AMPK an energy sensor involved in male fertility control – FERTiNERGY

In birds and mammals (including humans), nutrition and energy metabolism strongly influence reproduction. In agronomy and more particularly in poultry, the intense selection of chickens for meat production promotes rapid muscle development and leads to have a negative energy balance that affects fertility. At the organism level, detectors of energy levels indicate whether energy reserves are abundant (obesity), or poor (in case of food restriction, sport training…). One of the detectors is AMPK (5 'AMP-activated protein kinase), a protein kinase activated by the ATP deficit, but also by natural substances such as polyphenols or drug (metformin used in the treatment of insulin resistance). AMPK is expressed in muscle, liver, but also at the gonadotroph axis (hypothalamus, pituitary, ovary, testis). Several studies in females suggested a role of AMPK on fertility, as used in the treatment of infertility associated with insulin resistance (polycystic ovary syndrome), but no data are available in the male until now. However, our preliminary results using a pharmacological activator of AMPK (metformin) showed a delay in development of testicular function.
The goal of our project is to better understand the role of AMPK in the control of male reproduction and its interest in improving the fertility of animals of agricultural interest. This approach is based on the use of mice fed a diet supplemented with agonists of AMPK in the presence genetic background deficient or not for a1AMPK. AMPK will be inactivated either by Cre recombinase in the testis, either by expressing a dominant negative in brain (intracerebroventricular injection) in order to determine its role in the gonadal axis. Finally, a mechanistic study on cells cultured in vitro will help to define the molecular mechanisms of AMPK on testicular function. All these strategies should identify the potential role of AMPK (or its ligands) in male reproduction.