In this talk Energy metabolism and fertility: focusing on what - - PDF document

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In this talk Energy metabolism and fertility: focusing on what - - PDF document

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1/18/2017 Metabolic Health and antioxidants in dairy cows The sole way to reproductive performance? Jo Leroy DVM, PhD Jo.leroy@uantwerpen.be In this talk Energy metabolism and fertility: focusing on what really matters Fertility

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Metabolic Health and antioxidants in dairy cows

The sole way to reproductive performance?

Jo Leroy

DVM, PhD Jo.leroy@uantwerpen.be

In this talk …

  • Energy metabolism and fertility: focusing on what

really matters

  • Fertility … the deep dive
  • How sensitive is that oocyte and how

important are anti-oxidants?

  • Conclusions
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Reproduction is …

“The most sensitive cornerstone of modern dairying”

sensitive cornerstone

Metabolic pressure Disease Suboptimal management Social stress Inadequate housing NUTRITION Milk yield Replacement heifers Cost efficiency Longevity Sustainability Environmental pressure FARMER’S INCOME

Lopez-Gatius et al., 2006

Is the cow adapted to the management and is the management adapted to the cow?

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Foto a^persç

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Dairy cows account on body reserves to guarantee milk production! Loss of body condition is correlated with health problems and reproductive outcome

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BCS change is negatively correlated with the cow’s ability to ADAPT (by doing what?). BCS change is positively correlated with the cow’s vulnerability to malfunction and disease.

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The fairy tale of mother nature: ….

… leading to nutrient prioritization … exploited by wise man … ending in suffering cows!

Nutrient prioritization

GLUCOSE

No glucose  no lactose  no milk

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0.5  4.0 mmol/l 3.2  1.5 mmol/l 0.15  1.0 mmol/l

Alternative energy source in peripheral tissue (Glut 4) SA VE ON GLUCOSE

NEB

GLUCOSE

LACTOSE

insulin

LIPOLYSIS

NEFA

Nutrient prioritization

Milk

gluconeogenesis

Ketone bodies

BHB

LIPIDS

  • xaloacetate

VLDL

Gravid uterus

HSL

Glut 1&3 Glut 4

Successfull reproduction?

  • bservation

Dry period Energy balance Genetic merit DMI data management stress Heifer rearing housing disease hygiene transition calving environment Strategy and priorities Farm type Reproductive physiology ration

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Santos et al., 2010

Estrus cyclicity Pregn at first AI

Maternal health and dairy cow fertility: more than only nutrition!

Santos et al., 2010

Vruchtbaarheid: veel meer dan alleen voeding!

Pregn loss in first 60d

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Message at the glance …

1.Any pressure on metabolism gives reduced fertility outcome. 2.Fertility is the best sensor for general well being

  • f the cow (physically and mentally).

3.Milk production is not well related with metabolic stress and thus with reproductive outcome: much more factors are involved. 1.BCS changes are a good indicator.

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In this talk …

  • Energy metabolism and fertility: focusing on what

really matters

  • Fertility … the deep dive
  • How sensitive is that oocyte and how

important are anti-oxidants?

  • Conclusions

What are the symptomes of suffering fertility?

How important is the aspect of oocyte quality in the process of “becoming pregnant”? “First think about the healthy mother … then focus on her eggs!”

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What are the CCP? Chronologically?

  • 1. Puberty and heifer rearing
  • 2. Calving conditions
  • 3. Uterine recovery
  • 4. Onset of ovarian activity
  • 5. Oestrus and ovulation
  • 6. Insemination and conception
  • 7. Supporting early pregnancy

Bovine reproduction in HACCP terms Reproduction: the underground of pathways…

Estrus cyclicity Pregnancy at first service Staying pregnant

Endocrine communication Healthy follicle Timed ovulation Energy balance Nutrition Stress (heat, social, pain, …) Infectious disease Oocyte quality Embryo quality Corpus luteum quality Early uterine environment Carry over effects of energy balance Nutrition Stress (heat, social, pain, …) Infectious disease Uterine environment Corpus luteum quality (epi)Genetic errors Infectious disease

