duration and severity of mastitis (Suriyasathaporn, 2000 Dott. Paola Amodeo - SATA Bovine Specialist

18. Suggested herd goals for NEFA and Ketons Dott. Paola Amodeo - SATA Bovine Specialist

19. Dott. Paola Amodeo - SATA Bovine Specialist

20. AVOID NEB! (Negative Energy Balance) • It suppresses immune function • It promotes metabolic disorders • It potentially explaines the relationship between infectious and non infectuous transition disorders • Important role of inflammation response in infectuous diseases as well as metabolic disorders (B.Bradford-Kansas State University) Dott. Paola Amodeo - SATA Bovine Specialist

21. Inflammation Responsefrom infectuous disorders • Activated immune cells release of nitric oxide, prostaglandins and citokines • Citokines stimulate systemic inflammatory responses (>Temp,<DMI) • Citokines activate production of acute phase proteins (haptoglobin and serum Amyloid A by the liver • Mammary and uterin infections • Local and systemic inflammation • Coliform Mastitis • Endotoxines, cytokines and acute phase proteins • Metritis • High plasma haptoglobin prior to clinical signs of metritis These non specific inflammatory responses promote development of metabolic disorders by decrease in DMI and unpair metabolic functions Dott. Paola Amodeo - SATA Bovine Specialist

22. Inflammation-based pathogenesis of transition cows disorders • Wide evidence of link between inflammation and transition disorders, unpaired repro efficiency, lower plasma calcium concentrations • Metabolic Disorders derive also from inflammation caused by • Infections (se above) • Oxidative stress (lipids meet ROS (reactive oxigen species) and produce lipid peroxides • Endotoxins from the gut (sub acute ruminal acidosis? Dott. Paola Amodeo - SATA Bovine Specialist

23. Consequences of such inflammation • Disruption of normal metabolism • Induction of metabolic diseases • Suppression of immune function by oxidative stress which damages lipids, proteins and DNA of immune cells Dott. Paola Amodeo - SATA Bovine Specialist

24. …in summary…. • A combination of insults including infection, chronic inflammation in obese cows an lipid peroxide formation promotes systemic inflammation during transition • Inflammation impairs immune function making cows more susceptible to infectuous disorders and to metabolic disorders Dott. Paola Amodeo - SATA Bovine Specialist

25. …what can we do? • Antioxidants: Vit E and Selenium • Contribute to ROS neutralization (both) • Decrease production of inflammatory cytokines (only Vit E) • Effects on immune function (only Vit E) • Raccomended doses • VIT E = 1500 UI/d in close-up cows • Organic Selenium (if deficient) 0,3 ppm/d (FDA limit) Dott. Paola Amodeo - SATA Bovine Specialist

26. …what can we do? • Antioxidant Beta Carotene • Its concentration dicreases during transition • Recommended dose 600mg/d • Can replace Vit A in transition Dott. Paola Amodeo - SATA Bovine Specialist

27. …what can we do? • Metabolic modifiers: PPAR • Agonists of peroxisome receptors • Decrease Plasma NEFA concentration • Promote fatty acid oxidation in liver • Limit triglyceride accumulation and production of lipid peroxides NOT APPROVED! Dott. Paola Amodeo - SATA Bovine Specialist

28. …what can we do? • Choline • Limits peroxides formation by decreasing plasma NEFA and clearing triglycerides from the liver • In the rumen protected form it may contribute to immune functions Dott. Paola Amodeo - SATA Bovine Specialist

29. …what can we do? • Anti inflammatory agents: NSAIDs (non-steroid anti-inflammatory drugs) • Prevention of hypoglicemia • Effective at reducing body temperature • Do not consistently improve recovery from infections • Better activity against metabolic disorders • Aspirin: lower production of haptoglobine Future research needed Dott. Paola Amodeo - SATA Bovine Specialist

30. Nutritional strategies for Transition cowsLate lactation and far off Dry Cows • Limit mobilization of body fat by controlling BCS during late lactation • Feed high NDF, low energy in dry cows • Feed low concentration of high fermentable starch in dry cows Dott. Paola Amodeo - SATA Bovine Specialist

31. Nutritional strategies for Transition cowsClose-up • Feed high fill, moderate energy diets in close-up cows (Drackley, Overton) • control energy intake • reduce fat depots • sustain plasma glucose through calving • increase amount of ruminal digesta which dicreases risk of DAs • increase bufferuing capacity (acidosis) • increase acetate production, dicreases propionate production Dott. Paola Amodeo - SATA Bovine Specialist

32. Nutritional strategies for Transition cowsClose-up • Correct choice of forages • Low potassium content if grasses • Not too high NDF fermentability • Wheat straw has a slow rumen passage and slows down diet passage rate (mat) also increasing digesta retention • FATs: should not be fed • Can depress feed intake and increase fat oxidation Exception: Ω3???? Perhaps antiinflammatory Dott. Paola Amodeo - SATA Bovine Specialist

33. Overall goals for energy intake of both far-off and close-up cows • Far off cows (dry off until ~ 3 weeks precalving • ~18 Mcal of NEL per day • Close-up cows (last 3 weeks before calving) • ~19 Mcal of NEL per day • Vary energy density of diets based upon group DMI • If energy intake low, increasing energy density may help • If energy intake too high, bulk up the diet to control energy intake • The ONLY way to minimize management/facility-induced variation in feed intake among cows is to ensure that the group is FULLY FED Dott. Paola Amodeo - SATA Bovine Specialist

34. Drakley’s guidelines for dry cow diets2006 Dott. Paola Amodeo - SATA Bovine Specialist

35. Drakley’s guidelines for closee-up cow diets2006 Low K onlyFull anionic • NEL, Mcal/lb 0.66 to 0.68 • NEL, Mcal/kg 1.45 to 1.50 • Metabolizable protein, g/d 1100 to 1200 • NFC, % 30 to 34 • Starch, % 17 to 20 • Dietary Ca, g/d 100 140 • Dietary Ca, % 0.90 1.2 • Dietary P, % 0.30 to 0.35 • Mg, % 0.40 to 0.42 • Cl, % 0.3 0.8 to 1.2 • K, % < 1.3 < 1.3 • Na, % 0.10 to 0.15 • S % 0.20 0.3 to 0.4 • Added Se, ppm (organic) 0.3 • Vitamin A (IU/d) 100000 100000 • Vitamin D (IU/d) 30000 30000 • Vitamin E (IU/d) 1800 1800 Prefer use of organic trace elements, including organic Se Dott. Paola Amodeo - SATA Bovine Specialist

36. Nutritional strategies for Transition cowsFresh cows (0-14 days post partum) • Avoid highly fermentable starch sources (high propionate production stimulation of oxidation of Acetyl CoA suppress feed intake) • Dry Corn is best (provide glucose precursors and less propionate) • As gut fills begins to dominate feed a less filling and more fermentable diet Dott. Paola Amodeo - SATA Bovine Specialist

37. Next problem…. How can we move from theory to practice? Thanks for the attention Dott. Paola Amodeo - SATA Bovine Specialist