Skip to main content
Download PDF

How much obesity and diabetes do impair male fertility?

Reproductive Biology and Endocrinology volume 21, Article number: 48 (2023) Cite this article

Abstract

Background

Subfertility in obese and diabetic men during the reproductive age is evident, but the mechanisms by which obesity and diabetes mellitus cause male infertility are not entirely understood. The current study aimed to evaluate the effects and potential mechanisms of obesity and diabetes on male fertility.

Methods

We enrolled control = 40, obese = 40, Lean-DM = 35, and Obese-DM = 35 individuals. The obesity-associated markers, diabetic markers, hormonal and lipid profile, inflammatory indices, and semen analysis were assessed in four experimental groups.

Results

Our finding showed that diabetic markers were significantly increased in two diabetic groups, while obesity indices were markedly increased in two obese groups. Conventional sperm parameters were significantly lower in three groups compared with the control. Serum levels of total testosterone and sex hormone-binding globulin were significantly lower in men with obesity and DM compared with the control. There was a significant difference in the concentration of high-sensitivity C-reactive protein among four experimental groups. Moreover, serum leptin was significantly increased in obese DM, lean DM, and obese groups. Serum insulin levels had a positive correlation with metabolic-associated indices and high-sensitivity C-reactive protein levels, whereas it had a negative correlation with count, motility, and morphology.

Conclusions

Our findings showed the metabolic changes, hormonal dysfunction and inflammatory disturbance might be suspected mechanisms of subfertility in obese and diabetic subfertile men.

Background

Obesity and type 2 diabetes mellitus (DM) are two known metabolic disorders with an increasing prevalence and high mortality rate [1]. Metabolic disorders are characterized by hyperglycemia, hyperlipidemia, and insulin resistance, increasing the risk of cardiovascular diseases and premature death [2]. Approximately half of the patients with type 2 diabetes are obese. The increasing incidence of diabetes can thus be attributed to the global epidemic of obesity.

Alongside an increased incidence in diabetes and obesity, infertility is a growing concern affecting up to 15% of couples trying to conceive globally. Recently, the effects of obesity and diabetes on fertility have been extensively investigated [2,3,4]. Although reproductive dysfunction and declined quality of semen were reported in obesity and diabetes [5], but There is are no clear studies of the involved molecular signaling pathways in obese and diabetic-related infertility complications and the mechanisms by which obesity and diabetes mellitus (DM) causes male infertility are not clearly explained [6,7,8].

Multiple pathways have been proposed for the decline in male fertility in obese and diabetes men. These histopathological changes could be the result of impaired Hypothalamus Pituitary Gonadal (HPG) Axis [9,10,11], increased reactive oxygen species (ROS) and DNA fragmentation of spermatozoa [12, 13], biochemical disturbance [14, 15], Several lines of evidence have shown the role of hormonal and antioxidant in sub fertility following diabetes and obesity [16]. Besides, the role of inflammatory markers in the development of diabetes mellitus and obesity have been addressed [17] [18]. This study aimed to determine the impact of obesity and diabetes, alone or combined that may affect male reproductive functions.

Materials and methods

Data collection

In this case–control study, 150 subjects with the age range of 30–50 years old were selected from the Royan Institute Infertility Center (a referral infertility clinic in Tehran, Iran) They were divided into the following groups:

  1. 1-

    Control group: consisted of men with normal weight who were non-diabetic

  2. 2-

    Lean DM group: included men with normal weight who were afflicted with diabetes

  3. 3-

    Obese group: comprised of obese men who were non-diabetic

  4. 4-

    Obese-DM group: consisted of obese men who were affected by diabetes mellitus

The experimental procedure of the current research was approved by the Ethics Committee of Royan Institute (No. IR.ACECR.ROYAN.REC.1396.53). Informed consent was obtained from all individuals who voluntarily participated in our study. The questionnaire was completed for each participant, including demographic characteristics, medical and drug histories, smoking status, alcohol consumption, sexual activity, and surgical history. Males with a history of azoospermia, urogenital infections, varicocele, chronic severe debilitating medical illness (cerebrovascular, cardiovascular, sexually transmitted diseases, systemic disorders, and acute infections) were excluded from the study.

