optimising lactation for healthy productivity€¦ · re-bred not re-bred modern cows can lactate...

Optimising Lactation for Healthy Productivity

Chris Knight [email protected] www.foodanimalbiosciences.org

• Optimising Mammogenesis • Obesity, BST

• Optimising Lactogenesis • Angiogenesis, AQP,

• Optimising Milk Yield • rBST

• Optimising Persistency • Extended Lactation

• Optimising Animal Health • bST and cow health

• How are you, cow?

mailto:[email protected]

http://www.foodanimalbiosciecnes.org/

Optimising Mammogenesis

Birth

Puberty

Conception

Pregnancy

Parturition

• LWG prior to puberty is inversely related to eventual milk yield

• This is via an effect on mammary growth

• The effect appears to be permanent

• The effect is mediated through GH, IGF1 and IGF-BP3

The obesity issue

Young lean

Lact d1 lean

Young ob/ob

Lact d1 ob/ob

Problem?

Optimising Mammogenesis

Birth

Puberty

Conception

Pregnancy

Parturition

What about trying to stimulate gestational

mammogenesis?

Is it possible to increase mammary growth using BST?

Stelwagen et al (1992) and (1993)

• Bottom line: No convincing evidence of effect

• Mammogenesis is probably optimal in modern dairy cows

• Observation of postpartum apoptosis supports this

Targets for Optimising Lactation


• Optimising Lactogenesis • Angiogenesis, AQP



• Optimising Milk Quality • Healthy Milks



Lactogenesis: Questions to Consider

Sudden very large increase in blood flow

and nutrient use.

How? Where does glucose come from?

Why does it suddenly go to the mammary gland?

GLUTs and energy partitioning

Chylomicrons Lymph

Chylomicrons Blood

Dietary Fat

Capillary LPL inactivated

Fat cell

NEB: TG > FFA

Glucose low

Lactating animal

Chylomicrons (TG) Lymph

Chylomicrons (TG) Blood

Dietary Fat

Adipose LPL inactivated

NEB: TG > FFA

Low I

Glucose used by MG

Lactating animal

FFA adipose venous blood

FFA MG capillary

MG FFA + G > TG

TG adipose venous blood

Mammary LPL liberates FFA

Note that mammary LPL is high independent of I

Glut 4

Glut 1

Optimising Lactogenesis

Gene Significance Possible role in udder

LALBA P<0.01 Alpha-lactalbumin. Involved in lactose synthesis

and plays a key role in determining milk volume

VEGF P<0.01 Vascular endothelial growth factor. Promotes

angiogenesis

VEGFR1 P<0.001 Receptor for VEGF

VEGFR2 P=0.001 Receptor for VEGF

ANGPT2 P<0.01 Angiopoietin 2, promotes angiogenesis in

conjunction with VEGF

RTK P=0.001 Tyrosine kinase type 2 receptor, receptor for

ANGPT1 and ANGPT2

TGFB1R1 P=0.001 Receptor for TGFB, which is an anti-

proliferative factor for mammary cells

TGFB1R2 P<0.001 Receptor for TGFB

IGFBP5 P<0.001 Binding protein that prevents the cell-survival

activity of IGF1, hence regarded as pro-apoptotic

in mammary tissue

TBXAS1 P=0.001 Thromboxane-A synthase 1, catalyzes the

conversion of prostaglandin to the

vasoconstrictor, thromboxane

• Lactogenesis is not normally problematic in dairy cows, BUT:

• New evidence indicates that ANGIOGENESIS is a late event that we do not yet understand

• Question: could improved angiogensis prevent postpartum apoptosis?

• And….

