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UV filters in matched seminal fluid-, urine-, and serum samples from young men

Abstract

Recent in vitro studies have shown that some chemical UV filters mimic the effect of progesterone in the activation of the CatSper Ca2+ channel in human spermatozoa. However, so far, the extent of exposure of human spermatozoa to chemical UV filters via the presence of these chemicals in seminal fluid has been unknown. Here, we present levels of UV filters measured in human seminal fluid and comparisons to levels measured in concurrently collected urine and serum samples. In total nine UV filters were analysed by TurboFlow-LC–MS/MS in paired urine, serum, and seminal fluid samples from 300 young Danish men from the general population; each man collected one of each sample type within 1 h. The samples were collected during February–December 2013 and only six of the men reported having used sunscreen during the 48 h preceding the sample collection. Four of the examined UV filters could be detected in seminal fluid samples at levels above LOD in more than 10% of the samples. Benzophenone (BP), benzophenone-1 (BP-1), and benzophenone-3 (BP-3) were most frequently detected in, respectively, 18%, 19%, and 27% of the seminal fluid samples albeit at levels one to two orders of magnitude lower than the levels observed in urine. 4-methyl-benzophenone (4-MBP) was detectable in 11% of the seminal fluid samples while in <5% of the urine samples. Overall 45% of the men had at least one of the UV filters present in their seminal fluid at detectable levels. For BP-1 and BP-3 individual levels in urine and seminal fluid were significantly correlated, while this was not evident for BP nor 4-MBP. In conclusion, chemical UV filters are present in men’s seminal fluid; some of which can activate the human sperm-specific CatSper Ca2+ channel and thereby potentially interfere with the fertilisation process.

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Fig. 1: Venn-diagrams of the distribution of the UV filters in urine, serum, and seminal fluid: numbers indicate individuals with measurements above LOD in one, two, or three matrices.
Fig. 2: Relationships between individual UV filters in different matrices.

References

  1. 1.

    Krause M, Klit A, Blomberg Jensen M, Soeborg T, Frederiksen H, Schlumpf M, et al. Sunscreens: are they beneficial for health? An overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424–36.

    CAS  Google Scholar 

  2. 2.

    Kunz PY, Fent K. Multiple hormonal activities of UV filters and comparison of in vivo and in vitro estrogenic activity of ethyl-4-aminobenzoate in fish. Aquat Toxicol. 2006;79:305–24.

    CAS  Google Scholar 

  3. 3.

    Schlumpf M, Durrer S, Faass O, Ehnes C, Fuetsch M, Gaille C, et al. Developmental toxicity of UV filters and environmental exposure: a review. Int J Androl. 2008;31:144–51.

    CAS  Google Scholar 

  4. 4.

    Kim S, Choi K. Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: a mini-review. Environ Int. 2014;70:143–57.

    CAS  Google Scholar 

  5. 5.

    Watanabe Y, Kojima H, Takeuchi S, Uramaru N, Sanoh S, Sugihara K, et al. Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity. Toxicol Appl Pharmacol. 2015;282:119–28.

    CAS  Google Scholar 

  6. 6.

    Kinnberg KL, Petersen GI, Albrektsen M, Minghlani M, Awad SM, Holbech BF, et al. Endocrine-disrupting effect of the ultraviolet filter benzophenone-3 in zebrafish, Danio rerio. EnvironToxicol Chem. 2015;34:2833–40.

    CAS  Google Scholar 

  7. 7.

    Nakamura N, Inselman AL, White GA, Chang CW, Trbojevich RA, Sephr E, et al. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring. Birth Defects Res B Dev Reprod Toxicol. 2015;104:35–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Hoshino N, Tani E, Wako Y, Takahashi K. A two-generation reproductive toxicity study of benzophenone in rats. J Toxicol Sci. 2005;30:5–20.

  9. 9.

    Jeon HK, Sarma SN, Kim YJ, Ryu JC. Toxicokinetics and metabolisms of benzophenone-type UV filters in rats. Toxicology. 2008;248:89–95.

    CAS  Google Scholar 

  10. 10.

    Rehfeld A, Dissing S, Skakkebaek NE. Chemical UV filters mimic the effect of progesterone on Ca(2+) signaling in human sperm cells. Endocrinology. 2016;157:4297–308.

    CAS  Google Scholar 

  11. 11.

    Rehfeld A, Egeberg DL, Almstrup K, Petersen JH, Dissing S, Skakkebaek NE. EDC IMPACT: chemical UV filters can affect human sperm function in a progesterone-like manner. Endocr Connect. 2018;7:16–25.

    CAS  Google Scholar 

  12. 12.

    Schiffer C, Muller A, Egeberg DL, Alvarez L, Brenker C, Rehfeld A, et al. Direct action of endocrine disrupting chemicals on human sperm. EMBO Rep. 2014;15:758–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Publicover S, Harper CV, Barratt C. [Ca2+]i signalling in sperm–making the most of what you’ve got. Nat Cell Biol. 2007;9:235–42.

    CAS  Google Scholar 

  14. 14.