Anthropometrical measure

After enrollment, all participants underwent physical examinations that included anthropometric measurements [body height and weight, waist circumference (WC), and hip circumference (HC)]. The body mass index (BMI) was classified into normal weight (BMI 18–25 kg/m2) and obese (BMI ≥ 30 kg/m2). Waist circumference, hip circumference, and the waist to hip ratio (WHR) were also measured. Diabetes mellitus was diagnosed according to the diagnostic criteria provided by the American Diabetes Association [19].

Body height and weight were determined for each participant standing without shoes and heavy outer garments. Waist circumference was calculated at the level midway between the lower rib margin and the iliac crest of participants in a standing position without heavy outer garments and with emptied pockets, breathing out gently. Hip circumference was recorded as the maximum circumference over the buttocks. The BMI was evaluated by dividing the body weight (in kilograms) by height (in meters) squared (kg/m2). The waist to hip ratio (WHR) was calculated as the ratio of waist circumference over the hip circumference. WHR was calculated as the ratio of waist circumference over the height.

Semen analysis

Semen samples were obtained after 2–5 days of sexual abstinence and allowed to liquefy for 30 min at 37°. When semen liquefaction was completed, sperm progressive motility, sperm morphology, and semen volume were measured according to the guideline established by WHO in 2010. The CASA system [SPERM CLASS ANALYZER software (SCATM, Microptic, Version 4.2, Barcelona, Spain)] was applied to assess sperm progression, overall motility, and sperm concentration. Spermatozoa were classified as progressive motile (WHO class A + B), non-progressive motile (class C), and immotile (class D). Papanicolaou staining was employed for the analysis of sperm morphology.

Clinical and biochemical assessment

Biochemical markers, such as serum glucose concentrations were measured using a standard enzymatic method (Roche Diagnostics GmbH, Mannheim, Germany). Serum insulin level was determined using the Electro-chemiluminescence immunoassay (ECLIA) kit (Roche Diagnostics GmbH, Mannheim, Germany). Glycosylated hemoglobin (HbA1C (was analyzed by the Nyco Card Reader II analyzer according to the manufacturer's instructions. Homeostasis model assessment of insulin resistance (HOMA-IR) was assessed according to the following formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Serum triglyceride (TG), cholesterol, and high-density lipoprotein (HDL) levels were evaluated by enzymatic methods (Biorex). Serum concentrations of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were determined.

Reproductive hormones

After overnight fasting, 10 ml of peripheral blood was taken by a trained nurse between 8:00 and 10:00 AM. Serum samples were separated by centrifugation at 3000 g for 15 min, and stored at -80 °C until usage. The concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured using commercial ELISA kits (Pishtaz Teb Inc., Tehran, Iran). The levels of Total Testosterone (TT) and Serum-free testosterone (FT) were assessed by a commercial ELISA kit (AccuBind ELISA Microwells, Monobina Inc., Lake Forest, CA, USA). Sex hormone-binding globulin (SHBG) levels were analyzed by the electro-chemiluminescence immunoassay (ECLIA) kit.

Determination of serum pro-inflammatory cytokines

Serum leptin was analyzed by the Human Leptin ELISA Kit (RayBiotech, Inc., Norcross, Georgia, USA). Proinflammatory cytokines, including IL-1, IL-6, and TNF-α were quantified using commercial ELISA kits (RayBiotech, Inc., Norcross, Georgia, USA) according to the manufacturer’s instructions. High-sensitivity C-reactive protein (hs-CRP) levels were evaluated using the CRP kit (pars Azmoon Kit, Tehran, Iran).