Table. Developmentally-regulated genes with highest expression in early lactation

5 5

5

5 5

5 5 5

5 5 5

5 5 5

5 5 5

5

5 5

5 5 5

5

5 5

5

5

5

5 5

5 5 5

5 5

5 5 5

5

Non-lactating cow

Lactating cow

15 litre

30 litre

5 litre

125 litre

30 litre

Water Flux

Aquaporins: water channels

AQP1 (CHIP28) expressed in Xenopus laevis oocyte (right) After Agre and Parker, 1991

The "hourglass" AQP structure. Symmetrical repeats of 3 membrane spanning domains fold such that conserved NPA motifs form a neutral central pore

Mammary Aquaporins

• And…

• The switch-on of water transport is not understood

• Developmental regulation supports a role for AQP1 or AQP3, cellular localisation is strongly indicative of AQP5

• Hypothesis: Water flux is mediated by AQP5, which is expressed prepartum but active postpartum

Are there AQP on the mammary Golgi membrane?

If so, are they developmentally regulated?

AQP?

AQP?

AQP?



• Optimising Lactogenesis • Angiogenesis, AQP, Obesity





rBST in the US dairy industry

https://www.elanco.com/products-services/enhancing-health-of-food-animals.aspx

BST stands for bovine somatotrophin

Somatotrophin is US for growth hormone (GH)

GH was first described more than 70 years ago

Effects on lactation were noted in rats, then in cows as long ago as 1937

Pituitary extracts containing GH were extensively researched as lactation enhancers in 1940s

BST: Background and History

BST was produced using recombinant DNA technology in the early 1980s

Several companies competed to produce the first viable product

First rBST study in dairy cows in 1982

By 1992 there were >1000 studies in >40,000 cows

>1,500 publications since 1993

rBST

Bauman et al, 1985 J Dairy Sci. 68, 1352-1362

What it does

+ BST

Repartitions nutrients towards udder

Causes mobilisation initially…

…then increased intake

Homeorhetic

How it does it

Energy Balance

Cows do NOT get thin!

They may even get too fat!

BST approved for use in >25 countries Posilac (Monsanto) gained US approval in Nov

1993 Was sold in US by Protiva starting Feb 1994 Initially made in Austria Since march 2006 produced in Georgia, USA Was licensed to Elanco outwith US Freely available to US farmers without

prescription 2008: Posilac product sold to Elanco

Commercial Product

500mg zinc methionyl BST

Pre-packed syringe

Administered by i.m. injection

Given once every two weeks

Starting after 60d postpartum Standard management for high-yield cow

Do not use within 2wk of slaughter

The Product

Pre-C Post-C Pre-

BST

Post-

BST

Milk

kg/d

27.2 28.8 28.7 33.0

Fat

%

3.67 3.64 3.63 3.57

Prot

%

3.21 3.15 3.19 3.17

SCC 3.22 3.08 3.10 3.17

Commercial Responses

Use of BST in dairy cows is banned

Importation of dairy products produced with BST is allowed

Importation of BST is allowed

Experimental use of BST is allowed under relevant control

Current EU Position

Perceived Safety Issue

The bottom line is that this mom has come to the same conclusion as this Dr. had previously: that milk and dairy products from cows treated with rbST are safe for my children and me to consume.

Why stop?

0 100 200 300 400 500

Days in milk

20

30

40

50

Mil

k y

ield

(k

g/d

)

Re-bred

Not re-bred

Modern cows can lactate for at least 18 months

But this is US data, with BST

BST increases lactation persistency

10 15 20 25 30 35 40

Week of lactation

4

8

12

16

Mil

k y

ield

(k

g/w

k,

sin

gle

gla

nd

)

3X + BST

BST

3X

2X

Optimum rebreeding time

Dogma: 60d

De Vries et al (2006) USA

What about Europe?

Are we missing an opportunity?

60% of vet costs are incurred in the first 45d of lactation

Stage of lactation

Mil

k y

ield

Metabolic problem sat peak lactation

Increased m astitis,lam eness

High yieldat drying-off

Calving Drying-off

Failure to rebreed

Extrem e riskperiod

Risk avoidance

Conventional lactation: 3 risk periods

Extended lactation: 2 risk periods

Milk y

ield

Autumn Autumn Autumn Autumn

Milk y

ield

Autumn Autumn Autumn Autumn

Persistency must be improved

So what is extended lactation?

• Delayed rebreeding

Combined with….

