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

Rehfeld, Anders; Egeberg, D. L.; Almstrup, Kristian; Petersen, Jørgen Holm; Dissing, Steen; Skakkebæk, Niels E.

doi:10.1530/ec-17-0156

Cited by 45 publications

(31 citation statements)

References 43 publications

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“…In addition, our results showed that the two most efficacious bisphenols at 10 µM, BPG and BPAF, could both increase sperm penetration into a viscous medium, like the response induced by the endogenous CatSper ligands progesterone and PGE1 ( Figure 5), and induce acrosome reaction in capacitated human sperm cells, similar to the response induced by progesterone ( Figure 6). Again, this is in line with previous studies where other environmental chemicals activating CatSper were found to exert progesterone-like effects on human sperm function (34,(36)(37)(38)56).…”

Section: Discussionsupporting

confidence: 92%

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

2020

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Aim: Evidence suggests that bisphenol A diglycidyl ether (BADGE), bisphenol A (BPA), and BPA analogs can interfere with human male fertility. However, the effect directly on human sperm function is not known. The CatSper Ca 2+ channel in human sperm controls important sperm functions and is necessary for normal male fertility. Environmental chemicals have been shown to activate CatSper and thereby affect Ca 2+ signaling in human sperm. BPA has previously been investigated for effects on Ca 2+ signaling human sperm, whereas the effects of other BPA analogs are currently unknown. The aim of this study is thus to characterize the effect of BADGE, BPA, and the eight analogs BPG, BPAF, BPC, BPB, BPBP, BPE, BPF, BPS on Ca 2+ signaling, and CatSper in human sperm. Methods: Direct effects of the bisphenols on Ca 2+ signaling in human sperm cells were evaluated using a Ca 2+ fluorimetric assay measuring changes in intracellular Ca 2+. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function was assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm-mucus penetration assay. Results: At 10 µM the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP induced Ca 2+ signals in human sperm cells, whereas BPE, BPF, BPS, and BPA had no effect. The efficacy of the chemicals at 10 µM is BPG > BPAF > BPC > BADGE > BPB > BPBP. Dose-response relations of BPG, BPAF, BPC, BADGE, BPB, and BPBP yielded EC50-values in the nM-µM range. The induced Ca 2+ signals were almost completely abolished using the CatSper inhibitor RU1968, indicating an effect of the bisphenols on CatSper. All bisphenols, except BPBP, were found to dose-dependently inhibit progesterone-induced Ca 2+ signals, with BPG and BPAF displaying inhibition even in low µM doses. BPG and BPAF were shown to affect human sperm function in a progesterone-like manner. Rehfeld et al. Bisphenols Activate Human CatSper Conclusion: Our results show that the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP can affect Ca 2+ signaling in human sperm cells through activation of CatSper. This could potentially disrupt human sperm function by interfering with normal CatSpersignaling and thus be a contributing factor in human infertility, either alone or in mixtures with other chemicals.

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Section: Discussionsupporting

confidence: 92%

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

2020

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“…It is known that chemicals in our environment, like UV-filters, can induce acrosomal exocytosis [25,26]. Such a mode of action may contribute (via the male partner) to the observed decline in fertility which has been described in many countries.…”

Section: Discussionmentioning

confidence: 99%

The Acrosomal Status of Density Purified Spermatozoa Differentiates Men from Couples in IVF and ICSI Treatment and Is Associated with Fecundity