Statistical analyses

Data were presented as the means and standard error of the mean (mean ± SEM). All statistical analyses were performed by the SPSS software (version 16; SPSS, Chicago, ILL). The Kolmogorov–Smirnov test was utilized to examine whether the data were normally distributed. In the case of normal distribution One-way analysis of variance (ANOVA) was applied followed by DunnettT3 post hoc test); otherwise, the Kruskal–Wallis test was employed followed by Bonferroni Correction post hoc test. The correlations among lipids profiles, sperm parameters, and inflammatory factors were calculated by Pearson's correlation coefficient test. The p-value.

of less than 0.05 was considered statistically significant.

Results

A total of 150 men entered to this study. The subjects were classified into four groups based on obesity and diabetes status (40 men with normal weight who were non-diabetic as controls, 35 men with normal weight who were afflicted with diabetes as lean DM group, 40 obese men who were non-diabetic as obese group, and 40 obese men who were affected by diabetes mellitus as obese-DM group). Table 1 presents the results regarding comparison of clinical parameters among these four groups. The four groups were comparable regarding age, BMI, waist and hip circumference. Statistically higher mean age was observed in lean and obese DM groups compared to obese and control groups (p = 0.001).

Table 1 Clinical and biochemical parameters of the study population
Full size table

Figure. 1 presents the results regarding comparison of biochemical parameters among these four groups. The four groups were comparable regarding, FBS, HbA1C, HOMA-IR, serum insulin, serum leptin, triglyceride, HDL-cholesterol, and VLDL. There is a significant change in serum insulin between obese and diabetic obese, groups and lean DM and control groups (p = 0.02 and p = 0.001, respectively; ANOVA followed by Tukey's post hoc test). There was a significant difference observed in serum leptin between obese and diabetic obese groups, and lean DM and control groups (p = 0.001, and p = 0.016, respectively; ANOVA followed by Tukey's pos hoc test). There were higher mean Triglyceride levels in diabetic obese men compared with control group (p = 0.004). In contrast, there were lower mean HDL-cholesterol levels in diabetic obese men compared with control group (p = 0.021) (Fig. 2).

Fig. 1
figure 1

FBS: fasting blood sugar; HbA1C: glycosylated hemoglobin; HOMA-IR homeostasis model assessment of insulin resistance. *Obtained by One-way analysis of variance (ANOVA) test at significant level of 0.05

Full size image
Fig. 2
figure 2

HDL: high-density lipoprotein; LDL: low-density lipoprotein. VLDL: Very low-density lipoprotein. *Obtained by One-way analysis of variance (ANOVA) test at significant level of 0.05

Full size image

Hormones and semen parameters

Sperm parameters and hormone concentrations were depicted in Table 2. There was a significant difference among these four groups by sperm parameters. Post hoc Tukey simultaneous tests indicated that sperm motility, progressive motility, sperm count, and sperm morphology were significantly lower in obese-DM (p = 0.001), lean DM (p = 0.01), and obese groups (p = 0.001) compared with the control group. No significant difference was found in hormone concentrations except for SHBG. Post hoc Tukey simultaneous tests revealed that the control group had statistically significantly higher mean SHBG than obese-DM (p = 0.001) and obese groups (p = 0.011).

Table 2 The comparison of sperm parameters and hormone concentrations among four experimental groups
Full size table

Pro-inflammatory cytokines

The comparison of pro-inflammatory cytokines among four groups is shown in Fig. 3. There was a marked difference in the concentration of hs-CRP when all of the four groups were compared, the highest level of hs-CRP were assessed in obese DM. There was a significant difference between obese and diabetic obese groups, and control groups (p = 0.000, and p = 0.014, respectively; ANOVA followed by Tukey's pos hoc test). Moreover, serum leptin, which is considered an adipokine was significantly higher in obese-DM, lean DM, and obese groups in comparison with the control group. There was a significant difference between obese and diabetic obese groups, and lean DM and control groups (p = 0.000, and p = 0.016, respectively; ANOVA followed by Tukey's pos hoc test) Fig. 1.

