Bisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of daily necessities. Previous studies showed that BPA could impair spermatogenesis. However, its effects on mature spermatozoa are not well known. We aimed to investigate the in vivo and in vitro toxicity of BPA on mature mouse spermatozoa. Different doses of BPA (0, 10, 50, and 250 μg·kg(-1)·d(-1)) were administrated orally to C57BL/6 mice for 8 weeks. Subsequently, the sperm viability, motility, acrosome reaction (AR) ratio together with the expression/current levels of the sperm-specific Ca(2+ )channel (CatSper) and K(+ )channel (KSper) were examined. These parameters were also evaluated after applying BPA directly to normal mouse sperm to appraise the toxicity of BPA to mature sperm in vitro Significant decreases in sperm motility and AR were found in BPA administrated mice, possibly resulting from a BPA caused CatSper down-regulation which was supported by both western blot and patch clamping results. Moreover, direct application of BPA to spermatozoa inhibited CatSper transiently and also caused significant reductions in sperm total motility and AR ratio. In conclusion, both in vivo administration and in vitro application of BPA impair mature sperm functions by a CatSper-relevant mechanism.

Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice

“…The total sperm motility (%) before and after CdCl 2 addition was analyzed using a CASA system (WLJY-9000, China), as previously described [31]. For the in vitro study, sperm were incubated with different CdCl 2 concentrations (0, 10, 50, 250 µM) for 60 min at 37°C in 5% CO 2 .…”

“…The acrosome reaction was assessed by chlortetracycline (CTC) (Sigma, USA) staining as previously reported [31, 32]. Epididymal sperm were released and capacitated in HTF medium for 60 min in the presence or absence of CdCl 2 and progesterone (10 µM).…”

“…Further studies have also revealed that both CatSper and KSper are indispensable to male fertility and that any mutation of either channel will cause male infertility [30, 31]. …”

“…In this study, we aimed to evaluate changes in sperm function after exposure to cadmium and explore related mechanisms in vivo by orally administering cadmium chloride (CdCl 2 ) according to ref [31] and in vitro by applying 10, 50, and 250 µM CdCl 2 to sperm. Several sperm functions such as viability, motility, and acrosome reaction (AR) were examined.…”

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

“…As a known endocrine disruptor, BPA has been shown to interfere with hormonal and homeostatic systems, and BPA levels in human urine have been correlated with various diseases and adverse health outcomes (Braun et al, 2011;Carwile and Michels, 2011;Ehrlich et al, 2012;Lang et al, 2008;Lassen et al, 2014). BPA exposure has also been associated with reproductive dysfunctions, including reduction of testicular weight and sperm count, alterations of hormone levels, and impairment of spermatogenesis (Jin et al, 2013;Pacchierotti et al, 2008;Sakaue et al, 2001;Tiwari and Vanage, 2013;Wang et al, 2016). The mechanism of action of BPA has been investigated with respect to its estrogenic activity, such as effects on steroid hormone synthesis, and androgen receptor (AR) antagonism (Kitamura et al, 2005;Lee et al, 2003;Vinggaard et al, 2008;Zhang et al, 2011).…”