TY - JOUR

T1 - Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

AU - Rehfeld, A

AU - Dissing, S

AU - Skakkebæk, N E

PY - 2016/11

Y1 - 2016/11

N2 - Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca(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(2+) signals in human sperm by applying measurements of the intracellular free Ca(2+) concentration. We found that 13 UV filters induced a significant Ca(2+) signal at 10 μM. Nine UV filters induced Ca(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(2+) signals. Dose-response relations for the UV filters showed that the Ca(2+) signal-inducing effects began in the nanomolar-micromolar range. Single-cell Ca(2+) measurements showed a Ca(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(2+) signals. In conclusion, 13 of 29 examined UV filters (44%) induced Ca(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(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility.

AB - Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca(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(2+) signals in human sperm by applying measurements of the intracellular free Ca(2+) concentration. We found that 13 UV filters induced a significant Ca(2+) signal at 10 μM. Nine UV filters induced Ca(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(2+) signals. Dose-response relations for the UV filters showed that the Ca(2+) signal-inducing effects began in the nanomolar-micromolar range. Single-cell Ca(2+) measurements showed a Ca(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(2+) signals. In conclusion, 13 of 29 examined UV filters (44%) induced Ca(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(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility.

U2 - 10.1210/en.2016-1473

DO - 10.1210/en.2016-1473

M3 - Journal article

C2 - 27583790

VL - 157

SP - 4297

EP - 4308

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 11

ER -