Is AMP-Activated Protein Kinase associated to the metabolic changes in Primary Ovarian Insufficiency?

Primary Ovarian Insufficiency (POI) is a critical fertility defect characterized by anticipated impairment of the follicular reserve which pathophysiological mechanisms have not yet been identified. We have investigated the possible relationship between AMPK and the pathophysiology of POI. We studied thirty-five POI patients with altered levels of FSH and estradiol and increased percentage of overweight compared with twenty healthy women. Blood mononuclear cells (BMCs) from POI patients showed reduced levels of phosphorylated AMPK, ATP, and high serum levels of leptin and TNF-alpha. All this alterations were also observed in granulosa cells, a more closer environment of the ovary. Significant negative correlations between AMPK and BMI, FSH and leptin levels, and a positive correlation between AMPK with estradiol levels were observed. Oral metformin supplementation restored biochemical parameters. Interestingly, AMPK levels from patients were negatively correlated with age suggesting an accelerated aging in POI mediated by the impairment of AMPK. These results lead to the hypothesis that an impairment of AMPK could be implicated in the metabolic pathophysiology of POI indicating at AMPK induction as a possible new therapeutic target.