    Williams HL, Mansell S, Alasmari W, Brown SG, Wilson SM, Sutton KA, et al. Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa. Hum Reprod. 2015;30:2737–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Hildebrand MS, Avenarius MR, Fellous M, Zhang Y, Meyer NC, Auer J, et al. Genetic male infertility and mutation of CATSPER ion channels. Eur J Hum Genet. 2010;18:1178–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Avenarius MR, Hildebrand MS, Zhang Y, Meyer NC, Smith LL, Kahrizi K, et al. Human male infertility caused by mutations in the CATSPER1 channel protein. Am J Hum Genet. 2009;84:505–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Buck Louis GM, Kannan K, Sapra KJ, Maisog J, Sundaram R. Urinary concentrations of benzophenone-type ultraviolet radiation filters and couples’ fecundity. Am J Epidemiol. 2014;180:1168–75.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Bae J, Kim S, Kannan K, Buck Louis GM. Couples’ urinary concentrations of benzophenone-type ultraviolet filters and the secondary sex ratio. Sci Total Environ. 2016;543:28–36.

    CAS  Google Scholar 

  19. 19.

    Buck Louis GM, Chen Z, Kim S, Sapra KJ, Bae J, Kannan K. Urinary concentrations of benzophenone-type ultraviolet light filters and semen quality. Fertil Steril. 2015;104:989–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Adoamnei E, Mendiola J, Monino-Garcia M, Vela-Soria F, Iribarne-Duran LM, Fernandez MF, et al. Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men. Int J Hyg Environ Health. 2018;221:531–40.

    CAS  Google Scholar 

  21. 21.

    Chung MK, Buck Louis GM, Kannan K, Patel CJ. Exposome-wide association study of semen quality: systematic discovery of endocrine disrupting chemical biomarkers in fertility require large sample sizes. Environ Int. 2019;125:505–14.

    CAS  Google Scholar 

  22. 22.

    Kunisue T, Chen Z, Buck Louis GM, Sundaram R, Hediger ML, Sun L, et al. Urinary concentrations of benzophenone-type UV filters in U.S. women and their association with endometriosis. Environ Sci Technol. 2012;46:4624–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Pollack AZ, Mumford SL, Krall JR, Carmichael AE, Sjaarda LA, Perkins NJ, et al. Exposure to bisphenol A, chlorophenols, benzophenones, and parabens in relation to reproductive hormones in healthy women: a chemical mixture approach. Environ Int. 2018;120:137–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Janjua NR, Kongshoj B, Andersson AM, Wulf HC. Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol. 2008;22:456–61.

    CAS  Google Scholar 

  25. 25.

    Langford KH, Reid MJ, Fjeld E, Oxnevad S, Thomas KV. Environmental occurrence and risk of organic UV filters and stabilizers in multiple matrices in Norway. Environ Int. 2015;80:1–7.

    CAS  Google Scholar 

  26. 26.

    Schlumpf M, Kypke K, Wittassek M, Angerer J, Mascher H, Mascher D, et al. Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk: correlation of UV filters with use of cosmetics. Chemosphere. 2010;81:1171–83.

    CAS  Google Scholar 

  27. 27.

    Morrison GC, Beko G, Weschler CJ, Schripp T, Salthammer T, Hill J, et al. Dermal uptake of benzophenone-3 from clothing. Environ Sci Technol. 2017;51:11371–9.

    CAS  Google Scholar 

  28. 28.

    Wan Y, Xue J, Kannan K. Occurrence of benzophenone-3 in indoor air from Albany, New York, USA, and its implications for inhalation exposure. Sci Total Environ. 2015;537:304–8.

    CAS  Google Scholar 

  29. 29.

    Frederiksen H, Jensen TK, Jorgensen N, Kyhl HB, Husby S, Skakkebaek NE, et al. Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012. Reproduction. 2014;147:555–65.

    CAS  Google Scholar 

  30. 30.

    Moos RK, Angerer J, Wittsiepe J, Wilhelm M, Bruning T, Koch HM. Rapid determination of nine parabens and seven other environmental phenols in urine samples of German children and adults. Int J Hyg Environ Health. 2014;217:845–53.

    CAS  Google Scholar 

  31. 31.

    Wang L, Kannan K. Characteristic profiles of benzonphenone-3 and its derivatives in urine of children and adults from the United States and China. Environ Sci Technol. 2013;47:12532–8.

    CAS  Google Scholar 

  32. 32.

    Zhang T, Sun H, Qin X, Wu Q, Zhang Y, Ma J, et al. Benzophenone-type UV filters in urine and blood from children, adults, and pregnant women in China: partitioning between blood and urine as well as maternal and fetal cord blood. Sci Total Environ. 2013;461–462:49–55.

    Google Scholar 

  33. 33.

    Lu S, Long F, Lu P, Lei B, Jiang Z, Liu G, et al. Benzophenone-UV filters in personal care products and urine of schoolchildren from Shenzhen, China: Exposure assessment and possible source. Sci Total Environ. 2018;640-641:1214–20.

    CAS  Google Scholar 

  34. 34.

