title: Chemical UV Filters Mimic the Effect of Progesterone on Ca2+Signaling in Human Sperm Cells.
abstract: Progesterone released by cumulus cells surrounding the egg induces a Ca2+influx into human sperm cells via the cationic channel of sperm (CatSper) Ca2+channel and controls multiple Ca2+-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca2+signaling in human sperm cells. We examined 29 UV filters allowed in sunscreens in the United States and/or the European Union for their ability to induce Ca2+signals in human sperm by applying measurements of the intracellular free Ca2+concentration. We found that 13 UV filters induced a significant Ca2+signal at 10 μM. Nine UV filters induced Ca2+signals primarily by activating the CatSper channel. The UV filters 3-benzylidene camphor (3-BC) and benzylidene camphor sulfonic acid competitively inhibited progesterone-induced Ca2+signals. Dose-response relations for the UV filters showed that the Ca2+signal-inducing effects began in the nanomolar-micromolar range. Single-cell Ca2+measurements showed a Ca2+signal-inducing effect of the most potent UV filter, 3-BC, at 10 nM. Finally, we demonstrated that the 13 UV filters acted additively in low-dose mixtures to induce Ca2+signals. In conclusion, 13 of 29 examined UV filters (44%) induced Ca2+signals in human sperm. Nine UV filters primarily activated CatSper and thereby mimicked the effect of progesterone. The UV filters 3-BC and benzylidene camphor sulfonic acid competitively inhibited progesterone-induced Ca2+signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility.
authors: Department of Growth and Reproduction (A.R., N.E.S.), Copenhagen University Hospital, Rigshospitalet, Department of Cellular and Molecular Medicine (A.R., S.D.), Faculty of Health Sciences, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (A.R., N.E.S.), Rigshospitalet, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors: A
authors: A
authors: Rehfeld
authors: Department of Growth and Reproduction (A.R., N.E.S.), Copenhagen University Hospital, Rigshospitalet, Department of Cellular and Molecular Medicine (A.R., S.D.), Faculty of Health Sciences, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (A.R., N.E.S.), Rigshospitalet, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors: S
authors: S
authors: Dissing
authors: Department of Growth and Reproduction (A.R., N.E.S.), Copenhagen University Hospital, Rigshospitalet, Department of Cellular and Molecular Medicine (A.R., S.D.), Faculty of Health Sciences, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (A.R., N.E.S.), Rigshospitalet, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors: N E
authors: NE
authors: Skakkebæk
mesh_terms: D001593:Benzyl Compounds / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002164:Camphor / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011374:Progesterone / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001593:Benzyl Compounds; D001597:Benzylidene Compounds; C511303:3-benzylidene camphor; D011374:Progesterone; D002164:Camphor; D002118:Calcium