O-GlcNAc participates in the meiosis of aging oocytes by mediating mitochondrial function.

Autor: Chuwei Li, Zhang Qian, Hong Zhang, Xie Ge, Li Chen, Mengqi Xue, Ting Tang, Zhaowanyue He, Lu Zheng, Chun Cao, Kemei Zhang, Rujun Ma, Bing Yao
Předmět:
Zdroj: Reproduction; Dec2024, Vol. 168 Issue 6, p45-56, 12p
Abstrakt: With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases; yet, it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (9 months), which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 to mediate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and Oga knockdown (Oga-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 weekold mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index