Fig. 3
figure 3

The comparison of hs-CRP, interleukin (IL)-1, IL-6 and TNF-α levels among all experimental groups. Hs-CRP: high-sensitivity C-reactive protein; IL-6, interleukin-6; IL-1: interleukin-1; TNF- α: tumor necrosis factor-alpha. Uppercase letters vs. the same lowercase letters (A vs. a, B vs. b, and C vs. c) indicate a statistically significant difference (p < 0.05)

Full size image

Discussion

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.

Conclusion

The results of this study indicated the association of metabolic changes and hormonal dysfunction. Our findings showed that the obese and diabetic men with higher inflammatory parameters had met worse basic sperm parameters compared to controls. Inflammatory markers may be possible diagnostic value in male infertility adding to other mechanisms. It seems that obesity and diabetes negatively affect the male reproductive organ through the detrimental changes in all three mechanisms mentioned earlier, which warrants further studies.

Availability of data and materials

Please contact author for data requests.

Abbreviations

DM:

Type 2 diabetes mellitus

HPG:

Hypothalamus Pituitary Gonadal

ROS:

Reactive oxygen species

WC:

Waist circumference

HC:

Hip circumference

BMI:

Body mass index

WHR:

Waist to hip ratio

WHO:

World Health Organization

HbA1C:

Hemoglobin A1c

HOMR-IR:

Homeostatic Model Assessment for Insulin Resistance

TG:

Serum triglyceride

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

VLDL:

Very low-density lipoprotein

LH:

Luteinizing hormone

FSH:

Follicle-stimulating hormone

TT:

Total Testosterone

FT:

Serum-free testosterone

SHBG:

Sex hormone-binding globulin

SPSS:

Statistical Package for Social ScienceS

References

  1. DeFronzo, R.A. and E. Ferrannini, Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care, 1991. 14(3): p. 173–94.

  2. Ventimiglia E, et al. Metabolic syndrome in White-European men presenting for secondary couple’s infertility: an investigation of the clinical and reproductive burden. Asian J Androl. 2017;19(3):368–73.

    Article  CAS  PubMed  Google Scholar 

  3. Ehala-Aleksejev K, Punab M. The effect of metabolic syndrome on male reproductive health: A cross-sectional study in a group of fertile men and male partners of infertile couples. PLoS ONE. 2018;13(3):e0194395.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Guariguata L, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–49.

    Article  CAS  PubMed  Google Scholar 

  5. Bashah, N.A.K. and M.M. Noor, ANTIHYPERGLYCEMIC AND ANDROGENIC PROPERTIES OF Moringa oleifera LEAVES AQUEOUS EXTRACT ATTENUATE SEXUAL DYSFUNCTION IN DIABETES-INDUCED MALE RATS.

  6. Cabler S, et al. Obesity: modern man’s fertility nemesis. Asian J Androl. 2010;12(4):480–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Condorelli RA, et al. Diabetes Mellitus and Infertility: Different Pathophysiological Effects in Type 1 and Type 2 on Sperm Function. Front Endocrinol (Lausanne). 2018;9:268.

    Article  PubMed  Google Scholar 

  8. Katib A. Mechanisms linking obesity to male infertility. Cent European J Urol. 2015;68(1):79–85.

    PubMed  PubMed Central  Google Scholar 

  9. Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab. 2011;96(8):2341–53.

    Article  CAS  PubMed  Google Scholar 

  10. Dandona P, Dhindsa S. Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9):2643–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kerr JB, et al. Stage-dependent changes in spermatogenesis and Sertoli cells in relation to the onset of spermatogenic failure following withdrawal of testosterone. Anat Rec. 1993;235(4):547–59.

    Article  CAS  PubMed  Google Scholar 

  12. Zorn B, Vidmar G, Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl. 2003;26(5):279–85.

    Article  CAS  PubMed  Google Scholar 

  13. Abbasihormozi SH, et al. Stress Hormone and Oxidative Stress Biomarkers Link Obesity and Diabetes with Reduced Fertility Potential. Cell J. 2019;21(3):307–13.

