Nutrition and reproduction the sheep model

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Nutrition and reproduction the sheep model

• Stewart M. Rhind

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Why are nutrition-reproduction relationships
important

• Wild animals exploiting food resources to the
  full e.g. clutch size in birds - more food
  means more eggs more young reared.
• Domestic animals More offspring more money!

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Why sheep

• Economically important
• Much is known of their physiology
• Reproductive performance is closely related to
  nutrition in some breeds
• Can be used to investigate underlying mechanisms

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A few basic facts

• Ewes typically breed once per year in the autumn
  and produce 1 to 4 lambs
• Ewes (and females of many other species) are
  designed to gain and lose large fat reserves
• The fat reserves have to speak to the ovaries!

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When and how does nutrition determine
reproduction

• Number of eggs produced.
• Number of embryos that survive.
• Reproductive performance can be adjusted at EVERY
  stage
• - during gestation
• - before gestation
• - before the mother is born!

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Reproductive rate is matched to nutritional
resources
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When does nutrition determine lambing rate

• During gestation loss of embryos

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Embryonic loss

• Nutrition effects
• Undernutrition during first month of gestation
  can increase embryo death rate
• Overnutrition during first month of gestation can
  increase embryo death rate

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Embryonic loss

• Other causes of increased loss
• Parity (higher in first)
• Simultaneous lactation
• Heat and cold stress
• High ovulation rate (breed or hormonal
  treatment)

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When does nutrition determine lambing rate

• During gestation loss of embryos
• Days weeks months and years before mating
  ovulation rate

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Short term intake effects and medium term body
condition effects are NOT expressed through the
same physiological mechanisms
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Body condition

• Numbers of large potentially ovulatory ovarian
  follicles at 48h before ovulation
• High body condition (HBC) 4
• Low body condition (LBC) 2

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Intake

• Numbers of large potentially ovulatory ovarian
  follicles at 48h before ovulation
• NOT affected by level of food intake
• ..and so ..

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Hypothetical ewe

• HBC HI 4 LF 4 ovulated
• HBC LI 4 LF 3 ovulated
• LBC HI 2 LF 2 ovulated
• LBC LI 2 LF 1 ovulated

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If there is only one large follicle present it
doesnt matter how good the premating nutrition
is there cannot be more than one ovulation!
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How is the rate of feed intake signalled to the
ovary in the ewe
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Probably by the LH pulse frequency during the 3
days before ovulation high intake more
frequent pulses- low intake less frequent
pulses
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BUT this difference in LH pulse frequency
operates against a background of different
nutrient and hormone signals within the follicle
(leptin )
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When does nutrition determine lambing rate

• During gestation loss of embryos
• Days weeks months and years before mating
  ovulation rate
• Before the ewe is born
• before the ewe is conceived (!)

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Effects of fetal nutrition on adult reproductive
performance.
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Its NOT About

• Contemporary body condition
• - thin animals produce fewer offspring (sheep)
  or breed later (postpartum cattle)
• Pre-mating nutrition
• - higher feed intakes before mating results in
  more offspring

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• It is certain that the significance of correct
  nutrition in child-bearing does not begin in
  pregnancy itself or even in the adult female
  before pregnancy. It looms large as soon as a
  female child is born and indeed in its uterine
  life.
• Edward Mellanby (1933) Lancet ii 1131-1137

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• WHEN
• using this to illustrate the diversity of
  mechanisms through which nutrition can operate
• same fundamental mechanisms may operate to
  control reproduction in the adult animal

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Late Pregnancy / Lactation

• 100 days 100 days Post Proportions
• before birth after birth -weaning
  Single/ Twin
• __________________________________________________
  
• No supplement Supplement Normal 0.43 / 0.54
• Supplement No supplement Normal 0.46 / 0.57
• No supplement No supplement Normal 0.57 /
  0.43
• __________________________________________________
  
• Gunn et al. (1995)

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Mid-pregnancy

• Effects on gonad structure and function
• (Rae et al. (2001 2002)

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Early Pregnancy (0 - 11 days)
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Associated Ontogeny
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HOW
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How

• Nutrient delivery

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Nutrient delivery
Maternal Undernutrition
Maternal Overnutrition
Small Placenta
Normal Placenta
Litter Runt
All affect reproductive development
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How

• Nutrient delivery
• Endocrine signals

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Endocrine signals
Maternal Undernutrition
Maternal Overnutrition
Small Placenta
Normal Placenta
All change with nutritional state All directly
affect gonad function All present and active in
brain
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Other Candidates

• Growth hormone
• Cortisol
• Glucagon
• Prolactin
• Ghrelin
• Progesterone
• Etc.

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What Evidence Is There That

• early life nutrition can alter profiles of these
  hormones
• the hormones can affect reproductive development

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• Gallaher et al. (1998) early fetal
  undernutrition altered profiles of IGF-1
  IGFBP-3 and responses to ACTH later
• Rae et al (2002) undernutrition reduced T3
  concentrations in fetus and ewe.
• Augustin et al. (2003) exposure of bovine
  blastocysts to insulin increased cell number and
  cleavage rate and decreased the number of
  apoptotic bodies

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How

• Nutrient delivery
• Endocrine signals
• Structure and physiology

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Type 2 follicles /mm2 - 110d fetus
Structure and Physiology
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How

• Nutrient delivery
• Endocrine signals
• Structure and physiology
• Reproductive behaviour

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Reproductive Behaviour Effects

• Normal

• Offspring of undernourished ewes

Demasculinisation of some non- reproductive
behaviours By extrapolation - reduced sexual
capacity
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How

• Nutrient delivery
• Endocrine signals
• Structure and physiology
• Reproductive behaviour
• Cellular level effects

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Effects At Cellular Level

• Effects can be expressed on very early embryos

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Effects At Cellular Level

• Effects can be expressed on veryearly embryos
• Modified expression of multiple genes

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Effects At Cellular Level

• Effects can be expressed on veryearly embryos
• Modified expression of multiple genes
• DNA methylation altered by nutrition

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Effects At Cellular Level
Gene
Nutrition
Methylation 1
Methylation 2
F1 Gene expression altered
Gene expression altered
F2 Gene expression unaltered
Gene expression altered
F3 Gene expression unaltered
Gene expression altered
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Transgenerational effects mean that the
reproductive performance of animals is determined
before they are conceived!
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Additional effects

• Reproductive function
• Altered thyroid function

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Additional effects

• Reproductive function
• Altered thyroid function
• Increased cardiovascular disease

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Additional effects

• Reproductive function
• Altered thyroid function
• Increased cardiovascular disease
• Altered neuroendocrine development

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Male offspring more nervous
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Additional effects

• Reproductive function
• Altered thyroid function
• Increased cardiovascular disease
• Altered neuroendocrine development
• Impaired glucose tolerance / diabetes

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Impaired tolerance in late adult life
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Conclusions

• In female sheep nutrition of both the fetus and
  adult can influence reproductive performance
• Many different physiological mechanisms are
  involved
• Effects may be exerted at one time and expressed
  at another