• Management for increased persistency

Strategies for improving persistency

Breed for increased persistency

Identify the persistent cow, delay re-breeding

Manage the whole herd for increased persistency

Managing for increased persistency without BST

Would the combination of frequent milking and more appropriate nutrition increase lactation persistency?

Lactation persistency: 9 months M

ilk y

ield

(kg

/d) Supplemented

Normal

Anovar: n.s.(P=0.07)

15

30

5 35Week

3X

2X

Anovar: P=0.03

Week5 35

Nutrition Milking Frequency

Effect of pregnancy on lactation persistency

-10 -5 0 5 10 15 20 25 30

Week of pregnancy

0

2

4

6

8

10

12

14

Half-u

dd

er

milk y

ield

(kg

/d)

Lactation persistency: 16 months

Milking frequency

5 10 15 20 25 30 35 40 45 50 55 60 65

standardised lactation week

0

5

10

15

20

25

Half-u

dd

er

milk y

ield

(kg

/d)

Thrice daily

Twice daily

A 60 week lactation could become 100 weeks

Milk quality during extended lactation

Rebreeding and health

300

400

500

600

700

Ca

lvin

g i

nte

rva

l (d

)

Control Extended

Target

Target

Actual

Actual

Reproductive problems at 9 months were different to usual 2 month problems

Outcome was similar

All of the cows remained healthy throughout two eighteen month lactations

Extended lactation: Profitability

• For 100 cows: – extra cost of

£22K

– extra revenue of £42K

– extra profit of £20K

One ‘recipe’ for extended lactation (there could be others)

• High yielding cows • Frequent robotic milking • Quality feed, year round • Bring the feed on gradually, but then keep it on • Careful attention to lactation curve • All-year-round partial housing • Re-breed:

– at 9 months – or at time dictated by lactation curve

• Partnership with vet

rBST use: consequences for animal health and consumer safety

BST: a distressing product • CWF analysis by Joyce D’Silva

BST is a cynical abuse of both the dairy cow and the dairy farmer • Prof John Webster, Bristol Univ. Vet. School

https://www.elanco.com/products-services/enhancing-health-of-food-animals.aspx

Metabolic effects of BST

0.2 BCS units loss in entire lactation

The milk yield response is comparable to thrice-daily milking

The milk yield response is sub-maximal

The cow retains control

Incidence of mastitis and lameness

Control BST Control BST

0

10

20

30

Co

ws

aff

ec

ted

(%

)

n.s. n.s.

Heifers Cows

Control BST Control BST

0

10

20

30

n.s. P<0.001

Heifers Cows

Mastitis Lameness

Conclusions on cow health Injection site reactions are unacceptable

BST is associated with a small but measurable increase in disease incidence

Cause and effect has not been established

Irrespective of the degree and mechanism, this is unacceptable...

...as is continuous genetic improvement with no regard to better practice







• Health and Welfare Technology

Sensors for Dairy health and Welfare: The Dairy ICT Project

• In the Dairy ICT project we are developing new uses for accelerometer collars, expanding the utility of milk metabolomics and building novel biomarker technologies

• Outputs from these novel technologies will be integrated into ICT-based "smart" husbandry support systems for use by dairy farmers.

Dairy ICT Project will expand existing proven technologies

Herd Navigator: Progesterone

LDH BHB

Oestrus detection

Add SAR

A

Add lameness

Add feeding activity

Dairy ICT Project will view biomarkers differently

Dairy ICT Project will develop minimalist approaches to smart systems

Know desired state

Integrate, compare, evaluate,

Know previous

state

Know current state

Welfare biomarker

data

Accelerometer collar

data

Milk metabolomic

data

Initiate Action

Existing state of art

data

Existing state of art

data

Dairy ICT Project, Example biomarker data

Dairy ICT Project, example biomarker data

Dairy ICT Project, example activity data

Dairy ICT Project, www.dairyict.eu

Thank you!

You may also be interested in the new COST Action FA1308,

DairyCare www.dairycareaction.org

optimising lactation for healthy productivity€¦ · re-bred not re-bred modern cows can lactate...

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