Chemical UV Filters Mimic the Effect of Progesterone on Ca2+ Signaling in Human Sperm Cells

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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.

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