The role of nitric oxide in the development of diseases of the male reproductive system and its potential applications in clinical practice

Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological and pathological importance. Physiological mechanisms mediated by NO mainly include angiogenesis, growth, puberty, and senescence. NO has vital roles in normal reproduction, including steroidogenesis, gametogenesis, and the regulation of germ-cell apoptosis. In males, NO is a key player in steroidogenesis, erectile functions, sperm capacitation, and acrosome reaction. Moreover, NO is also a regulator of Sertoli cell-germ cell interaction and maintenance of the blood-testis barrier. In pathological conditions such as infections, increased nitric oxide synthase activities stimulate the excessive synthesis of NO which acts as a proinflammatory mediator inducing oxidative stress, detrimental to reproductive functions in males. Excessive NO synthesis disrupts gonadal functions and induces germ cell apoptosis and oxidative damage to the germ cells. This review elucidates how the differences in NO expression levels account for its beneficial and adverse impacts on male fertility.