Reproduction Abstracts

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that presents in women of reproductive age. The aetiology of PCOS is poorly understood, however it is likely that women with this disorder are predisposed to produce excess androgen at or well before puberty. Environmental and lifestyle factors then contribute to the multifarious symptoms observed. One such key external factor is diet. These studies utilised a prenatally exposed androgen mouse model to investigate i) the effect of foetal exposure to excess androgen and ii) the effect of a high fat modern diet, on factors and mechanisms that underpin PCOS and determine its severity.

Pregnant C57BL/6 mice were given daily subcutaneous injections of 250 μg DHT or sesame oil on days 15, 16, and 17 of gestation. At weaning, female pups from each DHT/control litter were randomly separated into cages with either standard chow or a 60% high fat diet and maintained for 6 weeks. Animals and food intake were monitored weekly and at the end of the study glucose tolerance tests were performed after an overnight fast before animals were sacrificed and tissues and plasma were harvested.

Prenatally androgenised mice fed a high fat diet gained significantly more weight than litter mates on a standard chow diet or control mice, on either diet (P<0.01). Mice fed a high fat diet were glucose intolerant compared to mice fed a normal chow diet (P<0.0001) but prenatal androgenisation alone did not affect blood concentrations.

In conclusion, this study provides strong evidence to support the notion that exposure to excess androgen during early development predisposes to metabolic characteristics of PCOS. Furthermore, a high fat diet is a key interacting factor that results in even greater weight gain and obesity than either prenatal androgen exposure or a high fat diet alone.