Onset of ovarian activity and ovulation before day 25 post partum Being pregnant with < 2 AI’s at 100 days post partum Preg loss < 5% until day 60 of pregnancy

Confounders: management factors and genetic merit for milk production

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Altered follicular growth and endocrine disturbances reduce oocyte quality

Ovarian activity:

  • Intricate interplay of numerous factors
  • Final goal: timely ovulation of a perfect oocyte

from a healthy follicle

  • Problems:
  • 1. Anovulation
  • 2. Silent oestrus, irrigual oestrus intervals
  • 3. CL persistens
  • 4. Bad follicle quality

Oestrus and ovulation:

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GnRH FSH Hypothalamus Pituitary LH surge LH pulses Pre-ovulatory follicle Selection & Deviation Follicle growth wave Preovulatory

  • estradiol-surge +

Oestradiol + Ovulation

Vanholder et al., 2006 1st AI

Conception

40 wks pregnancy

2nd AI

Ovarian Dysfunctions

Vanholder et al., 2006

Oocyte / embryo / CL

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Oocyte quality:

Conception 90% Early embryo mortality 40% Late embryo mortality 20% Foetal loss 5% Perinatal calf mortality 8%

Importance of oocyte, embryo and corpus luteum quality

  • Dom. follicle
  • viduct

uterus

  • estrogen

Day 0 In heat 12-24 h

  • vulation

AI

Day 6 Embryo in uterus Day 280 Calving

Progesterone

IFN-τ

CL

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  • vulation

OVARY OVIDUCT UTERUS NEB

Metabolic Δ Endocrine Δ

Elongated conceptus Expanded blastocyst Compact morula Liver

NUTRITION

Energy and Protein

Metabolic Δ Endocrine Δ

60 – 90 days

Carry over effects on

  • ocyte

and follicle quality Carry

  • ver

effects

  • n CL

function High progesterone metabolism in the liver

PROGESTERONE IFN-τ

PGF2α

FF

Affecting steroid production, FF and

  • ocyte quality

Affecting health

  • f primordial

follicle Affecting embryo quality, micro- environment and endometrium secretions

AFFECTED

  • Oocyte quality
  • Steroid secretion

CONCEPTION FAILURE LOW PROGESTERON EARLY EMBRYO MORTALITY

  • 90-60 d

0 d

1 d 2 d 4 d 8 d 6 d 17 d

  • 2 d

Primary follicle Dominant follicle Mature oocyte 2 cell embryo 32 cell embryo Corpus luteum

  • vulation

OVARY OVIDUCT UTERUS NEB

Metabolic Δ Endocrine Δ

Elongated conceptus Expanded blastocyst Compact morula Liver

NUTRITION

Energy and Protein

Metabolic Δ Endocrine Δ

60 – 90 days

Carry over effects on

  • ocyte

and follicle quality Carry

  • ver

effects

  • n CL

function High progesterone metabolism in the liver

PROGESTERONE IFN-τ

PGF2α

FF

Affecting steroid production, FF and

  • ocyte quality

Affecting health

  • f primordial

follicle Affecting embryo quality, micro- environment and endometrium secretions

AFFECTED

  • Oocyte quality
  • Steroid secretion

CONCEPTION FAILURE LOW PROGESTERON EARLY EMBRYO MORTALITY

  • 90-60 d

0 d

1 d 2 d 4 d 8 d 6 d 17 d

  • 2 d

Primary follicle Dominant follicle Mature oocyte 2 cell embryo 32 cell embryo Corpus luteum

  • vulation

OVARY OVIDUCT UTERUS OVARY OVIDUCT UTERUS NEB

Metabolic Δ Endocrine Δ

NEB

Metabolic Δ Endocrine Δ

Elongated conceptus Expanded blastocyst Compact morula Elongated conceptus Expanded blastocyst Compact morula Liver

