(no more than 30 lines) Mammalian sperm acquire fertilization capacity as they transit through the reproductive tract in a process known as capacitation. During capacitation, sperm change their motility pattern and become competent to undergo an acrosome reaction and fertilize an egg. Capacitation-associated processes require energy. Similar to somatic cells, sperm generate ATP and other high energy compounds using nutrients in their surroundings via the coordinated actions of numerous metabolic pathways, including glycolysis and mitochondrial oxidative phosphorylation. In sperm, it remains unclear how these pathways are coordinately regulated to generate sufficient energy for motility and capacitation. In this application, we propose to apply modern metabolite profiling combined with metabolic flux analysis to sperm physiology to identify the contributions of the different metabolic pathways used by sperm. These studies will test the central hypothesis that sperm actively up-regulate their metabolism during capacitation to generate sufficient energy for motility and other capacitation- associated processes necessary for fertilization. Soluble adenylyl cyclase (sAC) is essential for the molecular changes observed during capacitation. In other contexts, sAC is a metabolic sensor. Therefore, we will also test the hypothesis that sAC acts as a metabolic sensor in sperm which regulates the metabolic changes induced by capacitation, and regulates energy production during sustained sperm motility. !
(no more than 3 sentences) To fertilize an egg, sperm must undergo a post-ejaculation maturation process and swim long distances. Both of these processes consume a lot of energy. In this application, we propose to identify how sperm gain sufficient energy to complete their maturation and reach the egg.