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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P159 | DOI: 10.1530/repabs.1.P159

Investigating whether Kiss1 KO mice can be used as a model for PCOS and age-onset diabetes

Victoria Kyle, Xavier d’Anglemont de Tassigny & William H Colledge


University of Cambridge, Cambridge, UK.


Polycystic ovary syndrome (PCOS) is generally thought to be a genetic disease, which affects 5–10% of women of reproductive age (approximately 11–47 years old). Typically, PCOS is characterized by the formation of cysts on the ovaries and ovulatory failure. Characteristically PCOS results in high levels of androgens such as testosterone and insulin resistance within the blood. The ovaries of Kiss1 mutant mice have been shown to frequently form multiple cysts (Lapatto et al., 2007, Endocrinology, 148:4927-4936) leading us to hypothesise that these mice might provide a model for PCOS. Mutant Kiss1 mice have hypogonadotrophic hypogonadism and fail to ovulate, which may contribute to cyst formation. To test this hypothesis, we compared androgen levels in12 month old Kiss1 mutant mice compared to age matched wild-type mice. Furthermore, the ovaries were collected for histological analysis to investigate the presence of cysts and immunohistochemical detection of proteins involved in the metabolism of androgens and estrogens. We also investigated glucose responses in these aged mice as it has recently been reported that kisspeptin production by the liver can impair insulin secretion (Song et al., 2014, Cell Metabolism 19:667-681). Serial tail bleeds after an injection of glucose were taken from wild type (n=14) and mutant mice (n=12) and assayed for glucose clearance and insulin levels. Kiss1 KO mice showed reduced clearance of glucose from the blood stream. We are currently investigating whether this results from impaired insulin release or insulin resistance.

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