Antisperm Antibodies and Sperm Membrane Potential in Diabetes Mellitus: New Insights on Its Role in Male Infertility

Abstract

Diabetes mellitus is a chronic metabolic condition that is increasingly been recognised as a potential factor to decreased male reproductive function. Erectile dysfunction and hypogonadism are well established reproductive complications of diabetes, but an increasing body of evidence suggests that hyperglycaemia, oxidative stress, advanced glycation end products, chronic inflammation, mitochondrial dysfunction and disruption of the blood-testis barrier may directly impair spermatogenesis and sperm function. Among the biological repercussions of these disturbances, the modification of the integrity and the membrane potential of the spermatozoa membrane is of special importance as sperm membrane potential is involved in capacitation, ion homeostasis, motility, calcium signalling and the acrosome reaction. Oxidative stress from diabetes may change membrane lipids, ion channels and mitochondrial function, which could affect the electrical and metabolic properties necessary for optimal sperm function. Simultaneously, the rupture of blood–testis or blood–epididymal barriers may result in the exposure of normally shielded sperm antigens to the immune system and the formation of antisperm antibodies. Antisperm antibodies can attach to sperm surface antigens and interfere with sperm motility, sperm capacitation, cervical mucus penetration, sperm-zona pellucida interaction and fertilisation. But direct evidence for a molecular relationship between diabetes, antisperm antibody production and sperm membrane potential is still lacking. This review describes the biological basis of sperm membrane potential, and the effects of diabetes on sperm membrane potential and mitochondrial function, and the immunological basis of antisperm antibody formation and the possible interactions between metabolic and immunological mechanisms in diabetic male infertility. The research suggests that antisperm antibodies and sperm membrane potential may be complimentary indicators for various but related aspects of diabetic reproductive failure. Future studies should examine simultaneously glycaemic control, antisperm antibodies, sperm plasma-membrane potential, mitochondrial membrane potential, oxidative stress and conventional semen parameters to determine if these biomarkers provide additional information about fertility impairment in men with diabetes.