Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations.

Adoamnei E ，Mendiola J ，Moñino-García M ，Vela-Soria F ，Iribarne-Durán LM ，Fernández MF ，Olea N ，Jørgensen N ，Swan SH ，Torres-Cantero AM ... -  《-》

Urinary concentrations of parabens and reproductive parameters in young men.

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that are commonly added to personal care products, cosmetics, pharmaceuticals and beverage and food processing as antimicrobial preservatives. Parabens have been reported to show estrogenic effects and affect male reproduction function in animal models, but human epidemiologic studies are still scarce. The objective of this study was to examine associations between urinary concentrations of parabens and semen quality and reproductive hormone levels. This was a cross-sectional study with 215 young university students (18-23years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary paraben concentrations (methylparaben, ethylparaben, propylparaben and butylparaben) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm concentration, total sperm count (TSC), motility and morphology following WHO guidelines. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and estradiol using immunoassays. Associations between urinary concentrations of parabens and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential covariates. Ninety-four percent of the men had detectable urinary concentrations of parabens. After taking into account important covariates, urinary concentrations of parabens or their molar sum were not significantly associated with any semen parameters or any of the reproductive hormone levels. Relative to men in the lowest quartile of sum of urinary paraben concentrations, the adjusted difference (95% CI) of TSC (millions) for men in the 2nd, 3rd, and 4th quartiles were 4.1% (-37.1;45.3), -1.6% (-41.9;38.8), and -9.8% (-52.5;32.8), respectively (P-trend=0.55). Our results suggest that, in young men, urinary parabens may not adversely impact reproductive function, but further research is warranted to confirm these findings in other male populations.

Adoamnei E ，Mendiola J ，Moñino-García M ，Vela-Soria F ，Iribarne-Durán LM ，Fernández MF ，Olea N ，Jørgensen N ，Swan SH ，Torres-Cantero AM ... -  《-》

Urinary bisphenol A concentrations are associated with reproductive parameters in young men.

Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region). All subjects provided urine, blood serum and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, concentration, motility, morphology and total sperm count (TSC). Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B and estradiol. Relationships between urinary BPA concentrations and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders and covariates. Ninety-five percent of the men had detectable urinary BPA concentrations with unadjusted median (5th-95th) of 2.8 (0.16-11.5) ng/mL. After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (β = 0.07, 95%CI: 0.02;0.12, p-value < 0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (β = - 0.04, 95%CI: - 0.07;- 0.02, p-value < 0.01) and TSC (β = - 0.05, 95%CI: - 0.08;- 0.02, p-value < 0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Our results support the hypothesis that BPA exposure may be associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm counts in young men.

Adoamnei E ，Mendiola J ，Vela-Soria F ，Fernández MF ，Olea N ，Jørgensen N ，Swan SH ，Torres-Cantero AM ... -  《-》

Urinary concentrations of benzophenone-type ultraviolet light filters and semen quality.

To assess benzophenone-type ultraviolet (UV) filter concentrations, chemicals used in sunscreen and personal care products, and semen endpoints. Cohort. Not applicable. A total of 413 men provided semen and urine samples, 2005-2009. Five UV filters were quantified (ng/mL) in urine using liquid chromatography-triple quadrupole mass spectrometry: BP-1 (2,4-dihydroxybenzophenone), BP-2 (2,2',4,4'-tetrahydroxybenzophenone), BP-3 (2-hydroxy-4-methoxybenzophenone), BP-8 (2,2'-dihydroxy-4-methoxybenzophenone), and 4-OH-BP (4-hydroxybenzophenone). Using linear regression, β-coefficients (β) and 95% confidence intervals (CIs) for each chemical dichotomized at the 75th percentile and Box-Cox transformed semen endpoint were estimated, after adjusting for age, body mass index, cotinine, season, and site. None. Thirty-five semen endpoints. BP-2 was associated with diminished sperm concentration (β = -0.74; 95% CI -1.41, -0.08), straight (β = -4.57; 95% CI -8.95, -0.18) and linear movement (β = -3.15; 95% CI -6.01, -0.30), more immature sperm (β = 0.38; 95% CI 0.15, 0.62), and a decreased percentage of other tail abnormalities (β = -0.16; 95% CI -0.31, -0.01). BP-8 was associated with decreased hypo-osmotic swelling (β = -2.57; 95% CI -4.86, -0.29) and higher acrosome area (β = 1.14; 95% CI 0.01, 2.26). No associations were observed for BP-1, BP-3, or 4OH-BP. The findings suggest that specific UV filters may be associated with some aspects of semen endpoints, but await future corroboration.