    PubMed  PubMed Central  Google Scholar 

  14. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–9.

    Article  PubMed  Google Scholar 

  15. Lu JC, et al. Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men. PLoS ONE. 2016;11(1):e0146304.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Di Domenico M, et al. The Role of Oxidative Stress and Hormones in Controlling Obesity. Front Endocrinol (Lausanne). 2019;10:540.

    Article  PubMed  Google Scholar 

  17. Fan W, et al. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility. Front Physiol. 2017;8:1117.

    Article  PubMed  Google Scholar 

  18. Azenabor A, Ekun AO, Akinloye O. Impact of Inflammation on Male Reproductive Tract. J Reprod Infertil. 2015;16(3):123–9.

    PubMed  PubMed Central  Google Scholar 

  19. Targets G. <em>Standards of Medical Care in Diabetes—2018</em>. Diabetes Care. 2018;41(Supplement 1):S55–64.

    Google Scholar 

  20. Palmer NO, et al. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012;2(4):253–63.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Temidayo S, Stefan S. Diabetes mellitus and male infertility. Asian Pacific Journal of Reproduction. 2018;7(1):6–14.

    Article  Google Scholar 

  22. Alves MG, et al. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function. Tissue Barriers. 2013;1(2):e23992.

    Article  PubMed  PubMed Central  Google Scholar 

  23. La Vignera S, et al. High levels of lipid peroxidation in semen of diabetic patients. Andrologia. 2012;44(Suppl 1):565–70.

    Article  PubMed  Google Scholar 

  24. Sermondade N, et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update. 2013;19(3):221–31.

    Article  CAS  PubMed  Google Scholar 

  25. Eisenberg ML, et al. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod. 2014;29(2):193–200.

    Article  PubMed  Google Scholar 

  26. Bakar UA, Subramaniam P, Bashah NAK, Kamalrudin A, Kamaruzaman KA, Jasamai M, et al. Sperm Proteomics Analysis of Diabetic Induced Male Rats as Influenced by Ficus carica Leaf Extract. 2020.

  27. Al Hayek AA, et al. Assessment of Hypogonadism in Men With Type 2 Diabetes: A Cross-Sectional Study From Saudi Arabia. Clin Med Insights Endocrinol Diabetes. 2017;10:1179551417710209.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pivonello R, et al. Metabolic Disorders and Male Hypogonadotropic Hypogonadism. Front Endocrinol (Lausanne). 2019;10:345.

    Article  PubMed  Google Scholar 

  29. Anderson SG, et al. Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort. Prim Care Diabetes. 2012;6(2):143–8.

    Article  PubMed  Google Scholar 

  30. Biswas M, et al. Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes-related quality of life. Clin Endocrinol (Oxf). 2012;76(5):665–73.

    Article  CAS  PubMed  Google Scholar 

  31. Corona G, et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res. 2006;18(2):190–7.

    Article  CAS  PubMed  Google Scholar 

  32. Ogbera AO. Relationship between serum testosterone levels and features of the metabolic syndrome defining criteria in patients with type 2 diabetes mellitus. West Afr J Med. 2011;30(4):277–81.

    CAS  PubMed  Google Scholar 

  33. Allan CA, et al. The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men. Med J Aust. 2006;185(8):424–7.

    Article  PubMed  Google Scholar 

  34. Cooper LA, et al. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing–implications for the interpretation of total testosterone measurements. Clin Endocrinol (Oxf). 2015;83(6):828–33.

    Article  CAS  PubMed  Google Scholar 

  35. Lee HK, Lee JK, Cho B. The role of androgen in the adipose tissue of males. World J Mens Health. 2013;31(2):136–40.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Michalakis K, et al. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism. 2013;62(4):457–78.

    Article  CAS  PubMed  Google Scholar 

  37. Jensen TK, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82(4):863–70.

    Article  CAS  PubMed  Google Scholar 

  38. Mohanraj L, et al. IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of atherosclerosis. PLoS ONE. 2013;8(1):e55084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Daniele G, et al. The inflammatory status score including IL-6, TNF-alpha, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol. 2014;51(1):123–31.

