Grant: Discovery Grants Program - Individual

The molecules in the head of mammalian sperm must reorganise just prior to meeting the egg, in order to fertilise it. This reorganisation is started by signals that the sperm receives that cause the sperm to reorganise the membrane structure of its head and start specific internal reactions that enable the sperm to bind to and penetrate the egg. The exact nature of the signal(s), and how they are received, is unknown, making it difficult to improve the fertility of the male or to preserve sperm for artificial insemination. One molecule, Na/K-ATPase, is well known as an enzyme but recently was recognised as a membrane-bound signal receptor in some body cells. We showed that it also acts in sperm as a membrane receptor, sending signals into the sperm to start capacitation when its specific hormone ouabain binds to it. Na/K-ATPase is made of two subunits, each of which has several isoforms. Think of the isoforms of one subunit desktop, laptop or ipad computer, each requiring somewhat different methods to turn them on. The other subunit is a peripheral device, either a printer, scanner or webcam. Pairing any one computer isoform with any one peripheral isoform affects the function of the paired devices, and certainly changes its output. Similarly, isoforms and subunits in sperm Na/K-ATPase affect how it functions, and we hypothesize that good fertility really depends on having the correct pair of isoforms to have Na/K-ATPase perform optimally as a signal-receptor, just as you need to pair the correct computer and peripheral device to function smoothly, and efficiently produce the high-quality output you want. Since the subunits are proteins, and it is the membrane over the head of the sperm that first binds to the egg and where capacitation starts, over the 5 years of the research we will compare the specific amino acid structure of the subunits in the head membrane of sperm from high- and low-fertility bulls to identify which pairing is associated with the best fertility; whether it is the amount of isoform, or its structure, that influences fertility; and we will follow the signal's activation path in the sperm that ultimately permits fertilization. This serves the long-term objective, to be able to explain currently unexplained causes of infertility, to understand and be able to better protect, predict and improve sperm membrane molecules that impact fertility of sperm. Results will enable us to detect males with poor chances of fertility, and to design remediation methods that will protect those critical sperm membrane molecules. This will enhance reproductive success for domestic and endangered species, and potentially find application in human reproduction.