Comparative studies on the regulation of metabolism during sperm capacitation

Summary/Abstract
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 oocyte. These capacitation-associated processes require
energy, and sperm are dependent on nutrients in their environment to complete
them. Sperm are exposed to different nutrients in their surroundings as they pass
from being stored in the cauda epididymis to the fallopian tube where they will meet
and fertilize the oocyte. In the previous funding period, we demonstrated that
sperm supplied with exogenous glucose generate ATP via glycolysis and oxidative
phosphorylation, and glucose utilization via both pathways increases in
capacitating sperm. In addition, we found that capacitating sperm alter activity
through the pentose phosphate pathway and sperm deprived of exogenous
nutrients can metabolize endogenous energy sources. We now propose to apply
modern metabolite profiling combined with metabolic flux analyses to identify how
sperm coordinately regulate their metabolic pathways and leverage different
exogenous nutrients as they mature through distinct activation states. Soluble
adenylyl cyclase (sAC) is essential for the molecular changes observed during
capacitation, and we will use our unique tools for modulating its activity to test the
hypothesis that sAC regulates the metabolic changes induced by capacitation.

Grant Number: 5R01HD088571-09
NIH Institute/Center: NIH
Principal Investigator: JOCHEN BUCK