Epigenetic signature hints at why PCOS runs in families

The DNA of embryos from women with polycystic ovary syndrome (PCOS) carry specific epigenetic changes, according to research presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Paris.

PCOS, is a leading cause of subfertility and often associated with metabolic problems. It has been observed to run in families, but a genetic basis for it has never been found. In this study, a team of researchers in China compared egg cells and pre-implantation embryos from women with and without PCOS. They found multiple differences linked to three histone markers that control expression of genes in embryonic development.

'Importantly, about half of the abnormal [histone marker] signatures we saw in day three embryos were already present in the oocyte', said study leader Dr Qianshu Zhu from the Institute of Reproductive Medicine, Chongqing Medical University in China. 'This tells us that an epigenetic signal is being passed from mother to embryo before implantation even begins.'

Dr Zhu and his team looked at eggs and embryos stored by women undergoing fertility treatment, of whom 133 had PCOS and 95 did not. They analysed gene expression, as well as as epigenetic changes that affect whether genes are turned on or off.

In the samples from women with PCOS they found significant differences in the activity of genes related to early embryonic development, metabolism and epigenetic regulation. In addition, there were changes to chromatin and retrotransposons – elements that support the structure and stability of the genome itself.

All of these elements were linked to the three histone markers previously mentioned. One of these, called H3K27me3, can be targeted using drugs. In the lab, this approach reduced the abnormal levels and partially restored normal gene activity.

'We were surprised to find that H3K27me3, which is a histone mark best known in cancer biology, could also be an inherited driver of PCOS,' said Dr Zhu. 'It opens a new window for embryo assessment.'

Professor Karen Sermon, outgoing chair of ESHRE, commented: 'PCOS remains largely unsolved as to the molecular origins of the disease, and these findings on a large number of oocytes and embryos from affected women open a new avenue for its understanding and even treatment.'

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Professor Karen Sermon is both speaking at and chairing sessions at this year's PET Annual Conference, What Does Genomics Mean for Fertility Treatment?.

Find out more and register here.