Dataset Information

Bisphenol A Diglycidyl Ether (BADGE) and Progesterone Do Not Induce Ca2+ Signals in Boar Sperm Cells.

ABSTRACT: Aim:Exposure of boar sperm cells to Bisphenol A diglycidyl ether (BADGE) has been shown to lead to reproductive failure in sows, however, the mode of action is unknown. As we have recently shown that BADGE can interfere with Ca2 + signaling in human sperm cells through an action on CatSper, and as CatSper has been shown to be expressed in boar sperm cells, we hypothesized that a similar mechanism in the boar sperm cells could be responsible for the reproductive failure. Methods:Direct effects of BADGE and the endogenous ligand of human CatSper, progesterone, on Ca2+ signaling in human and boar sperm cells were evaluated side-by-side using a Ca2+ fluorimetric assay measuring changes in intracellular Ca2+. Effects of BADGE on Ca2+ signaling in boar sperm were furthermore assessed by flow cytometry by an independent laboratory. Results:The exact same solutions of BADGE and progesterone induced transient biphasic Ca2+ signals in human sperm cells, but failed to do so in both non-capacitated and capacitated boar sperm cells. BADGE also failed to induce transient biphasic Ca2+ signals in boar sperm cells in the flow cytometric assay. Conclusion:BADGE and progesterone failed to induce Ca2+ signals in boar sperm cells. This indicates that the signaling mechanisms leading to activation of CatSper differs between human and boar sperm cells, and suggests that the mode of action by which exposure of boar sperm cells to BADGE can lead to reproductive failure in sows does not involve effects on Ca2+ signaling.

SUBMITTER: Rehfeld A

PROVIDER: S-EPMC7381341 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bisphenol A Diglycidyl Ether (BADGE) and Progesterone Do Not Induce Ca<sup>2+</sup> Signals in Boar Sperm Cells.

Rehfeld Anders A Mendoza Noelia N Ausejo Raquel R Skakkebæk Niels Erik NE

Frontiers in physiology 20200707

<h4>Aim</h4>Exposure of boar sperm cells to Bisphenol A diglycidyl ether (BADGE) has been shown to lead to reproductive failure in sows, however, the mode of action is unknown. As we have recently shown that BADGE can interfere with Ca<sup>2 +</sup> signaling in human sperm cells through an action on CatSper, and as CatSper has been shown to be expressed in boar sperm cells, we hypothesized that a similar mechanism in the boar sperm cells could be responsible for the reproductive failure.<h4>Met ...[more]

PMID: 32774306

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Project description: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 Ca2+ 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 Ca2+ signaling in human sperm. BPA has previously been investigated for effects on Ca2+ 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 Ca2+ signaling, and CatSper in human sperm. Methods: Direct effects of the bisphenols on Ca2+ signaling in human sperm cells were evaluated using a Ca2+ fluorimetric assay measuring changes in intracellular Ca2+. 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 ?M the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP induced Ca2+ signals in human sperm cells, whereas BPE, BPF, BPS, and BPA had no effect. The efficacy of the chemicals at 10 ?M is BPG > BPAF > BPC > BADGE > BPB > BPBP. Dose-response relations of BPG, BPAF, BPC, BADGE, BPB, and BPBP yielded EC50-values in the nM-?M range. The induced Ca2+ 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 Ca2+ signals, with BPG and BPAF displaying inhibition even in low ?M doses. BPG and BPAF were shown to affect human sperm function in a progesterone-like manner. Conclusion: Our results show that the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP can affect Ca2+ signaling in human sperm cells through activation of CatSper. This could potentially disrupt human sperm function by interfering with normal CatSper-signaling and thus be a contributing factor in human infertility, either alone or in mixtures with other chemicals.

Dataset Information

Bisphenol A Diglycidyl Ether (BADGE) and Progesterone Do Not Induce Ca2+ Signals in Boar Sperm Cells.

Publications

Bisphenol A Diglycidyl Ether (BADGE) and Progesterone Do Not Induce Ca<sup>2+</sup> Signals in Boar Sperm Cells.

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