Understanding the molecular basis for sperm function: the sperm connecting piece and sperm motility

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Spermatozoa are motile cells that transfer the father's genetic information to the oocyte. To function, sperm morphology must be normal, and sperm must acquire motility. Often, animal (and human) male infertility is related to abnormal sperm morphology and function. One phenotype, commonly observed for non-functional sperm, is sperm head detachment caused by a "fragile" sperm connecting piece. For cattle industry, high bull fertility is important and of economic consequence. We have discovered and characterized a sperm protein, p12 conserved among animal species, encoded by ornithine decarboxylase antizyme 3, Oaz3 gene. p12 modulates protein phosphatase activity, an important regulator of sperm motility. In sperm tails p12 likely regulates sperm tail motility but it is also present in the connecting piece. A mouse model shows that lack of p12 causes a fragile connecting piece phenotype and abnormal tail motility. This phenotype closely resembles observations made in the bovine industry.We propose to investigate how p12 is involved in regulation of sperm tail motility and in the connecting piece. We will a) analyze to which proteins p12 binds in the connecting piece, b) analyze if p12 regulates phosphorylation of connecting piece proteins, c) the importance of the association of p12 with Mypt3 on phosphatase activity in the sperm tail and regulation of motility, and d) analyze p12 function in sperm tail motility using novel transgenic mouse models for p12 using specific p12 mutant proteins.Our experiments will address a common problem in the cattle industry, and will provide tools to equip industry using reproductive technologies to diagnose sperm and optimize procedures.