Chemical UV Filters Mimic the Effect of Progesterone on Ca super(2+) Signaling in Human Sperm Cells

Progesterone released by cumulus cells surrounding the egg induces a Ca super(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca super(2+) channel and controls multiple Ca super(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filter...

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Published in:Endocrinology (Philadelphia) Vol. 157; no. 11; pp. 4297 - 4308
Main Authors: Rehfeld, A, Dissing, S, Skakkebaek, N E
Format: Journal Article
Language:English
Published: 01-11-2016
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Summary:Progesterone released by cumulus cells surrounding the egg induces a Ca super(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca super(2+) channel and controls multiple Ca super(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca super(2+) 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 Ca super(2+) signals in human sperm by applying measurements of the intracellular free Ca super(2+) concentration. We found that 13 UV filters induced a significant Ca super(2+) signal at 10 [mu]M. Nine UV filters induced Ca super(2+) signals primarily by activating the CatSper channel. The UV filters 3-benzylidene camphor (3-BC) and benzylidene camphor sulfonic acid competitively inhibited progesterone-induced Ca super(2+) signals. Dose-response relations for the UV filters showed that the Ca super(2+) signal-inducing effects began in the nanomolar-micromolar range. Single-cell Ca super(2+) measurements showed a Ca super(2+) 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 Ca super(2+) signals. In conclusion, 13 of 29 examined UV filters (44%) induced Ca super(2+) 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 Ca super(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility.
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ISSN:0013-7227
1945-7170
DOI:10.1210/en.2016-1473