Grant: Project Grant

The role of spermatozoa is to bring the paternal genetic content in close proximity to the maternal genetic content during fertilization. Sperm flagellar motility is required to bring themselves close to the egg, and their head must interact with the egg surface, bind and fuse with the egg membranes to finally deliver their nucleus inside the egg. Defects in any of these sperm events jeopardize the success of fertilization and might lead to male infertility. Spermatozoa are highly differentiated cells that are unable to multiply, to transcribe their genes and to synthetize new proteins. They must therefore rely on their own set of proteins, which they can modify through intracellular biochemical reactions, in order to successfully achieve their roles. Sperm motility and interaction with the egg are regulated by intracellular biochemical events. Intracellular agents like cyclic AMP, Ca2+, reactive oxygen species, trigger a cascade of signalling and biochemical events that will ultimately lead to the phosphorylation of proteins involved in sperm motility or in sperm interaction with the egg. Like every living cell, spermatozoa possess mitochondria, known as powerhouses generating the ATP necessary to various enzymatic activities and cell functions. In spermatozoa however, although motility requires a huge amount of ATP, the role of mitochondria in this cellular activity remains debatable. Extra-mitochondrial production of ATP through glucose metabolism is recognized as a significant player. It has been recently shown that STAT proteins positively affect cell mitochondria independently of their gene transcription activity. When sperm are incubated with STAT inhibitors, they lose their motility within 4 hours. Therefore, our goal is to better understand the regulatory mechanisms of mitochondria on sperm function and the importance of STAT proteins in sperm mitochondria. This study will help to determine the importance of sperm mitochondrial function in male fertility.