Written By: IJCP Editorial Team

Published On: 25 Mar, 2025 12:42 PM | Updated On: 26 Mar, 2025 10:12 AM

Caloric Restriction Mitigates Hereditary Transmission of PCOS Traits Through Methylation Reprogramming

Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive endocrine disorder that has a strong genetic component. However, the specific role of oocytes in passing on this heritability is not well understood. Through in vitro fertilization-embryo transfer and surrogacy studies, we found that oocytes from mice exposed to androgens (F1 generation) could pass on PCOS-like characteristics to the second (F2) and third (F3) generations. Importantly, implementing caloric restriction (CR) in either the F1 or F2 generations effectively halted this transmission by correcting abnormal DNA methylation in genes associated with insulin secretion and AMPK signaling in oocytes. Further analysis of adult tissues in the offspring revealed that the altered DNA methylation and gene expression of specific genes (such as Adcy3, Gnas, and Srebf1) were normalized through maternal CR. Additionally, women with PCOS exhibited similar improvements in the abnormal embryonic methylation patterns. These results highlight the crucial role of caloric restriction in preventing the inheritance of PCOS through methylation changes, underscoring the need for metabolic management before conception for women affected by PCOS.

Source: Liu Y, Dong Y, Jiang Y, Han S, Liu X, Xu X, Zhu A, Zhao Z, Gao Y, Zou Y, Zhang C, Bian Y, Zhang Y, Liu J, Zhao S, Zhao H, Chen ZJ. Caloric restriction prevents inheritance of polycystic ovary syndrome through oocyte-mediated DNA methylation reprogramming. Cell Metab. 2025 Feb 11:S1550-4131(25)00014-2. doi: 10.1016/j.cmet.2025.01.014. Epub ahead of print. PMID: 39986273.