Nitric Oxide: A Double Edged Weapon for Sperm Functions

Abstract

) and hydroxyl (OH) radicals. Those derived from nitrogen are called reactive nitrogen species (RNS). RNS include nitric oxide (NO ), nitrogen dioxide (NO 2 ) and peroxynitrite anion (ONOO ). RNS are often considered to be a subclass of ROS. Recent information on the NO has proved its importance as an intercellular and intracellular messenger controlling many physiological processes. It is also a mediator of cytokines and growth factors in various cell types. NO is synthesized form L-arginine by the action of nitric oxide synthase (NOS), an enzyme existing in three isoforms. Two of them, endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS), collectively called as constitutive nitric oxide synthase (cNOS), are responsible for continuous basal release of NO and both, require calcium/calmodulin for activation. The other one is called as inducible nitric oxide synthase (iNOS), is responsible for prolonged release of NO and does not require calcium/calmodulin for activation. It is expressed in response to inflammatory cytokines and lipopolysaccharides. Low concentration of NO increased the motility and viability of spermatozoa. However, high concentration of NO decreased the sperm motility and viability. The bimodal motility response to various concentrations of NO releasing compounds could be due to dual nature of NO, as both a transduction molecule at low concentration and a cytotoxic effector at high concentrations in systems. NO inhibits cellular respiration by nitrosylation of heme in mitochondrial enzymes, aconitase and glyceraldehyde-3-phosphate dehydrogenase, leading to a depletion of ATP and consequent loss of motility in the spermatozoa. The primary mechanism of NO induced sperm damage is likely to be the inhibition of mitochondrial respiration and DNA synthesis. NO induced toxicity is also mediated indirectly through its interaction with superoxide anions and formation of