News | Embryos From Patients With PCOS Carry Distinct Epigenetic Memory, Offering Clues to Inheritance
At the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), researchers presented a study identifying a distinct "epigenetic memory" in embryos from women with polycystic ovary syndrome (PCOS). The finding may help explain why PCOS clusters in families.
PCOS is a common endocrine disorder affecting about 10% of reproductive-age women worldwide. Typical features include irregular menstruation, hyperandrogenism, and polycystic ovarian morphology. It is a major cause of infertility, but its genetic mechanisms and molecular basis remain unclear.
Early embryos carry abnormalities already present in oocytes
Led by Dr. Qianshu Zhu, the team analyzed oocytes and embryos from assisted reproduction cycles involving 133 patients with PCOS and 95 infertile women without PCOS. Ultra-low-input sequencing measured gene expression and epigenetic features at single-cell resolution.
Embryos from patients with PCOS showed systematic abnormalities in embryonic genome activation (EGA), metabolic pathways, chromatin structure, and epigenetic regulation. Retrotransposons were also abnormally activated, suggesting impaired stability early in embryonic development.
The changes were strongly associated with disruption of three key histone modifications:
H3K27me3, a classic transcriptional repression marker;
H3K4me3, an active promoter marker;
H3K9me3, a heterochromatin-associated marker.
Dr. Zhu said: "Nearly half of the H3K27me3 abnormalities observed in day-three embryos were already present in the oocytes, indicating transmission of maternal epigenetic signals to the next generation."
In vitro intervention partially reverses abnormalities
To test the mechanism, researchers treated embryos in vitro with two PRC2 complex inhibitors, EED226 and valemetostat. H3K27me3 levels declined, partially restoring normal gene-expression activity. The result suggests that epigenetic intervention might repair some embryo abnormalities during assisted reproduction.
"H3K27me3 has mainly been studied in cancer, but its possible role in transgenerational transmission of PCOS creates new possibilities for clinical embryo assessment and intervention," said Dr. Zhu.
H3K27me3 could become a marker for IVF embryo selection
PCOS diagnosis currently relies mainly on hormone levels and ovarian ultrasound findings. The team suggests that epigenetic markers such as H3K27me3 could eventually support earlier risk identification, embryo selection, and improved assisted reproduction outcomes.
Dr. Zhu emphasized that the study used laboratory-cultured embryos and cannot establish long-term effects on fetuses or infants. The team next plans to knock down Kdm6a and Kdm6b, H3K27me3 demethylases, in mice to determine whether PCOS-like traits appear.
"If modifying histone marks changes PCOS traits in the next generation, it could provide a highly promising molecular target for prevention."
ESHRE Chair Prof. Karen Sermon commented: "PCOS remains a molecular mystery. This systematic study of oocytes and embryos from many patients opens a new window into understanding and treating it."
The study abstract was published in Human Reproduction.
News | Embryos From Patients With PCOS Carry Distinct Epigenetic Memory, Offering Clues to Inheritance
News | Embryos From Patients With PCOS Carry Distinct Epigenetic Memory, Offering Clues to Inheritance
At the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), researchers presented a study identifying a distinct "epigenetic memory" in embryos from women with polycystic ovary syndrome (PCOS). The finding may help explain why PCOS clusters in families.
PCOS is a common endocrine disorder affecting about 10% of reproductive-age women worldwide. Typical features include irregular menstruation, hyperandrogenism, and polycystic ovarian morphology. It is a major cause of infertility, but its genetic mechanisms and molecular basis remain unclear.
Early embryos carry abnormalities already present in oocytes
Led by Dr. Qianshu Zhu, the team analyzed oocytes and embryos from assisted reproduction cycles involving 133 patients with PCOS and 95 infertile women without PCOS. Ultra-low-input sequencing measured gene expression and epigenetic features at single-cell resolution.
Embryos from patients with PCOS showed systematic abnormalities in embryonic genome activation (EGA), metabolic pathways, chromatin structure, and epigenetic regulation. Retrotransposons were also abnormally activated, suggesting impaired stability early in embryonic development.
The changes were strongly associated with disruption of three key histone modifications:
H3K27me3, a classic transcriptional repression marker;
H3K4me3, an active promoter marker;
H3K9me3, a heterochromatin-associated marker.
Dr. Zhu said: "Nearly half of the H3K27me3 abnormalities observed in day-three embryos were already present in the oocytes, indicating transmission of maternal epigenetic signals to the next generation."
In vitro intervention partially reverses abnormalities
To test the mechanism, researchers treated embryos in vitro with two PRC2 complex inhibitors, EED226 and valemetostat. H3K27me3 levels declined, partially restoring normal gene-expression activity. The result suggests that epigenetic intervention might repair some embryo abnormalities during assisted reproduction.
"H3K27me3 has mainly been studied in cancer, but its possible role in transgenerational transmission of PCOS creates new possibilities for clinical embryo assessment and intervention," said Dr. Zhu.
H3K27me3 could become a marker for IVF embryo selection
PCOS diagnosis currently relies mainly on hormone levels and ovarian ultrasound findings. The team suggests that epigenetic markers such as H3K27me3 could eventually support earlier risk identification, embryo selection, and improved assisted reproduction outcomes.
Dr. Zhu emphasized that the study used laboratory-cultured embryos and cannot establish long-term effects on fetuses or infants. The team next plans to knock down Kdm6a and Kdm6b, H3K27me3 demethylases, in mice to determine whether PCOS-like traits appear.
"If modifying histone marks changes PCOS traits in the next generation, it could provide a highly promising molecular target for prevention."
ESHRE Chair Prof. Karen Sermon commented: "PCOS remains a molecular mystery. This systematic study of oocytes and embryos from many patients opens a new window into understanding and treating it."
The study abstract was published in Human Reproduction.
Source:
Collected online