Organic Ultraviolet Filters Mimic the Action of Progesterone on Human Sperm and Interfere with Sperm Functions

Program: Abstracts - Orals, Poster Previews, and Posters
Session: FRI 105-133-Endocrine Disrupting Chemicals and Gene Regulation and Development (posters)
Basic
Friday, April 1, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board FRI 121
Anders Rehfeld*1, Dorte Louise Egeberg1, Steen Dissing2 and Niels Erik Skakkebaek3
1University of Copenhagen, Faculty of Health and Medical Sciences, Rigshospitalet, Copenhagen, Denmark, 2University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark, 3University of Copenhagen, Faculty of Health and Medical Sciences, Rigshospitalet, Denmark, Copenhagen, Denmark
Background

Organic ultraviolet filters (UV filters) are widely used in sunscreens. Some UV filters are rapidly absorbed through the skin, have been measured in plasma (nM to µM range) and found in >95% of urine samples in the US, Spain, France and Denmark.

Hypothesis

We hypothesized that UV filters may mimic the physiological action of progesterone on the human sperm-specific CatSper Ca2+-channel. In our pilot study we found that CatSper is promiscuously activated by diverse chemicals, including several UV filters1.

Methods

We examined 29 of the 31 UV filters allowed in sunscreens in the US or the EU (the two remaining UV filters were not examined, as one could not be obtained and one could not be dissolved). We used Ca2+ fluorimetry to investigate the 29 UV filters for their ability to induce an Ca2+ influx in human sperm. Using CatSper inhibitors we examined whether the induced Ca2+ influx involved CatSper. Dose response relations were assessed for the Ca2+ influx inducing UV filters. These UV filters were also tested for their additivity in mixtures and competition with progesterone. Single sperm fluorescence microscopy was performed to examine the ability of the UV filters to induce an Ca2+influx at the estimated lowest effective dose. Finally, we tested the effect of all 29 UV filters on sperm motility, penetration in viscous media, viability and acrosomal exocytosis.

Results

We found that 13 of the 29 UV filters induced a mean Ca2+ influx > mean Ca2+ influx of the negative controls ±3SD (10 µM, n=3): 4-MBC, 3-BC, Octisalate, BCSA, Homosalate, Padimate O, Meradimate, BP-3, Octinoxate, Amiloxate, Octocrylene, Avobenzone, DHHB. The most efficient UV filters, 4-MBC and 3-BC, induced mean Ca2+ influxes at 10 µM reaching 97% and 92% respectively of the maximal Ca2+ influx induced by progesterone. Nine of the 13 UV filters were found to induce an Ca2+ influx by directly activating the CatSper channel (n=3). Dose response relations were assessed for the 13 UV filters, with mean EC50 values ranging from 0,417±1,23 to 7,014±1,18 µM and mean EC05 values (estimate for lowest effective dose) ranging from 0,009±1,95 to 0,575±1,16 µM (n≥3). In single sperm cells, 9 nM of 3-BC (the estimated EC05) was found to induce Ca2+influxes (n=5). The 13 UV filters acted additively in mixtures of 100 nM each (n=3). Some of the UV filters competitively inhibited the action of progesterone (n=3). Finally, we found effects of some UV filters on sperm motility, penetration in viscous media, viability and acrosomal exocytosis (n=3).

Conclusions

13 of 29 examined UV filters (44%) induced Ca2+ influxes in human sperms, at physiologically relevant doses. Nine UV filters activated the CatSper channel directly and thereby mimicked the effect of progesterone. Some of the UV filters were found to interfere with vital sperm functions in vitro. Clinical studies are needed to investigate if UV filters have effects on human fertility.

(1) Schiffer, C. et al. Direct action of endocrine disrupting chemicals on human sperm. EMBO Rep. (2014). doi:10.15252/embr.201438869

Nothing to Disclose: AR, DLE, SD, NES

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