New Study Reveals Epigenetic Links in PCOS Embryos for Early Diagnosis

In a groundbreaking study presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), researchers have uncovered significant epigenetic changes in the embryos of women with polycystic ovary syndrome (PCOS). This research sheds light on the potential for early risk detection and new therapeutic avenues in fertility treatments. The findings were published in the journal Human Reproduction on July 7, 2025.

Polycystic ovary syndrome is a common hormonal disorder affecting women of reproductive age and is often characterized by irregular menstrual periods, excess androgen levels, and polycystic ovaries. Despite its prevalence, the molecular origins of PCOS remain largely obscure. Dr. Qianshu Zhu, a leading researcher and assistant professor at the University of California, Irvine, noted that their study revealed a distinctive “epigenetic memory” in embryos, which may explain the hereditary nature of PCOS.

The study examined embryos from 133 women diagnosed with PCOS and compared them to embryos from 95 infertile women without the condition. The researchers utilized ultra-low-input sequencing to assess gene activity and epigenetic modifications. They specifically focused on histone modifications, particularly H3K27me3, H3K4me3, and H3K9me3, which are crucial for gene expression regulation. According to Dr. Zhu, “about half of the abnormal H3K27me3 signatures we saw in Day 3 embryos were already present in the oocyte, indicating that an epigenetic signal is being passed from mother to embryo before implantation begins.”

The implications of these findings are profound. The identification of abnormal histone marks in the embryos of affected women opens pathways for innovative diagnostic methods. Currently, diagnosing PCOS relies on hormone levels and ultrasound assessments of ovarian morphology. However, incorporating epigenetic profiling, especially focusing on H3K27me3 patterns, may facilitate earlier risk assessments for offspring of affected mothers.

Additionally, the research team explored potential therapeutic interventions. They found that levels of the abnormal H3K27me3 could be decreased using two specific PRC2 inhibitors, EED226 and valemetostat, in vitro. Dr. Zhu emphasized, “This provides new opportunities to evaluate embryos and potentially provide intervention.”

The study's findings align with other recent research highlighting the genetic and cellular alterations associated with PCOS. A complementary study published in Nature Medicine in March 2025 examined gene expression and cellular composition in the uterine lining of women with and without PCOS. This study identified distinct gene expression patterns in specific cell types, providing crucial insights for developing targeted treatments for PCOS-related endometrial dysfunction.

Dr. Karen Sermon, Chair of ESHRE, stated, “These findings allow for improved understanding and provide new treatment opportunities.” She emphasized the potential for future research to confirm whether altering histone marks could indeed transform PCOS traits in subsequent generations.

The researchers plan to conduct further studies using mouse models to investigate whether the manipulation of key genes can replicate PCOS-like traits in offspring. Such advancements could pave the way for preventive strategies against PCOS, potentially addressing the condition at its molecular roots.

As the scientific community continues to unravel the complexities of PCOS, these epigenetic insights may play a crucial role in shaping future fertility treatments and diagnostic practices, offering hope to countless women impacted by this condition.