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Title: The role of insulin-like growth factors and anti-Müllerian hormone in early follicle development in normal and polycystic ovaries
Author: Stubbs, Sharon Anne
ISNI:       0000 0004 2680 2888
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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Polycystic ovary syndrome (peOS) is the most common cause of anovulation in women of reproductive age. It has recently been shown that as well as abnormalities in the later stages of follicle development, there are also differences in development at the early preantral stages of follicle growth in polycystic ovaries. Specifically, aberrant preantral follicle development in polycystic ovaries is characterised by an increase in the proportion of growing follicles (and a reciprocal decrease in the proportion of primordial, resting follicles) compared to normal ovaries. Our hypothesis is that such abnormalities are due to either an increase in the production (or action) of insulin-like growth factors I or n, or a decrease in the production or action of the inhibitory growth factor AMH. Studies in experimental animals have shown that IGF-I is able to stimulate early folliculogenesis, and preliminary studies in primate pre antral follicles suggest that it may have a similar role in the human ovary. AMH-null mice have been shown to have an increased proportion of growing follicles and a reciprocally reduced proportion of primordial follicles. This phenotype is remarkably similar to that observed in tissue from human polycystic ovaries. The expression of members of the IGF family and TGF-~ superfamily have been studied using immunohistochemistry on formalin fixed, archived human ovarian tissue from normal and polycystic ovaries, and the effect of IGF-I on the initiation of follicle growth is investigated using cultures of human ovarian cortex. The type-l IGF receptor was identified at all stages of follicle development. IGF-I, at a dose as low as lng/ml, was shown to increase the proportion of growing follicles, an effect that was attenuated by adding an antibody to the type-l receptor. AMH immunostaining was examined in normal and polycystic ovaries and the most important finding was that a reduced proportion of follicles stained positively for AMH at the primordial and transitional stages in anovulatory polycystic ovaries. These data support the hypotheses that increased activity of IGFs and reduced expression of AMH (or both), have an important role in aberrant early preantral follicle development in the polycystic ovary.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available