Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic.

In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.

Vitku J ，Heracek J ，Sosvorova L ，Hampl R ，Chlupacova T ，Hill M ，Sobotka V ，Bicikova M ，Starka L ... -  《-》

Development and validation of LC-MS/MS method for quantification of bisphenol A and estrogens in human plasma and seminal fluid.

Bisphenol A (BPA) is a widely known endocrine disruptor with estrogenic, antiestrogenic or antiandrogenic properties. BPA could interfere with estrogen metabolism as well with receptor-mediated estrogen actions. Both environmental BPA and estrogens may be traced in body fluids, of which, besides the blood plasma, the seminal fluid is of particular interest regarding their possible interactions in the testis. The method for simultaneously determining BPA and estrogens is then needed, taking into account that their concentrations in these body fluid may differ. Here the method was developed and validated for measurements of BPA, estrone (E1), estradiol (E2) and estriol (E3) in blood plasma and seminal plasma using liquid chromatography-tandem mass spectrometry. Due to the phenolic moiety of all compounds, dansyl chloride derivatization could be used. The analytical criteria of the method with respect to expected concentration of the analytes were satisfactory. The lower limits of quantifications (LLOQ) amounted to 43.5, 4.0, 12.7, 6.7 pg/mL for plasma BPA, E1, E2 and E3, and 28.9, 4.9, 4.5, 3.4 pg/mL for seminal BPA, E1, E2 and E3, respectively. The concentrations of individual steroids differed between body fluids. To the best of our knowledge, this is the first method that enabled the measurement of estrogens and BPA together in one run. The concentrations of E1, E2 and for the first time also of E3 in seminal plasma in normospermic men are reported.

Vitku J ，Chlupacova T ，Sosvorova L ，Hampl R ，Hill M ，Heracek J ，Bicikova M ，Starka L ... -  《-》

Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility.

Vitku J ，Sosvorova L ，Chlupacova T ，Hampl R ，Hill M ，Sobotka V ，Heracek J ，Bicikova M ，Starka L ... -  《-》

Obesity aggravates toxic effect of BPA on spermatogenesis.

Both bisphenol A (BPA) and obesity affect male reproductive system. However, whether there is an interaction between them remains poorly understood. The aim of the present study was to evaluate the interaction between BPA exposure and obesity on semen quality and elucidate the mechanism in humans and animals. We firstly analyzed the interaction on semen volume, sperm count per ejaculate, sperm concentration and sperm motility in 357 men, and found that urinary BPA concentration was significantly correlated with sperm count per ejaculate in obese men (β=-34.62; 95% CI: -60.75, -8.48; P=0.01). Then we validated the interaction using lean and obese mice with administration of BPA. Significant interactions between BPA exposure and obesity on sperm count and sperm concentration was observed in mice. Finally, we conducted metabolomics analyses to identify metabolites related to the interaction. Metabolites related to the interaction, including capric acid, dodecanoic acid, l-palmitoylcarnitine, niacinamide, etc., are known to play critical roles in fatty acid oxidation and tricarboxylic acid cycle indicating increased oxidative stress associated with male reproductive dysfunction. Thus, our study finds an interaction between BPA exposure and obesity on sperm count and reveals potential metabolic mechanisms. It emphasizes the importance to study interactions between endocrine disrupting chemicals and obesity, and opens avenues for the possible use of animal models in identifying the interactions.

Hu W ，Dong T ，Wang L ，Guan Q ，Song L ，Chen D ，Zhou Z ，Chen M ，Xia Y ，Wang X ... -  《-》

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide dismutase, and catalase as well as the malondialdehyde and hydrogen peroxide concentrations in the testes and sperm. Melatonin sustained Bcl-2 expression and controlled apoptosis. Furthermore, melatonin maintained the testosterone levels, ameliorated histopathological changes, increased the percentages of seminal haploid germ cells, and protected sperm chromatin condensation process, indicating appropriate spermatogenesis with production of functional sperm. In conclusion, melatonin protected against BPA-induced apoptosis by controlling Bcl-2 expression and ameliorating oxidative stress in the testes and sperm. Thus, melatonin is a promising pharmacological agent for preventing the potential reproductive toxicity of BPA following occupational or environmental exposures.

Othman AI ，Edrees GM ，El-Missiry MA ，Ali DA ，Aboel-Nour M ，Dabdoub BR ... -  《-》