Abstract
Although the prevalence of sub-infertility in diabetic patients in childbearing age is known, the mechanisms by which diabetes mellitus (DM) causes male infertility are not completely explained. This detrimental effect is achieved with a variety of mechanisms that include pre-testicular, testicular, and post-testicular pathogenetic moments and can be different in type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) patients because of type of diabetes, duration of disease, and glycemic metabolic compensation. Aim of this study was to evaluate whether diabetic disease can be considered a risk factor for infertility considering the etiopathogenetic differences between DM1 and DM2 on sperm function. We enrolled 38 DM1 patients and 55 DM2 patients with idiopathic infertility history >12 months, and 100 healthy fertile subjects. The following outcomes were evaluated in optical microscopy and flow cytometry: sperm function (by conventional and biofunctional sperm parameters) and signs of urogenital infection/inflammation (by sperm leukocyte concentrations and indices of oxidative stress). Moreover, an andrological evaluation (by didymo-epididymal ultrasound evaluation, serum total testosterone, LH, and FSH measurements) was performed in DM1 and DM2 patients compared to controls. Diabetic patients showed a higher risk of becoming infertile and the pathophysiological mechanisms of damage were different in DM1 and DM2. Conventional sperm parameters of diabetic patients are worse than controls (p < 0.05). The DM2 caused an inflammatory condition with increased oxidative stress resulting in decreased sperm vitality and increased sperm DNA fragmentation. DM1 altered epididymal voiding causing low ejaculate volume and mitochondrial damage resulting in decreased sperm motility. These findings and evidences support the contention that DM could be regarded as cause of male infertility suggesting that the prevention of diabetic disease in DM2 and the follow-up of seminal parameters in DM1 could prevent fertility decline in these categories of patients.
Highlights
An increased number of male patients with diabetes mellitus (DM) have been reported in childbearing age and the DM prevalence is closely associated with the decline of fertility [1, 2]
Progressive motility was lower in patients with DM1 and DM2 compared to controls (p < 0.05), and it was lower in DM1 than in DM2 patients (p < 0.05)
Seminal fluid volume was significantly lower in patients with DM1 (p < 0.05), while it did not seem to undergo significant changes in DM2 patients compared to controls
Summary
An increased number of male patients with diabetes mellitus (DM) have been reported in childbearing age and the DM prevalence is closely associated with the decline of fertility [1, 2]. The early course of DM2 in young people could be more disruptive leading to poor quality of life as well as in DM1 patients: evidences suggest that loss of β-cell function is accelerated in young-onset DM2 and prevalence estimates show a 31% increase already in DM2 among people aged 10–19 years [4]. These epidemiological data suggest that the diabetic disease arrives even before the desire to have a child. DM1 is able to influence the expression of genes involved in sperm DNA repair, resulting in a high rate of nuclear DNA fragmentation [7], mitochondrial DNA deletions [5, 6, 8, 9] with mitochondrial respiratory chain alteration and subsequent decreased sperm motility [10]
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