HDAC6-Dependent Deacetylation of NGF Dictates Its Ubiquitination and Maintains Primordial Follicle Dormancy

January 2024 in “ Theranostics ”

Tuo Zhang, Yuntong Tong, Ruxin Zhu, Yao-Yun Liang, Jixian Zhang, Chujiao Hu, Meina He, Hongwei Zhu, Zhongzhou Shen, Jin Niu, Jingjing Zhang, Yuanyuan Yu, Bangming Jin, Lei Shan, Zhirui Zeng, Yinuo Wu, Zhongjun Cheng, Ziwen Xiao, Bing Guo, Shuyun Zhao, Guoqiang Xu, Wei Pan, Tengxiang Chen

HDAC6 histone deacetylase 6 NGF nerve growth factor primordial follicle dormancy granulosa cells RNA sequencing follicle activation reproductive aging fertility preservation

TLDR HDAC6 helps keep ovarian follicles dormant, extending female fertility.

The study investigates the role of histone deacetylase 6 (HDAC6) in maintaining primordial follicle dormancy and female fertility. Using human ovarian samples, granulosa cells from DOR patients, an Hdac6-overexpressing mouse model, and RNA sequencing, researchers found that HDAC6 is highly expressed in dormant primordial follicles and decreases with reproductive aging. Overexpression of Hdac6 delayed follicle activation, extending reproductive lifespan, while short-term HDAC6 inhibition promoted follicle activation. Mechanistically, HDAC6 interacts with NGF, reducing its acetylation and increasing its degradation, thus maintaining follicle dormancy. The findings highlight HDAC6's role in fertility preservation by regulating NGF levels.

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