Diabetes-induced male infertility: potential mechanisms and treatment options

Abstract

Male infertility is a physiological phenomenon in which a man is unable to impregnate a fertile woman during a 12-month period of continuous, unprotected sexual intercourse. A growing body of clinical and epidemiological evidence indicates that the increasing incidence of male reproductive problems, especially infertility, shows a very similar trend to the incidence of diabetes within the same age range. In addition, a large number of previous in vivo and in vitro experiments have also suggested that the complex pathophysiological changes caused by diabetes may induce male infertility in multiple aspects, including hypothalamic-pituitary-gonadal axis dysfunction, spermatogenesis and maturation disorders, testicular interstitial cell damage erectile dysfunction. Based on the above related mechanisms, a large number of studies have focused on the potential therapeutic association between diabetes progression and infertility in patients with diabetes and infertility, providing important clues for the treatment of this population. In this paper, we summarized the research results of the effects of diabetes on male reproductive function in recent 5 years, elaborated the potential pathophysiological mechanisms of male infertility induced by diabetes, and reviewed and prospected the therapeutic measures.

Keywords: Chronic inflammation; Diabetes; Endocrine disorders; Hyperglycemia; Male infertility; Oxidative stress; Sperm.

Fig. 1

Diabetic comorbidities: Complex pathophysiological changes. AGEs: advanced glycation end products; NEFA: nonestesterified fatty acid; UPR: unfolded protein response; ROS: reactive oxygen species; RNS: reactive nitrogen species; HG: high glucose; TNF: tumor necrosis factor; PKC: Protein kinase C; MAPK: Mitogen-activated protein kinase; CAT: catalase; SOD: superoxide dismutase; GSH: glutathione

Fig. 2

Potential mechanism of diabetes-induced male infertility. HG: high glucose; ROS: reactive oxygen species; UPR: unfolded protein response; MMP: mitochondrial membrane potential; CHOP: C/EBP homologous protein; AGEs: advanced glycation end products; RAGE: the receptor of advanced glycation endproducts; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PI₃: phosphoinositide 3; mTOR: mammalian target of rapamycin; p70S6K: p70 ribosomal protein S6 kinase; Nrf2: Nuclear factor erythroid 2-related factor 2; ED: erectile dysfunction; HPG: hypothalamic-pituitary–gonadal axis; GnRH: Gonadotropin-Releasing Hormone; FSH: follicle-stimulating hormone; LH: luteinizing hormone; AP-1: activator protein 1; ET-1: endothelin-1; ICR: imprinting control area