Rehfeld Anders, Mendoza Noelia, Ausejo Raquel, Skakkebæk Niels Erik
Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Front Physiol. 2020 Jul 7;11:785. doi: 10.3389/fphys.2020.00785. eCollection 2020.
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 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.
Direct effects of BADGE and the endogenous ligand of human CatSper, progesterone, on Ca signaling in human and boar sperm cells were evaluated side-by-side using a Ca fluorimetric assay measuring changes in intracellular Ca. Effects of BADGE on Ca signaling in boar sperm were furthermore assessed by flow cytometry by an independent laboratory.
The exact same solutions of BADGE and progesterone induced transient biphasic Ca 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 Ca signals in boar sperm cells in the flow cytometric assay.
BADGE and progesterone failed to induce Ca 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 Ca signaling.
已证明将公猪精子细胞暴露于双酚A二缩水甘油醚(BADGE)会导致母猪繁殖失败,但其作用方式尚不清楚。由于我们最近表明BADGE可通过作用于CatSper来干扰人类精子细胞中的钙信号,并且已证明CatSper在公猪精子细胞中表达,我们推测公猪精子细胞中类似的机制可能是繁殖失败的原因。
使用测量细胞内钙变化的钙荧光测定法,并排评估BADGE和人类CatSper的内源性配体孕酮对人类和公猪精子细胞中钙信号的直接影响。此外,由独立实验室通过流式细胞术评估BADGE对公猪精子中钙信号的影响。
相同浓度的BADGE和孕酮溶液可在人类精子细胞中诱导瞬时双相钙信号,但在未获能和获能的公猪精子细胞中均未成功诱导。在流式细胞术测定中,BADGE也未能在公猪精子细胞中诱导瞬时双相钙信号。
BADGE和孕酮未能在公猪精子细胞中诱导钙信号。这表明导致CatSper激活的信号传导机制在人类和公猪精子细胞之间存在差异,并表明公猪精子细胞暴露于BADGE会导致母猪繁殖失败的作用方式不涉及对钙信号的影响。