NUTRITION

Energy and Protein

Metabolic Δ Endocrine Δ

NUTRITION

Energy and Protein

Metabolic Δ Endocrine Δ

60 – 90 days

Carry over effects on

  • ocyte

and follicle quality Carry

  • ver

effects

  • n CL

function High progesterone metabolism in the liver

PROGESTERONE IFN-τ

PGF2α PGF2α

FF

Affecting steroid production, FF and

  • ocyte quality

Affecting health

  • f primordial

follicle Affecting embryo quality, micro- environment and endometrium secretions

AFFECTED

  • Oocyte quality
  • Steroid secretion

CONCEPTION FAILURE LOW PROGESTERON EARLY EMBRYO MORTALITY

  • 90-60 d

0 d

1 d 2 d 4 d 8 d 6 d 17 d

  • 2 d
  • 90-60 d

0 d

1 d 2 d 4 d 8 d 6 d 17 d

  • 2 d
  • 90-60 d

0 d

1 d 2 d 4 d 8 d 6 d 17 d

  • 2 d

Primary follicle Dominant follicle Mature oocyte 2 cell embryo 32 cell embryo Mature oocyte 2 cell embryo 32 cell embryo Mature oocyte 2 cell embryo 32 cell embryo Mature oocyte 2 cell embryo 32 cell embryo Mature oocyte 2 cell embryo 32 cell embryo Corpus luteum

* High Genetic Merit

Heat Stress Infectious Disease Leroy et al., Reproduction in Domestic Animals, 2008

Carvalho et al., JDS 2014

Britt’s Hypothesis

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Message at the glance …

  • Identify the CCP in the process of

reproduction

  • Cows will only reproduce when they are

metabolically healthy

  • Reproduction is a finely tuned interplay

between many factors, ultimately resulting in a healthy oocyte that should be fertilised and lead to pregnancy at term.

In this talk …

  • Energy metabolism and fertility: focusing on what

really matters

  • Fertility … the deep dive
  • How sensitive is that oocyte and how

important are anti-oxidants?

  • Conclusions
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Oocyte quality is reduced in lactating dairy cows.

  • Altered follicular environment
  • Sensitive to metabolic stress
  • Sensitive to feed composition
  • Not all studies are univocal: Matoba et al. JDS

2012

  • Simulated NEB conditions in vitro significantly

reduce oocyte quality

  • Oocytes suffer from more oxidative stress

The black box

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The story of the “fatty acid black-box”!

Fat feeding and … effects on:

Appetite, DMI Fermentation, digestion and absorption Energy balance Immune function Glucose tolerance and insulin sensitivity Milk production Endocrine signaling

Fertility?

Recent IN VIVO studies:

 Zeron et al., 2002: positive effects of fish oil supplemented diets on oocyte quality and chilling  Adamiak et al., 2006: altered lipid intake is reflected in changed fatty acid composition in follicular fluid and cumulus oocyte complex  Bilby et al, 2006: negative effects of n-6 rich diets on oocyte quality  Fouladi-Nashta et al. 2007: positive effect of 800g Megalac for 14d on oocyte quality  Thangavelu et al., 2007: reduced embryo quality after OPU of cows supplemented with SAT compared to LNA or LA supplemented cows  Petit et al., 2008: negative effect of LNA on embryo quality at ET.  Fouladi-Nashta et al., 2009: Holstein cows fed palmitic and oleic, linoleic or lenolenic acids had altered plasma fatty acid profile, but no effect on embryo development  Cerri et al., 2009: positive effect of LA on embryo quality at ET  Zachut et al., 2010: positive effect of flaxseed oil on oocyte quality in dairy cows  Jungheim et al., 2011: elevated FF NEFA correlated with poor COC morphology  Ponter et al., 2012: diet high in LNA increase Prostoglandin E2 synthase-1 in COCs  Guardieiro et al., 2013: negative effect of LA on embryo cryotolerance in Nelore heifers

Fat affects oocyte and embryo?

