How much obesity and diabetes do impair male fertility?

Accumulative evidence shows the association of male reproductive dysfunction with the development of obesity and diabetes [8, 20, 21].Hyperinsulinemia and hyperglycemia are common metabolic disorders usually detected in obese and diabetic men, having adverse effects on sperm quantity and quality [22]. Previous investigations reported that obesity and diabetes were associated with reproductive health problem and sub fertility [23, 24]. The results achieved in this study showed that disturbances in sperm parameters in men were probably due to overweight and overall obesity and diabetes.

Our finding indicated the increased levels of serum FBS, HbA1c, insulin, and insulin resistance, as well as older age, in diabetic men. Also, two obese groups had higher BMI and waist circumference values compared with other groups. The values of WHR, serum triglyceride, and VLDL were substantially lower in the control group when compared with other experimental groups. Also, obese DM group had higher levels of triglyceride and VLDL than lean DM and obese groups.

Similar to our results, some studies reported higher values of BMI, waist circumference in diabetic patients in comparison with healthy subjects. Diabetes mellitus has been linked with the lower semen parameters, including total sperm count, normal sperm morphology, sperm motility, and sperm progression [25, 26]. It seems that secondary hypogonadism occurs in obese and diabetic population [10, 27, 28], thus it is not surprising that in present study The present study showed the highest levels of serum testosterone and SHBG in the control group. Previously, higher prevalence of hypogonadism has been reported in patients with type 2 diabetes mellitus, ranging from 4 to 45% [29,30,31,32], along with obese individuals, ranging from 15 to 78% [33]. Serum testosterone in obesity and diabetes is commonly associated with the development of secondary hypogonadism [10]. The lower levels of testosterone and SHBG are linked with obesity and higher values of BMI [34]. As a putative mechanism, Aromatization of testosterone occurs in the adipose tissue, deriving the peripheral conversion of testosterone into estradiol [35].

Most of studies have primarily focused on the correlation of increased BMI, adiposity [15], and endocrine dysfunction with the semen quality [6, 36, 37]. Thus, both biochemical and hormonal mechanisms contribute to sperm damages in diabetic and obese men.

We assessed inflammatory biomarkers as another possible mechanism. Our data demonstrated that hs-CRP levels were significantly higher in obese, obese DM and lean DM than controls. Besides, the obese DM group had significantly higher levels of insulin and insulin resistance in comparison with other groups. It seems that adiposity and hyperglycemia alone or in combination are critical factors in the increase of the levels of insulin, insulin resistance, and acute inflammatory biomarkers [38,39,40].

The current study showed that the serum concentration of IL-1β was significantly increased in lean DM and obese groups compared with the control and obese DM groups; however, there were no significant differences in serum concentrations of IL-6 and TNF-α among four experimental groups. In agreement with other studies, we found that obesity, hyperglycemia, and metabolic disturbance may be associated with the alternation of inflammatory pathways and reproductive health problem [41,42,43].

The present data demonstrated a positive correlation of metabolic factors, including FBS, HbA1c, insulin resistance, waist circumference, and BMI with serum hs-CRP, leptin levels, and the semen parameters. It appears that obesity could modify inflammatory biomarkers and immune system activity [17, 44,45,46] directly or indirectly, in addition, the inflammatory factors, such as hs-CRP and leptin may lead to the altered metabolic indices. Adipocytes are responsible for the production of leptin [47, 48]. Higher levels of serum leptin were observed in two obese groups and this hormone per se influences the secretion of LH and FSH from the pituitary, leading to changes in the amplitude of the released pulses, as well as the pulsatility. Therefore Inflammation can harm affects the balance of the HPG axis as a result of presence extra adipose tissue [49]. Finally, metabolic alternations may affect reproductive health and the semen parameters [3, 50] In an experimental study conducted by Fan et al. concluded that the chronic inflammatory status leads to the impairment of the reproductive system in obese [17, 51].

Recently, Condorelli and colleagues investigated several pathophysiological factors on the sperm function in men with type 1 and type 2 diabetes. They suggested the involvement of two main putative mechanisms, including an inflammatory condition accompanied by increased oxidative stress and sperm DNA fragmentation in type 2 diabetes mellitus, along with mitochondrial damages in type 1 diabetes [7, 52].

The present study assessed the association of three mechanisms (hormonal, biochemical and inflammatory) with male sub fertility [7]. Nevertheless, the current research had several limitations, such as lack of the assessment of other pro inflammatory markers. Besides, the present study assessed pro inflammatory cytokines only in blood samples and It is recommended that inflammatory biomarkers be examined in other tissues [53, 54], which shed more light on inflammatory and male infertility.

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