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

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.