Norup

Palme²,

Petersen

et al. 2020

JCM

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The acrosome of the spermatozoa is required for fertilization and in the raw ejaculate the percentage of viable acrosome-intact spermatozoa, the acrosomal status, is higher among men with good semen quality. Here we investigated if the acrosomal status of the processed semen preparations used at a fertility clinic can also be informative and whether it is associated with fecundity. The acrosomal status was measured by image cytometry on purified semen samples from couples during in vitro fertilization (IVF) (n = 99) and intracytoplasmic sperm injection (ICSI) (n = 107) treatment. Purified frozen-thawed donor samples were also analyzed (n = 199). In purified semen preparations the acrosomal status was significantly higher among sperm donors (p = 5.3 × 10−8) and men from IVF couples (p = 2.2 × 10−5) when compared to men from ICSI couples. A significant difference was also found between female, male and mixed factor infertility (p = 0.003). No association with lifestyle factors was found. In frozen-thawed donor samples, a significant positive (r = 0.16, p = 0.025) association with the number of pregnancies per sold straw was observed together with an area under the curve of 75.3%, when comparing the top and bottom deciles. Our results indicate that the acrosomal status may be a valuable parameter for personalizing fertility treatments and might be a good predictor of pregnancy success among normozoospermic men.

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“…Several studies investigating the endocrine disruption potential are available since the assessment performed by the Danish Centre on Endocrine Disrupters (Table ). In a recent in vitro study assessing the potential effects of chemical UV filters on human sperm, no effects on sperm acrosome reaction, sperm penetration, proportion of hyperactivated sperm cells or sperm viability were observed …”

Section: Endocrine Disruption Potentialmentioning

confidence: 99%

“…In a recent in vitro study assessing the potential effects of chemical UV filters on human sperm, no effects on sperm acrosome reaction, sperm penetration, proportion of hyperactivated sperm cells or sperm viability were observed. 15 The following studies are available on the ECHA website (unpublished studies as cited by ECHA, 2019 5 ) in order to assess the potential of endocrine activity of octocrylene. A uterotrophic assay, which is a short-term screening test to evaluate the ability of a chemical to elicit biological activities consistent with agonists or antagonists of natural oestrogens, was carried out in immature female rats (10 per dose) treated with octocrylene at doses of 250 and 1000 mg/kg bw/day via oral route.…”

Section: Endocrine Disruption Potentialmentioning

confidence: 99%

“…Undiluted octocrylene did not induce dermal or eye irritation in animal studies conducted in rabbits . In humans, irritant reactions with octocrylene are rare: in a multicentre study conducted in 30 centres across 12 European countries, only seven irritant reactions were observed in six of 1031 patients (0.6%) patch‐tested using 10% octocrylene in petrolatum for suspected photoallergic contact dermatitis…”

Section: Cutaneous Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Review of the safety of octocrylene used as an ultraviolet filter in cosmetics

Berardesca

Zuberbier

Viera³

et al. 2019

Acad Dermatol Venereol

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Octocrylene or octocrilene is an organic ultraviolet (UV) filter which absorbs mainly UVB radiation and short UVA wavelengths. It is used in various cosmetic products to either provide an appropriate sun protection factor in sunscreen products or to protect cosmetic formulations from UV radiation. There is no discussion that UV filters are beneficial ingredients in cosmetics since they protect from skin cancer, but octocrylene has been recently incriminated to potentially induce adverse effects on the endocrine system in addition to having allergic and/or photoallergic potential. However, the substance has the advantage to work synergistically with other filters allowing a beneficial broad photoprotection, e.g. it stabilizes the UVA filter avobenzone (i.e. butylmethoxydibenzoylmethane). Like all chemicals used in cosmetics, the safety profile of octocrylene is constantly under assessment by the European Chemical Agency (ECHA) since it has been registered according to the European regulation Registration, Evaluation, Authorisation and Restriction of Chemicals. Summaries of safety data of octocrylene are publicly available on the ECHA website. This review aims to present the main safety data from the ECHA website, as well as those reported in scientific articles from peer‐reviewed journals. The available data show that octocrylene does not have any endocrine disruption potential. It is a rare sensitizer, photocontact allergy is more frequent and it is considered consecutive to photosensitization to ketoprofen. Based on these results, octocrylene can be considered as safe when used as a UV filter in cosmetic products at a concentration up to 10%.

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

Cited by 45 publications

References 43 publications

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

The Acrosomal Status of Density Purified Spermatozoa Differentiates Men from Couples in IVF and ICSI Treatment and Is Associated with Fecundity

Review of the safety of octocrylene used as an ultraviolet filter in cosmetics

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