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Updated: May 26, 2025

Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Caloric restriction prevents inheritance of polycystic ovary syndrome through oocyte-mediated DNA methylation
Yue Liu1, Yi Dong2, Yonghui Jiang2
1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, The Second Hospital, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, Shandong, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250012, Shandong, China; Center for Reproductive Medicine, Gusu School, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, Nanjing 212028, Jiangsu, China.
Abstract:
Polycystic ovary syndrome (PCOS) is a prevalent metabolic and reproductive endocrine disorder with strong heritability. However, the independent role of oocytes in mediating this heritability remains unclear. Utilizing in vitro fertilization-embryo transfer and surrogacy, we demonstrated that oocytes from androgen-exposed mice (F1) transmitted PCOS-like traits to F2 and F3 generations. Notably, caloric restriction (CR) in F1 or F2 effectively prevented this transmission by restoring disrupted DNA methylation in oocyte genes related to insulin secretion and AMPK signaling pathways. Further detection in adult tissues of offspring revealed dysregulated DNA methylation and expression of those genes (e.g., Adcy3, Gnas, and Srebf1) were reversed by maternal CR. Moreover, similar benefits of CR were observed in aberrant embryonic methylome of women with PCOS. These findings elucidate the essential role of CR in preventing PCOS transmission via methylation reprogramming, emphasizing the importance of preconception metabolic management for women with PCOS.
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