The discovery of mitochondrial derive
peptides (MDPs) has spotlighted mitochondria as central hubs in control and regulation of cell viability and metabolism in the testis in response to intracellular and extracellular stresses. MDPs (
Humanin, MOTS-c and SHLP-2) are present in testes.
Humanin, the first MDP, is predominantly expressed in Leydig cells, and moderately in germ cells and seminal plasma. The administration of synthetic
humanin peptide agonist HNG protects male germ cells against apoptosis induced by intratesticular hormonal deprivation, testicular
hyperthermia, and chemotherapeutic agents in rodent testes.
Humanin interacting with
IGFBP-3 and/or Bax (
pro-apoptotic proteins) prevents the activation of germ cell apoptosis.
Humanin participates in the network of
IL-12/IL-27 family of
cytokines to exert the immune-modulation of the testicular environment.
Humanin and other MDPs may be important in the amelioration of testicular stress and prevention of cell injury with possible implications for
male infertility, fertility preservation and
contraceptive development.