BPA-Induced Deregulation Of Epigenetic Patterns: Effects On Female Zebrafish Reproduction

Abstract

Bisphenol A (BPA) is one of the commonest Endocrine Disruptor Compounds worldwide. It interferes with vertebrate reproduction, possibly by inducing deregulation of epigenetic mechanisms. To determine its effects on female reproductive physiology and investigate whether changes in the expression levels of genes related to reproduction are caused by histone modifications, BPA concentrations consistent with environmental exposure were administered to zebrafish for three weeks. Effects on oocyte growth and maturation, autophagy and apoptosis processes, histone modifications, and DNA methylation were assessed by Real-Time PCR (qPCR), histology, and chromatin immunoprecipitation combined with qPCR analysis (ChIP-qPCR). The results showed that 5 μg/L BPA down-regulated oocyte maturation-promoting signals, likely through changes in the chromatin structure mediated by histone modifications, and promoted apoptosis in mature follicles. These data indicate that the negative effects of BPA on the female reproductive system may be due to its upstream ability to deregulate epigenetic mechanism.

Zebrafish in Toxicology and Environmental Health

“…It is also present in the environment as a result of manufacturing processes and leaching from the products in which it is used. BPA is defined as an endocrine disruptor because of its ability to elicit both proestrogenic and antiestrogenic effects by binding to estrogen receptors ERα and ERβ and altering transcription in tissue- and context-specific manners (Santangeli et al, 2016). BPA binds to the zebrafish estrogen-related receptor gamma (ERRγ) in vivo (Tohmé et al, 2014).…”

“…Interestingly, this pathway is independent of signaling through the estrogen receptor (Fitzgerald et al, 2015). BPA is suggested to act through epigenetic mechanisms through histone modification and alteration of DNA methylation (Faulk et al, 2016; Kundakovic & Champagne, 2011; Santangeli et al, 2016), and zebrafish studies have provided key mechanistic insights. The effect of BPA on histone methylation patterns and DNA methylation has recently been shown in adult zebrafish (Laing et al, 2016; Santangeli et al, 2016).…”

“…BPA is suggested to act through epigenetic mechanisms through histone modification and alteration of DNA methylation (Faulk et al, 2016; Kundakovic & Champagne, 2011; Santangeli et al, 2016), and zebrafish studies have provided key mechanistic insights. The effect of BPA on histone methylation patterns and DNA methylation has recently been shown in adult zebrafish (Laing et al, 2016; Santangeli et al, 2016). Global DNA methylation has also recently been shown to be reduced in the ovaries and testes of adult zebrafish exposed to 15 μg/L BPA for 7 days (Liu, Zhang, et al, 2016) and 1 mg/L BPA for 15 days (Laing et al, 2016).…”

An old culprit but a new story: bisphenol A and “NextGen” bisphenols

“…However, estrogen receptor β (ER- β ) and aryl hydrocarbon receptor-mediated pathways have been implicated in fetal meiosis and adult follicle growth, respectively (31, 37). Importantly, experimental data suggest that BPA exposure also interferes with the epigenetic reprogramming of the female germline that occurs during follicle growth (38, 46) and in the early preimplantation embryo ([47] and reviewed in Eichenlaub-Ritter and Pacchierotti [48]). Although direct links between BPA, receptor signaling, and epigenetic modifications in the oocyte have not yet been delineated, the role of the epigenome in fetal development and adult disease makes this is a critical area of investigation.…”

Bisphenol A: Understanding Its Health Effects from the Studies Performed on Model Organisms

“…Activation of this pathway prevents the resumption of meiotic maturation in ish oocytes [83]. Study showed that BPA downregulated oocyte maturation-promoting signals through changes in the chromatin structure mediated by histone modiications in zebraish [85].…”