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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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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. • Domestic animals –More offspring = more money!
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 • 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? • 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? • During gestation – loss of embryos
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 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 rate? • During gestation – loss of embryos • Days, weeks, months and years before mating – ovulation rate
Short term intake effects and medium term body condition effects are NOT expressed through the same physiological mechanisms
Body condition Numbers of large, potentially ovulatory, ovarian follicles at 48h before ovulation : High body condition (HBC) 4 Low body condition (LBC) 2
Numbers of large, potentially ovulatory, ovarian follicles at 48h before ovulation : NOT affected by level of food intake …..and so ….. Intake
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
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!
How is the rate of feed intake signalled to the ovary in the ewe?
Probably by the LH pulse frequency during the 3 days before ovulation – high intake = more frequent pulses- low intake = less frequent pulses
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 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 (?!)
Effects of fetal nutrition on adult reproductive performance.
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
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
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 • 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 • Effects on gonad structure and function • (Rae et al. (2001, 2002)
How? • Nutrient delivery
Nutrient delivery Maternal Undernutrition Maternal Overnutrition Normal Placenta Small Placenta Litter “Runt” All affect reproductive development
How? • Nutrient delivery • Endocrine signals
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 • Growth hormone • Cortisol • Glucagon • Prolactin • Ghrelin • Progesterone • Etc.
What Evidence Is There That… • early life nutrition can alter profiles of these hormones • the hormones can affect reproductive development
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
How? • Nutrient delivery • Endocrine signals • Structure and physiology
Structure and Physiology Type 2 follicles /mm2 - 110d fetus
How? • Nutrient delivery • Endocrine signals • Structure and physiology • Reproductive behaviour
Reproductive Behaviour Effects? • Normal: • Offspring of undernourished ewes: • Demasculinisation of some non- reproductive behaviours • By extrapolation - reduced sexual capacity?
How? • Nutrient delivery • Endocrine signals • Structure and physiology • Reproductive behaviour • Cellular level effects
Effects At Cellular Level • Effects can be expressed on very early embryos
Effects At Cellular Level • Effects can be expressed on veryearly embryos • Modified expression of multiple genes
Effects At Cellular Level • Effects can be expressed on veryearly embryos • Modified expression of multiple genes • DNA methylation altered by nutrition
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