Follicular disorders, often driven by ROS-induced granulosa cell apoptosis, are a major cause of female infertility. While α-ketoglutarate (AKG), also known as 2-oxoglutarate, can improve follicular development, the underlying mechanisms remain unclear. Given that AKG is the primary substrate of oxoglutarate dehydrogenase (OGDH), this study aimed to investigate how OGDH mediates the protective role of AKG against oxidative stress and in supporting follicular development. AKG treatment advanced puberty onset and increased the number of corpora lutea in mice. It alleviated oxidative stress and apoptosis in granulosa cells by upregulating CAT and downregulating P53. Crucially, OGDH physically interacted with CAT and SOD2 and boosted their enzymatic activities, thereby reinforcing AKG’s antioxidative effects. Knockdown of OGDH markedly impaired the ability of AKG to promote follicular development. These findings identify OGDH as a key mediator of AKG’s protective role in follicular development through modulation of oxidative stress and apoptosis. This work provides mechanistic insight into AKG function and supports its potential as a therapeutic strategy for follicular disorders.
Huang et al. (Fri,) studied this question.