    Article  CAS  PubMed  Google Scholar 

  40. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363–74.

    Article  CAS  PubMed  Google Scholar 

  41. Zhou X, You S. Rosiglitazone inhibits hepatic insulin resistance induced by chronic pancreatitis and IKK-beta/NF-kappaB expression in liver. Pancreas. 2014;43(8):1291–8.

    Article  CAS  PubMed  Google Scholar 

  42. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–6.

    Article  CAS  PubMed  Google Scholar 

  43. de Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett. 2008;582(1):97–105.

    Article  PubMed  Google Scholar 

  44. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1–2):20–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415–45.

    Article  CAS  PubMed  Google Scholar 

  46. Emanuela F, et al. Inflammation as a Link between Obesity and Metabolic Syndrome. J Nutr Metab. 2012;2012:476380.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Harris RB. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta. 2014;1842(3):414–23.

    Article  CAS  PubMed  Google Scholar 

  48. Caron A, et al. Leptin and brain-adipose crosstalks. Nat Rev Neurosci. 2018;19(3):153–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Odle AK, et al. Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence. Front Endocrinol (Lausanne). 2017;8:367.

    Article  PubMed  Google Scholar 

  50. Martins AD, Majzoub A, Agawal A. Metabolic Syndrome and Male Fertility. World J Mens Health. 2019;37(2):113–27.

    Article  PubMed  Google Scholar 

  51. Hasan H, et al. Mechanism of Inflammatory Associated Impairment of Sperm Function Spermatogenesis and Steroidogenesis. Front Endocrinol (Lausanne). 2022;13:897029.

    Article  PubMed  Google Scholar 

  52. Wdowiak A, et al. Chronic Inflammation Impairs Male Fertility—A Case-Control Study in Ulcerative Colitis Patients. J Clin Med. 2021;10:1460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jiang L, et al. Association of semen cytokines with reactive oxygen species and histone transition abnormalities. J Assist Reprod Genet. 2016;33(9):1239–46.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Havrylyuk A, et al. Cytokines in the blood and semen of infertile patients. Cent Eur J Immunol. 2015;40(3):337–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the clinicians, clinical embryologists, Andrology and Epidemiology and Dr. Zahednasab for the proof-reading and edition of the manuscript.

Funding

This study was financially supported by Royan Institute. for Reproductive Biomedicine, ACECR, Tehran, Iran.

Author information

Authors and Affiliations

  1. Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, P.O. Box: 16635-148, Iran

    Shima AbbasiHormozi, Azam Kouhkan, Abdolhossein Shahverdi & Samira Vesali

  2. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Shima AbbasiHormozi & Abdolhossein Shahverdi

  3. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Amir Parikar

  4. Faculty of Sport Science & Health, Shahid Beheshti University, Tehran, Iran

    Azin Shirin

Authors
  1. Shima AbbasiHormozi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azam Kouhkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdolhossein Shahverdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amir Parikar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Azin Shirin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Samira Vesali
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Azam Kouhkan M.D and Abdolhossein Shahverdi Ph.D. (conception and design of the study, final approval of the version to be published), Samira Vesali (analysis and interpretation of data), Amir parhizkar (questioner)and Shima Abbasihormozi Ph.D (conception and design of the study,collection of data, drafting the article.

Corresponding author

Correspondence to Azam Kouhkan.

Ethics declarations

Ethics approval and consent to participate

Ethics approval and consent to participate Ethical approval number: IR.ACECR.ROYAN.REC.1396.53.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

AbbasiHormozi, S., Kouhkan, A., Shahverdi, A. et al. How much obesity and diabetes do impair male fertility?. Reprod Biol Endocrinol 21, 48 (2023). https://doi.org/10.1186/s12958-022-01034-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12958-022-01034-w

Keywords

Reproductive Biology and Endocrinology

ISSN: 1477-7827

Contact us