Abstract
Lifestyle, environment and excess body weight are not only associated with an increased risk of metabolic disorders, such as type 2 diabetes, but also to other pathological processes, such as infertility. A hormone produced mainly by the liver called fibroblast growth factor 21 (FGF21) is closely linked to the energy status and is increased in patients suffering from obesity or insulin resistance. Recently, FGF21 has been shown to be associated with female fertility disorders, but no or few data about the role of FGF21 on human male fertility has been described. In the present study, FGF21 was measured in the seminal fluid at a lower level in comparison to the blood level. Thus, in the present in vitro study, we aimed to decipher the FGF21 system in human semen. To evaluate the putative role of FGF21 on spermatozoa function, we incubated human spermatozoa with increasing concentrations of recombinant human FGF21. The FGF21 in seminal fluid is potentially produced by male reproductive tract tissues. In spermatozoa, the FGF21 signal was transduced by the two main receptors FGFR1-c and FGFR3 and the cofactor β-klotho, which are colocalized in the middle piece of spermatozoa and stimulated the PI3K/Akt and MAPK pathways. Finally, in vitro treatment by FGF21 significantly increased sperm motility and ATP levels. Concomitantly, exposure to FGF21 improved the oxidative stress, as a lower ROS level was observed. Overall, these results seem to indicate that the metabolic factor, FGF21, positively modifies the activity and quality of the parameters of human spermatozoa.
Highlights
Infertility is a public health problem that affects about 15% of couples of childbearing age
We observed that the fibroblast growth factor 21 (FGF21) concentration was nearly 12 to 28 times lower in the seminal fluid as compared to that in the plasma, and the FGF21 seminal fluid/FGF21 plasma ratio was lower in obese patients (Figure 1B)
We demonstrated the presence of FGF21 in human seminal fluid and argued that seminal FGF21 could be produced by the different tissues of the male reproductive tract
Summary
Infertility is a public health problem that affects about 15% of couples of childbearing age. In almost 50% of cases, the male factor is involved [1]. Public health authorities note an increase in the use of conception centers by patients with metabolic disorders, such as obesity/insulin resistance. FGF21 Effects on Human Spermatozoa between energy metabolism and reproductive activity, involving both nutritional and hormonal regulations. Recent data support that a hormone produced mainly by the liver called fibroblast growth factor 21 (FGF21), is involved in female fertility disorders such as polycystic ovary syndrome [3,4,5,6], suggesting its contribution to the control of female fertility and raises the question about its involvement in male fertility
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