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. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist2 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

3. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist3 Strong milk producers have worse fertility? It is all a management challenge

4. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist4 Why should we care? Post partum involuntary culling (even more expensive for first calving cows)

5. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist5 Why should we care?

6. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist6 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

7. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist7 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

8. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist8 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) Fertility culling risk

9. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist9 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 )

10. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist10 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

11. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist11 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)

12. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist12 …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

13. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist13 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

14. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist14 …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

15. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist15 Mechanism of intake regulation according to the hepathic oxidation theory Allen et al 2009

16. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist16 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)

17. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist17 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

18. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist18 Suggested herd goals for NEFA and Ketons

19. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist19

20. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist20 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)

21. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist21 Inflammation Response from 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

22. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist22 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?

23. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist23 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

24. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist24 …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

25. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist25 …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)

26. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist26 …what can we do?  Antioxidant Beta Carotene Its concentration dicreases during transition Recommended dose 600mg/d Can replace Vit A in transition

27. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist27 …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!

28. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist28 …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

29. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist29 …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

30. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist30 Nutritional strategies for Transition cows Late 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

31. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist31 Nutritional strategies for Transition cows Close-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

32. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist32 Nutritional strategies for Transition cows Close-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

33. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist33 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

34. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist34 Drakley’s guidelines for dry cow diets 2006

35. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist35 Drakley’s guidelines for closee-up cow diets 2006 Low K only Full anionic  NEL, Mcal/lb0.66 to 0.68  NEL, Mcal/kg1.45 to 1.50  Metabolizable protein, g/d1100 to 1200  NFC, %30 to 34  Starch, %17 to 20  Dietary Ca, g/d100140  Dietary Ca, %0.901.2  Dietary P, %0.30 to 0.35  Mg, %0.40 to 0.42  Cl, %0.30.8 to 1.2  K, %< 1.3< 1.3  Na, %0.10 to 0.15  S %0.200.3 to 0.4  Added Se, ppm (organic)0.3  Vitamin A (IU/d)100000100000  Vitamin D (IU/d)3000030000  Vitamin E (IU/d)18001800 Prefer use of organic trace elements, including organic Se

36. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist36 Nutritional strategies for Transition cows Fresh 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

37. October 25-26 2011 Dott. Paola Amodeo - SATA Bovine Specialist37 Next problem…. How can we move from theory to practice? Thanks for the attention