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Dysregulated epigenetic memory in early embryos offers new clues to the inheritance of polycystic ovary syndrome (PCOS)

Novel research has found that embryos from women with polycystic ovary syndrome (PCOS) carry a distinctive ‘epigenetic memory’ that could explain why the condition often runs in families

2025-06-30
(Press-News.org) (Paris, France, Tuesday, 1 July 2025) Novel research presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) has found that embryos from women with polycystic ovary syndrome (PCOS) carry a distinctive ‘epigenetic memory’ that could explain why the condition often runs in families.[1]

PCOS is a common hormonal disorder affecting an estimated 1 in 10 women of reproductive age worldwide.[2] It is characterised by irregular menstrual cycles, excess levels of androgens (male hormones) and the presence of multiple cysts on the ovaries.[3] While it is recognised as a leading cause of infertility, the exact causes and mechanisms of inheritance remain unclear.[4]

The study, led by Dr. Qianshu Zhu, analysed oocytes and pre-implantation embryos from 133 PCOS patients and 95 non-PCOS infertile women undergoing fertility treatment. The team used ultra-low-input sequencing to analyse both gene activity and epigenetic changes – chemical tags that regulate how genes turn on and off without altering the underlying DNA sequence.

The research revealed widespread disruptions in the activity of genes responsible for early embryonic genome activation, metabolic processes, epigenetic regulation, and chromatin structure in embryos from women with PCOS. These disruptions also affected retrotransposons – mobile DNA elements usually tightly regulated to maintain genomic stability – further highlighting how early developmental programming is affected.

These abnormalities were closely linked to irregular patterns of three histone marks that play a key role in controlling gene expression: H3K27me3, H3K4me3 and H3K9me3.

“Importantly, about half of the abnormal H3K27me3 signatures we saw in Day 3 embryos were already present in the oocyte”, said Dr. Zhu. “This tells us that an epigenetic signal is being passed from mother to embryo before implantation even begins.”

Treating affected embryos in vitro with two PRC2 inhibitors (EED226 and valemetostat) reduced abnormal H3K27me3 levels and partially restored normal gene activity, suggesting a potential therapeutic avenue for correcting epigenetic imbalances.

“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”, Dr. Zhu noted. “It opens a new window for embryo assessment and perhaps even intervention.”

Currently, PCOS diagnostics focus on hormone levels and ovarian morphology. Epigenetic profiling, particularly of H3K27me3, could eventually complement these tools, offering earlier risk assessment for offspring conceived by affected mothers. In assisted reproductive technologies (ART), H3K27me3 patterns may even serve as biomarkers for embryo selection during IVF, potentially improving the success of fertility treatments.

Dr. Zhu cautioned that the work is based on laboratory-grown embryos and does not yet prove long-term effects in children. The team’s next step is to validate the findings in mouse models by knocking down the Kdm6a and Kdm6b genes, which remove H3K27me3, to investigate whether offspring develop PCOS-like traits.

“If we confirm that altering these histone marks changes PCOS traits in the next generation, we’ll have a powerful target for prevention”, he said.

Prof. Dr. Karen Sermon, 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.”

The study abstract will be published today in Human Reproduction, one of the world’s leading journals in reproductive medicine.

 

ENDS

 

Notes to editors:

A reference to the ESHRE Annual Meeting must be included in all coverage and/or articles associated with this study.

For more information or to arrange an expert interview, please contact the ESHRE Press Office at: press@eshre.eu

About the study author:

Dr Qianshu Zhu MD, PhD is an assistant professor of reproductive biology at the Institute of Reproductive Medicine, Chongqing Medical University in China. His research centres on how epigenetic reprogramming in human oocytes and early embryos influences fertility and the intergenerational transmission of disorders such as polycystic ovary syndrome (PCOS). Dr Zhu leads a multidisciplinary laboratory that combines single-cell sequencing, embryo culture and CRISPR-based chromatin editing, and he has authored or co-authored more than 14 peer-reviewed papers in journals including Nature Communications and Nucleic Acids Research.

About the European Society of Human Reproduction and Embryology

The main aim of ESHRE is to promote interest in infertility care and to aim for a holistic understanding of reproductive biology and medicine.

ESHRE collaborates world-wide and advocates universal improvements in scientific research, encourages and evaluates new developments in the field, and fosters harmonisation in clinical practice. It also provides guidance to enhance effectiveness, safety and quality assurance in clinical and laboratory procedures, psychosocial care, and promotes ethical practice. ESHRE also fosters prevention of infertility and related educational programmes and promotes reproductive rights regardless of the individual’s background. ESHRE’s activities include teaching, training, professional accreditations, mentoring and career planning for junior professionals, as well as developing and maintaining data registries. It also facilitates and disseminates research in human reproduction and embryology to the general public, scientists, clinicians, allied personnel, and patient associations.

Website: https://www.eshre.eu/

About Human Reproduction

Human Reproduction is a monthly journal of ESHRE and is one of the top three journals in the world in the field of reproductive biology, obstetrics and gynaecology. It is published by Oxford Journals, a division of Oxford University Press.

References:

[1] Zhu Q., et al. (2025). Dysregulated Epigenetic Reprogramming During Pre-implantation Development of Embryos from Patients with Polycystic Ovary Syndrome. Human Reproduction. 

[2] Zeng, L. H., et al. (2022). Polycystic Ovary Syndrome: A Disorder of Reproductive Age, Its Pathogenesis, and a Discussion on the Emerging Role of Herbal Remedies. Frontiers in pharmacology, 13, 874914. https://doi.org/10.3389/fphar.2022.874914

[3] NHS. (2022). Polycystic ovary syndrome (PCOS). https://www.nhs.uk/conditions/polycystic-ovary-syndrome-pcos/

[4] World Health Organization. (2025). Polycystic ovary syndrome. https://www.who.int/news-room/fact-sheets/detail/polycystic-ovary-syndrome

END



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[Press-News.org] Dysregulated epigenetic memory in early embryos offers new clues to the inheritance of polycystic ovary syndrome (PCOS)
Novel research has found that embryos from women with polycystic ovary syndrome (PCOS) carry a distinctive ‘epigenetic memory’ that could explain why the condition often runs in families