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Nutrition and reproduction – the sheep model. Stewart M. Rhind. 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.

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why are nutrition reproduction relationships important
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!
why sheep
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
a few basic facts
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!
when and how does nutrition determine reproduction
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!

when does nutrition determine lambing rate
When does nutrition determine lambing rate?
  • During gestation – loss of embryos
embryonic loss
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
embryonic loss9
Embryonic loss

Other causes of increased loss:

  • Parity (higher in first)
  • Simultaneous lactation
  • Heat and cold stress
  • High ovulation rate (breed or hormonal treatment)
when does nutrition determine lambing rate10
When does nutrition determine lambing rate?
  • During gestation – loss of embryos
  • Days, weeks, months and years before mating – ovulation rate
slide15
Short term intake effects and medium term body condition effects are NOT expressed through the same physiological mechanisms
body condition
Body condition

Numbers of large, potentially ovulatory, ovarian follicles at 48h before ovulation :

High body condition (HBC) 4

Low body condition (LBC) 2

intake
Numbers of large, potentially ovulatory, ovarian follicles at 48h before ovulation :

NOT affected by level of food intake

…..and so …..

Intake
hypothetical ewe
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

slide19

If there is only one large follicle present, it doesn’t matter how good the premating nutrition is, there cannot be more than one ovulation!

slide22

Probably by the LH pulse frequency during the 3 days before ovulation – high intake = more frequent pulses- low intake = less frequent pulses

slide23

BUT this difference in LH pulse frequency operates against a background of different nutrient and hormone signals within the follicle (leptin? )

when does nutrition determine lambing rate24
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 (?!)
it s not about
It’s 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

slide27
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

slide28
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
late pregnancy lactation
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)
mid pregnancy
Mid-pregnancy
  • Effects on gonad structure and function
  • (Rae et al. (2001, 2002)
slide35
How?
  • Nutrient delivery
nutrient delivery
Nutrient delivery

Maternal Undernutrition

Maternal Overnutrition

Normal Placenta

Small Placenta

Litter “Runt”

All affect reproductive development

slide37
How?
  • Nutrient delivery
  • Endocrine signals
slide38

Endocrine signals

Maternal Undernutrition

Maternal Overnutrition

Normal Placenta

Small Placenta

All change with nutritional state

All directly affect gonad function

All present and active in brain

other candidates
Other Candidates
  • Growth hormone
  • Cortisol
  • Glucagon
  • Prolactin
  • Ghrelin
  • Progesterone
  • Etc.
what evidence is there that
What Evidence Is There That…
  • early life nutrition can alter profiles of these hormones
  • the hormones can affect reproductive development
slide41

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
slide42
How?
  • Nutrient delivery
  • Endocrine signals
  • Structure and physiology
slide44
How?
  • Nutrient delivery
  • Endocrine signals
  • Structure and physiology
  • Reproductive behaviour
reproductive behaviour effects
Reproductive Behaviour Effects?
  • Normal:
  • Offspring of undernourished ewes:

• Demasculinisation of some non- reproductive behaviours

• By extrapolation - reduced sexual capacity?

slide46
How?
  • Nutrient delivery
  • Endocrine signals
  • Structure and physiology
  • Reproductive behaviour
  • Cellular level effects
effects at cellular level
Effects At Cellular Level
  • Effects can be expressed on very early embryos
effects at cellular level48
Effects At Cellular Level
  • Effects can be expressed on veryearly embryos
  • Modified expression of multiple genes
slide49

Effects At Cellular Level

  • Effects can be expressed on veryearly embryos
  • Modified expression of multiple genes
  • DNA methylation altered by nutrition
slide50

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

slide51
Transgenerational effects mean that the reproductive performance of animals is determined before they are conceived!
additional effects
Additional effects
  • Reproductive function
  • Altered thyroid function
additional effects54
Additional effects
  • Reproductive function
  • Altered thyroid function
  • Increased cardiovascular disease
additional effects55
Additional effects
  • Reproductive function
  • Altered thyroid function
  • Increased cardiovascular disease
  • Altered neuroendocrine development
additional effects57
Additional effects
  • Reproductive function
  • Altered thyroid function
  • Increased cardiovascular disease
  • Altered neuroendocrine development
  • Impaired glucose tolerance / diabetes
conclusions
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