Illustration of enlarged ovaries in someone with polycstic ovary syndrome
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Polycystic ovary syndrome may be passed down through families via chemical tags that change the structure of DNA, suggesting that drugs that modify these tags in embryos could prevent the condition.
People with polycystic ovary syndrome (PCOS) have at least two of three key features: high levels of male sex hormones such as testosterone, irregular periods or none at all, and a build-up of immature eggs – that appear like cysts – on their ovaries.
The condition often runs in families, but it isn’t clear exactly how it is inherited. “About 25 to 30 [genetic mutations] have been linked to PCOS, but that explains just a small fraction of the inheritance,” says Elisabet Stener-Victorin at the Karolinska Institute in Sweden.
Studies in mice suggest that changes in epigenetic marks – chemical tags that turn genes on and off without altering DNA sequences – may also play a role. It is thought most such marks are erased when eggs form, but some are thought to remain, a potential form of inheritance.
To see if this occurs in connection with PCOS in humans, Qianshu Zhu at Chongqing Medical University in China and his colleagues analysed epigenetic marks in eggs and 3-day-old embryos donated by 133 people with PCOS and 95 without the condition. “No one has really done it in this way in human material,” says Stener-Victorin.
This revealed a link between being a donor with PCOS and changes in patterns of three types of epigenetic marks in the eggs and embryos. Two of these marks turn genes off by making DNA coil more tightly around proteins called histones, which help package it within cells. This makes the genetic code in DNA less accessible to molecules that transcribe it into RNA, a key step in making proteins. The third type of mark activates genes by loosening DNA coils.
Together, the PCOS-linked epigenetic changes altered the metabolism of eggs and embryos, suggesting they may raise the risk of PCOS in offspring. But further studies should explore how they affect PCOS symptoms in the offspring of mice and humans, says Stener-Victorin. “For now, we just know that those marks are different; it does not necessarily mean they have a negative effect,” she says.
In another experiment, the team used a drug to reverse the epigenetic changes, suggesting this could reduce PCOS risk. “If we confirm that altering these histone marks changes PCOS traits in the next generation, we’ll have a powerful target for prevention,” Zhu said in a press release. What’s more, the team says that clinicians could potentially use PCOS-related epigenetic marks to select the healthiest embryos during in vitro fertilisation.
Zhu is presenting the results at the annual meeting of the European Society of Human Reproduction and Embryology in Paris on 1 July.
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