A deletion of AMPK in human granulosa cells (KGN) by Crispr/cas9 strategy was performed. An analysis by RNAseq analysis was realised on KGN AMPK mutant (KO-KGN cells, n = 10) and KGN control cells (Scr-KGN cells, n = 10). In each group 5 samples were untreated and 5 samples treated with delphinidin (a polyphenol). Details of the construction and cells exposure can be found in the publication associated with this study.

The interaction between metabolism and female fertility is critical. For example, polycystic ovarian syndrome (PCOS) affects 5-20% women of reproductive age and induces an infertility associated frequently with insulin resistance, hyperandrogenism, and chronic inflammation. Here we analyzed the role of AMP-activated protein kinase (AMPK), one of the main regulators of energy homeostasis. Food intake and energy expenditure are modulated by AMPK activity in response to hormonal and nutritional cues in the central nervous system and peripheral tissues, including the reproductive system. As infertility is frequently associated with hormonal imbalances and metabolic disorders, here we investigated the role of the a1 isoform AMPK (a1AMPK) in human granulosa cell function. Silencing of a1AMPK in immortalized human granulosa cells increased cell proliferation, promoted the use of fatty acids over glucose, and induced a hyperandrogenic response. The RNAseq analysis has shown a dysregulation in gene expression involved in cell cycle, cell adhesion, lipid metabolism and steroidogenesis. Our study supports the notion that deficiency in a1AMPK (due to environmental factors, genetics, or their combination) plays an important role in female reproduction, especially in granulosa cells.