title: Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function.
abstract: Reactive oxygen species (ROS) are known to play an important role in the regulation of human sperm function. In this study, we demonstrate for the first time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an l-amino acid oxidase (LAAO) which is capable of generating ROS on exposure to aromatic amino acids in the presence of oxygen. The preferred substrates were found to be phenylalanine and tryptophan while the enzyme was located in the acrosomal region and midpiece of these cells. In contrast to equine and bovine spermatozoa, enzyme activity was lost as soon as the spermatozoa became non-viable. On a cell-to-cell basis human spermatozoa were also shown to generate lower levels of hydrogen peroxide than their equine counterparts on exposure to phenylalanine. Stimulation of LAAO activity resulted in the induction of several hallmarks of capacitation including tyrosine phosphorylation of the sperm flagellum and concomitant activation of phospho-SRC expression. In addition, stimulation of LAAO resulted in an increase in the levels of acrosomal exocytosis in both the presence and absence of progesterone stimulation, via mechanisms that could be significantly reversed by the presence of catalase. As is often the case with free radical-mediated phenomena, prolonged exposure of human spermatozoa to phenylalanine resulted in the stimulation of apoptosis as indicated by significant increases in mitochondrial superoxide generation and the activation of intracellular caspases. These results confirm the existence of an LAAO in human spermatozoa with a potential role in driving the redox regulation of sperm capacitation and acrosomal exocytosis.
authors.affiliation: Discipline of Biological SciencesSchool of Environmental and Life Sciences, Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Houston
authors.affiliation: Discipline of Biological SciencesSchool of Environmental and Life Sciences, Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Curry
authors.affiliation: Discipline of Biological SciencesSchool of Environmental and Life Sciences, Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, New South Wales 2308, Australia john.aitken@newcastle.edu.au.
authors.forename: R J
authors.initials: RJ
authors.lastname: Aitken
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050830:L-Amino Acid Oxidase / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000494:pharmacology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013075:Sperm Capacitation / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D010649:Phenylalanine; D050830:L-Amino Acid Oxidase