Impairment of fertility is a great problem of couples nowadays. It is estimated that even 15% of people in the reproductive age in the developed countries may be infertile (1). Epidemiological and clinical data show that every seventh couple in the Western world is infertile currently, and in 40% it results from a “problem” of the man (2). For example, it has been shown in the USA that fertility rates (births per 1000 men) decreased from 57.0 in 1980 to 45.8 in 2013 (3). Similar data comes from Europe. It was found in Denmark that the number of newborns per man at the 45 years of age declined in years 1990-2005 from 1.9 to 1.7 (4).

Sub- or total infertility is a result of several genetic and non-genetic factors. As it has been observed in the numerous cohort studies, one of the more important among these factors is obesity. Data from The Danish National Birth Cohort Study, published in the 2007 year obtained on the basis of the analysis of 47 835 pairs showed that the time to pregnancy (TTP) over 12 months happens much more often when the men has a body mass index (BMI) over 30 kg/m² compared to men without obesity: AOR (adjusted odds ratio) for obesity in men is 1.53 (95% CI 1.32-1.77). If excessive weight occurs either in female the AOR rises to 2.75 (95% CI 2.27-3.30) (5). Also The Norwegian Mother and Child Cohort Study, involving 26 303 couples has shown that TTP longer than 12 months is observed more often when a man is overweight (BMI > 27 kg/m²). AOR in such situation is 1.20 (1.04-1.38). When a man’s BMI rises above 30 kg/m² AOR increases to 1.36 (1.13-1.63) (6). The impact of obesity on fertility must be therefore regarded as an important social problem, especially when it is well known that since 1980 the number of obese people all over the world has doubled and now 65% of people live in countries in which excessive body weight is a larger health problem than malnutrition. It is calculated that the health costs of obesity in developed countries reaches approximately £ 2 billion per year (7). Concomitantly, in the last 50 years a continuous decline in fertility has been observed, parallel to the growth of the degree of obesity (8). Male infertility is largely associated with the deterioration of the semen quality. A direct correlation between BMI and a decline in the number and motility of sperm was proved (9). Already overweight, and to a greater extent obesity increase the risk of damage of germ cell’s DNA (10). Moreover, it is well known that excessive body weight affects the sexual possibilities. Erectile dysfunction of a various degree have been found nearly in 96% of the 256 men with metabolic syndrome (11).

Considering the factors contributing to the deterioration of fertility in obese men it should be mentioned (fig. 1):

– hypogonadotropic hypogonadism,

– increased aromatization of testosterone to estrogens,

– low sex hormone binding globulin (SHBG) serum levels,

– the deterioration of the quality of semen: reduction of the number of sperm and damage of their DNA,

– peripheral vascular disease leading to erectile dysfunction,

– remote impact of first and perhaps even second generation ancestors obesity (12, 13).

Spermatogenesis and sexual ability in men are strictly regulated by the hypothalamic-pituitary-gonadal axis hormones. In obesity which can be treated as a chronic inflammation state this control is disturbed. Excessively expanded and functionally changed adipose tissue becomes a source of many cytokines (adipokines). Some of them, i.e. tumor necrosis factor alpha (TNFα), interleukin 6 (Il-6) as well as several other factors inhibit the production of kisspeptin, a key protein in the mechanism of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus (14). This effect of adipokines activity is exacerbated by the estrogens. Higher levels of these hormones is a result of the increased aromatization from androgens in large amounts of fat tissue. It has been proved that estrogens, especially in low SHBG conditions actively inhibit the expression of kisspeptin (10). Leptin is an another factor contributing to low kisspeptin production. Although physiologically leptin stimulates GnRH secretion, in case of obesity leptin resistance develops with subsequent inhibition of gonadotropin-releasing hormone synthesis (15). It seems, that kisspeptin expression can be considered as the process that integrates the impact of obesity, testosterone deficiency and the effects of external factors on the hypothalamic-pituitary-gonadal axis. The corollary of the incorrect GnRH secretion is the hypogonadotropic hypogonadism with subsequent testosterone deficiency. In addition, there is a peripheral mechanism that contributes to low testosterone production. This mechanism is again associated with leptin, which blocks the effect of luteinizing hormone (LH) on the Leydig cells and on this way enhancing deficit of androgens (15). In turn, the reduction in the follicle stimulating hormone (FSH) secretion leads to decline in production of inhibin B in Sertoli cells. Inhibin B in normal state stimulates Leydig cells to testosterone secretion and is considered as an indicator of normal spermatogenesis. Its deficiency in obesity may be used as a marker of dysfunction of the seminiferous tubules and reduced number of Sertoli cells.

Male infertility is finally a result of abnormal spermatogenesis. The formation of sperm cells in the seminiferous tubules is a complex process regulated in auto-, para-, and endocrine manner. The key hormone in this process is testosterone, which affects the Sertoli and the epithelial cells of the seminiferous tubules. The Sertoli cells provide nutrients and support, being the only somatic cells in direct contact with developing germ cells. They also produce androgen-binding protein (ABP), which contributes towards a higher concentration of testosterone in testes. Moreover, the Sertoli cells secrete many other active biological substances, such as growth factors (TGFα, TGFβ, IGF) which regulate the process of spermatogenesis. In the early stages of prenatal life these cells synthesize anti-müllerian hormone (AMH), which inhibits the development of müllerian ducts exerting influence on the determination of sex. Testosterone also has an effect on other organs important for reproduction – seminal vesicles and tissues associated with erection.