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

EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner

“…We were able to obtain 30, out of the 31 chemical UV filters allowed in sunscreens in the EU and/or US ( Table 1 ) from various chemical providers and to dissolve 29 of these in DMSO or ethanol as previously described ( 21 ). Progesterone, ionomycin, fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and 4000 cP methylcellulose were obtained from Sigma–Aldrich.…”

“…CatSper can be promiscuously activated by various ligands ( 16 ), including multiple EDCs ( 17 , 18 , 19 , 20 , 21 ). Our recent study examined 29 of the 31 chemical UV filters allowed in sunscreens in the EU and/or US for their ability to induce a rise in [Ca 2+ ] i in human sperm cells and showed that 13 chemical UV filters induced a rise in [Ca 2+ ] i in human sperm cells ( 21 ). Nine of these seemed to induce a Ca 2+ influx through interaction with CatSper, thereby mimicking the effect of progesterone.…”

The Catsper channel and its roles in male fertility: a systematic review

“…Progesterone surrounds the egg in the female reproductive tract and is released by cumulus cells. Progesterone induces Ca 2+ entry into sperm through the Catsper channel and thus promotes the acrosome reaction [ 76 , 77 ]. How specifically progesterone regulates Ca 2+ concentration has been deeply investigated.…”

Dermal Uptake of Benzophenone-3 from Clothing

“…The endocrine disrupting ability of BP-3 was recently confirmed in a study showing a skewed sex ratio favoring females in zebrafish following developmental exposure 7 . In addition, recent in vitro studies have shown that BP-3 and some other chemical UV filters mimic the effect of progesterone on the CatSper Ca 2+ channel in human sperm cell, triggering multiple sperm cell functions essential for fertilization of the egg and exposure to BP-3 is therefore suspected to impact on male fertility 8 . Furthermore, the major metabolite of BP-3, 2,4-dihydroxybenzophenone or benzophenone-1 (BP-1), is a suspected endocrine disruptor and is included on the Substitute it Now (SIN) list 6 .…”