A large proportion of the affected genes are linked to difficulties for the early embryo to attach to the uterus, miscarriage, and endometrial cancer with functions affecting cell-to-cell attachment and communication.

“Our analyses show that certain cell types in the endometrium have disrupted communication and interaction specific to PCOS,” says Gustaw Eriksson, one of the study's first authors and a doctoral student in Elisabet Stener-Victorin's research group.

Underwent treatment with diabetes drug

The study also included a part where the women with PCOS underwent treatment with the diabetes drug metformin with or without lifestyle advice on diet and exercise. After 16 weeks of treatment, the researchers found that many gene expressions in specific cell types, especially in the epithelial and stromal cells, were normalised by metformin, but also by lifestyle changes, although not as pronounced.

“We can show that metformin seems to have many more functions in women with PCOS than lowering blood sugar. In the study, all the women were overweight, but it is likely that metformin has similar effects in affected women who are not overweight but insulin resistant if they have problems getting pregnant or have repeated miscarriages,” says Elisabet Stener-Victorin.

Another important finding was the correlation between gene expression in specific cell types and important clinical features of PCOS, such as elevated levels of male sex hormone and insulin resistance, highlighting the complex relationship between hormonal and metabolic factors and endometrial dysfunction. 

“As we identified changes in gene expression in specific cell types, this study provides crucial guidance for developing more targeted treatments for PCOS-related endometrial dysfunction,” says Elisabet Stener-Victorin.

The study is a collaboration with Dr Congru Li as joint first author, and Associate Professor Qiaolin Deng and Associate Professor Sophie Petropoulos with joint senior and corresponding authorship.

The research was funded by the Swedish Research Council, the Novo Nordisk Foundation, the Diabetes Foundation and the Knut and Alice Wallenberg Foundation, among others. The researchers declare that there are no conflicts of interest.