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The importance of timing

Stressors Oxidative stress

NEB INFECTION STRESS PAIN HEAT Sensivity / susceptibility Antioxidants CELL DAMAGE DISEASE ↓ IMMUNITY ↓ FERTILITY

Oxidative stress and fertiity

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Oxidative stress and fertiity

  • Direct OS effects on follicle and oocyte
  • Indirect OS effects on follicle and oocyte
  • Protecting oocyte by:
  • 1. Avoid too high OS levels
  • 2. Protect oocyte by increasing anti-oxidative

capacities

  • 3. Problems: AO status of the cow? Bio-availability?

Type and way of action of the AO used? Many confounders!

NEB  NEFA

Follicle Oocyte Blastocyst

 NEFA

Can we improve the oocyte’s micro- environment?

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ANTI-OXIDANTS AO AO

?

Does beta carotene availability changes with differences in energy balance? Does beta carotene reaches the follicular environment when supplemented?

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Experimental design:

AO in follicular milieu

Blood Follicular fluid aspiration (OPU)

AO in follicular milieu

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R=0,645 (P=0,001) 1=PEB-bC 2=PEB+bC 3=NEB+bC 4=NEB-bC

x10

AO in folliculair milieu

β-caroteen

Screening AO status on the average Flemish dairy farm

>3,5µg/ml bC = optimal 1,5 – 3,5µg/ml bC = sufficient <1,5µg/ml bC = deficient

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Oxidative stress

Questions …

  • Actual needs for anti-oxidants?
  • Actual oxidative status in dairying?
  • Current advices are marketing driven …
  • Importance of farm type?
  • Differences between animals on same farm?
  • Effects of phase in lactation (energy balance)?

Screening AO status

  • V. Shortages?

B-carotene

>3,5µg/ml bC = optimal 1,5 – 3,5µg/ml bC = marginal <1,5µg/ml bC = deficient

Vitamine E

>3µg/ml vit E = sufficient <3µg/ml vit E = deficient 23% 57% 20% 33% 67%

Dry: 21% Early Lact: 72% Moment AI: 7% Dry: 31% Early lact: 58% Moment AI: 10%

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Other findings

  • iCheck as ‘cow side’ test for estimation of AO status
  • Due to rather big inter-animal variation on one farm 

sampling of 4 cows per laction group is advisable

  • Early lactation (metabolic stress and NEB)  - effect on AO

status

  • Fresh grass (grazing)  + effect on AO status (only for bC!)

 Biggest effect seen during dry period! (bC, Vit E & GPx)

  • Summer season  - effect on AO status
  • bC and Vit E concentrations are strongly correlated
  • GPx is not correlated to bC and Vit E concentrations in the blood
  • The farmer’s decision to “supplement” is not visible in the blood composition
  • Icheck works perfect as cow side test to assess bC concentrations

Message at the glance …

  • Oocyte suffers from maternal metabolic stress
  • Dietary intervention may affect oocyte quality
  • NEVER expect an easy INPUT  desired OUTPUT

link when it comes to fertility! Beware of the blackbox paradigm

– Many interactions – Many confounding factors – Many indirect effects

  • Optimizing anti-oxidant conditions may be

promising

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In this talk …

  • Energy metabolism and fertility: focusing on what

really matters

  • Fertility … the deep dive
  • How sensitive is that oocyte and how

important are anti-oxidants?

  • Conclusions

Conclusions

  • Modern dairy cows need our support
  • Never shoot a golden bullet into a black box!
  • Oocyte quality should be considered as an “end

product” that tells you how healthy the cow is AND has been .

  • Oocyte quality becomes relevant towards the end
  • f the “pathway to fertility”.
  • Feeding for improved oocyte quality is possible

but not always straight forward.

  • Always put the metabolic health first!
  • Antioxidants deserve much more scientific

attention.

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Cartoon thanks to James Husband