Buck Louis GM ，Chen Z ，Kim S ，Sapra KJ ，Bae J ，Kannan K ... -  《-》

Reproductive hormones of ICSI-conceived young adult men: the first results.

Are reproductive hormone levels (FSH, LH, inhibin B and testosterone) in male offspring conceived by ICSI because of male infertility comparable with those from peers born after spontaneous conception? In this cohort of 54 young men conceived by ICSI because of male-factor infertility, mean and median reproductive hormone levels were found to be comparable with results from spontaneously conceived peers, but ICSI-conceived men were more likely to have low inhibin B (<10th percentile) and high FSH (>90th percentile) levels. Since the worldwide oldest ICSI offspring have recently reached young adulthood, their reproductive health can now be investigated. This typically involves semen analysis and a hormonal profiling including the measurement of FSH, LH, inhibin B and testosterone. Circulating levels of FSH and inhibin B are generally known as markers of the exocrine function of the testis, i.e. spermatogenesis, while LH and testosterone reflect its endocrine function. We have previously observed a normal pubertal development and comparable levels of inhibin B and testosterone among pubertal ICSI boys when compared to spontaneously conceived peers. However, at present, information on the gonadal function of ICSI offspring in adulthood is still lacking. This study, conducted between March 2013 and April 2016 at the UZ Brussel, is part of a larger follow-up project focusing on reproductive and metabolic health of young adults between 18 and 22 years and conceived after ICSI because of male infertility. The ICSI men are part of a longitudinally followed cohort while the spontaneously conceived controls were recruited cross-sectionally. Results of a single fasting blood sample from 54 young adult ICSI men were compared to that of 57 spontaneously conceived peers. Reproductive hormone analysis involved FSH, LH, testosterone and inhibin B measurement. Furthermore, the association between their reproductive hormones and their sperm parameters was examined. Data were analyzed by multiple linear and logistic regression adjusted for covariates. ICSI men had comparable mean levels of FSH, LH, testosterone and inhibin B in comparison to spontaneously conceived counterparts, even after adjustment for confounders, such as age, BMI and season. Young ICSI-conceived men were more likely to have inhibin B levels below the 10th percentile (<125.2 ng/l; Adjusted Odds Ratio (AOR) 4.0; 95% CI: 0.9-18.4; P = 0.07) compared with spontaneously conceived peers and were more likely to have FSH levels above the 90th percentile (>5.5 IU/L; AOR 3.3; 95% CI: 0.9-11.9; P = 0.06) compared with spontaneously conceived peers, but neither difference reached statistical significance. FSH, LH and inhibin B, but not testosterone, levels were significantly associated with sperm concentration and total sperm count. The main limitation is the small study population. Furthermore, the results of this study should be interpreted according to the background of the participants: all subjects in our study group were conceived by ICSI because of severe male infertility and hence the results cannot be generalized to all ICSI offspring because the indications for performing ICSI have since been widened. These first results in a small group of ICSI men show reassuring reproductive hormonal levels. However, larger studies are required to confirm our results. Since inhibin B and FSH are consistently correlated with semen characteristics, we would suggest that the reproductive status of young adults conceived by ICSI is explored with a hormonal assessment given its easier acceptance compared to semen sampling. This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). A grant from the Belgian Society for Pediatric Endocrinology and Diabetology was received for this project. All co-authors, except M.B. and H.T., declare no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection. The institution of HT receives research grants from the 'Research Fund of Flanders' (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility. N/A.

Belva F ，Roelants M ，De Schepper J ，Van Steirteghem A ，Tournaye H ，Bonduelle M ... -  《-》