    Centers for Disease Control and Prevention (CDC). Fourth National report on Human Exposure to Environmental Chemicals, Updated tables, 2019. https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Jan2019-508.pdf.

  35. 35.

    Jorgensen N, Joensen UN, Jensen TK, Jensen MB, Almstrup K, Olesen IA, et al. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open. 2012;2:e000990. (p. 1–13).

  36. 36.

    Frederiksen H, Nielsen O, Skakkebaek NE, Juul A, Andersson AM. UV filters analyzed by isotope diluted TurboFlow-LC-MS/MS in urine from Danish children and adolescents. Int J Hyg Environ Health. 2017;220:244–53.

    CAS  Google Scholar 

  37. 37.

    Krause M, Frederiksen H, Sundberg K, Jorgensen FS, Jensen LN, Norgaard P, et al. Presence of benzophenones commonly used as UV filters and absorbers in paired maternal and fetal samples. Environ Int. 2018;110:51–60.

    CAS  Google Scholar 

  38. 38.

    Middleton DR, Watts MJ, Lark RM, Milne CJ, Polya DA. Assessing urinary flow rate, creatinine, osmolality and other hydration adjustment methods for urinary biomonitoring using NHANES arsenic, iodine, lead and cadmium data. Environ Health. 2016;15:68.

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Joensen UN, Frederiksen H, Blomberg Jensen M, Lauritsen MP, Olesen IA, Lassen TH, et al. Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men. Environ Health Perspect. 2012;120:1397–403.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Wang L, Asimakopoulos AG, Moon HB, Nakata H, Kannan K. Benzotriazole, benzothiazole, and benzophenone compounds in indoor dust from the United States and East Asian countries. Environ Sci Technol. 2013;47:4752–9.

    CAS  Google Scholar 

  41. 41.

    Brenker C, Rehfeld A, Schiffer C, Kierzek M, Kaupp UB, Skakkebaek NE, et al. Synergistic activation of CatSper Ca2+ channels in human sperm by oviductal ligands and endocrine disrupting chemicals. Hum Reprod. 2018;33:1915–23.

    CAS  Google Scholar 

  42. 42.

    Buck Louis GM, Barr DB, Kannan K, Chen Z, Kim S, Sundaram R. Paternal exposures to environmental chemicals and time-to-pregnancy: overview of results from the LIFE study. Andrology. 2016;4:639–47.

    CAS  Google Scholar 

  43. 43.

    Schlecht C, Klammer H, Frauendorf H, Wuttke W, Jarry H. Pharmacokinetics and metabolism of benzophenone 2 in the rat. Toxicology. 2008;245:11–7.

    CAS  Google Scholar 

  44. 44.

    Nakagawa Y, Suzuki T, Tayama S. Metabolism and toxicity of benzophenone in isolated rat hepatocytes and estrogenic activity of its metabolites in MCF-7 cells. Toxicology. 2000;156:27–36.

    CAS  Google Scholar 

  45. 45.

    Okereke CS, Abdel-Rhaman MS, Friedman MA. Disposition of benzophenone-3 after dermal administration in male rats. Toxicol Lett. 1994;73:113–22.

    CAS  Google Scholar 

  46. 46.

    Kadry AM, Okereke CS, Abdel-Rahman MS, Friedman MA, Davis RA. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97–102.

    CAS  Google Scholar 

  47. 47.

    International agency for research on cancer (IARC). Some chemicals present in industrial and consumer products, food and drinking-water. In: IARC monographs on the evaluation of carcinogenic risks to humans volume 101, 2012. https://publications.iarc.fr/125.

  48. 48.

    Ito R, Kawaguchi M, Koganei Y, Honda H, Okanouchi N, Sakui N, et al. Development of miniaturized hollow-fiber assisted liquid-phase microextraction with in situ acyl derivatization followed by GC-MS for the determination of benzophenones in human urine samples. Anal Sci. 2009;25:1033–7.

    CAS  Google Scholar 

  49. 49.

    Kawaguchi M, Ito R, Honda H, Koganei Y, Okanouchi N, Saito K, et al. Miniaturized hollow fiber assisted liquid-phase microextraction and gas chromatography-mass spectrometry for determination of benzophenone and derivates in human urine sample. J Chromatogr B Anal Technol Biomed Life Sci. 2009;877:298–302.

    CAS  Google Scholar 

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Acknowledgements

This project was supported by the Danish Environmental Protection Agency (j.nr.MST-621-00148) as a project under Centre on Endocrine Disrupters (http://www.cend.dk). We would like to thank the young men participating and the staff involved in different parts of the project including the recoupment procedures, physical examinations, collection, and analysis of samples.

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Correspondence to Hanne Frederiksen.

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Frederiksen, H., Krause, M., Jørgensen, N. et al. UV filters in matched seminal fluid-, urine-, and serum samples from young men. J Expo Sci Environ Epidemiol 31, 345–355 (2021). https://doi.org/10.1038/s41370-020-0209-3

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Keywords

  • UV filter
  • Benzophenone
  • Human biomonitoring
  • Endocrine disruptor
  • Seminal fluid
  • CatSper Ca2+ channel

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