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Nutritional effects on ovarian function in monovulatory species: a new hypothesis

Reference	BB/C516479/1
Principal Investigator / Supervisor	Professor Bruce Campbell
Co-Investigators / Co-Supervisors	Dr Nigel Kendall, Professor Rex John Scaramuzzi
Institution	University of Nottingham
Department	Div of Obs & Gynaecology
Funding type	Research
Value (£)	268,337
Status	Completed
Type	Research Grant
Start date	01/10/2005
End date	28/02/2009
Duration	41 months

Abstract

Nutrition is a key environmental factor affecting reproduction but our understanding of the physiological mechanisms that underlie these effects is fragmentary and therefore this mechanism remains one of the major unsolved questions in reproductive physiology. Providing extra nutrition just before mating (flushing) has long been known to stimulate extra ovulations in sheep and it is well established that feeding lupins for as short a period as 4 days will stimulate extra ovulations. Recent data from our laboratory has shown that this effect occurs independently of pituitary gonadotrophins and some metabolic hormones. Lupins are known to contain a very high content of the monosacharide galactose and it is our hypothesis that it is this galactose that is responsible for stimulating ovarian function. Acting either directly on the ovary or through modulation of the insulin IGF system. This hypothesis is supported by the fact that disorders in galactose metabolism are known to lead to infertility in women and our own preliminary data showing that galactose, along with glucose, can directly affect the proliferation and steroid secretion of cultured sheep granulosa cells. Further, we have shown that circulating galactose concentrations are low in sheep on straw diets and that this sugar is rapidly cleared from the circulation following a bolus injection. We propose to investigate this hypothesis using our own highly developed and unique in vitro and in vivo model system. The possibility of direct ovarian effects will be investigated initially using the ovarian autotransplant model in which doses of glucose and galactose that will not alter systemic concentrations because lower doses can in infused directly in to the ovary thus bypassing the systemic circulation. These in vivo studies will be complemented by extension of our initial in vitro investigations to examine mechanistic aspects of galactose action on follicular somatic cell function and its interaction with glucose. Finally, the possibility that galactose is affecting ovarian function indirectly through modulation of the insulin IGF system will be investigated by an experiment utilising normal ewes without an autotransplant. They will be fed lupins or treated systemically with doses of intravenous glucose and galactose which would be expected to have systemic effects on pancreatic insulin secretion, hepatic IGF-I secretion as well as effects on hypothalamo-pituitary and ovarian function. The major endpoints of these studies will include the pattern of follicle development (in vivo), activity and level of expression of components of the insulin and the IGF systems (in vivo and in vitro), activity and level of expression of markers of somatic cell differentiation (in vivo and in vitro) and cellular proliferation and protein and mRNA expression of sugar transporters and glucose and galactose metabolic enzymes (in vitro). Of the sugar transporters, GLUT1 and GLUT4 have been chosen for study as the first is facultative and not dependent on insulin while the second is induced by insulin.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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