Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

Abstract

The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states.

Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes

“…The dysfunctions of the ECM components have been observed in numerous diseases, including Lyme disease, chronic inflammatory response syndrome, and adenocarcinoma, as well as in AVV defects 26 . A similar observation was made for the plastic monomer bisphenol A, which caused ECM deficiency and structural defects of the AVV in zebrafish 27 …”

Fast, efficient and clean adsorption of bisphenol-A using renewable mesoporous silica nanoparticles from sugarcane waste ash

“…To measure the absorbance of samples aer BPA adsorption, they were centrifuged at 1560g, the supernatant was removed, and then, their absorbance was measured. 23 The amount of BPA removal was expressed as the removal percentage of contaminants and calculated by the eqn (1).…”

“…Bisphenol-A (BPA) is an endocrine disruptive compound (EDC) that may mimic or interfere with the endocrine or hormonal system. 1 BPA was rst synthesized in 1891 by Dianin 2 but its synthesis was rst reported only in 1905 by Zincke. 3 BPA was widely used in the manufacture of thermal paper, 4 food storage containers, baby bottles, reusable drink containers, toys, dish and laundry detergents, bar soaps, shampoo, shaving cream, face cleansers, sunscreen lotions, etc.…”

“…5 Some effects of BPA on health are sexual dysfunction and fertility; metabolic disease, such as, obesity; cancer (breast cancer, neuroblastoma); neurological effects (disruption of the dopaminergic system); cardiovascular diseases; thyroid disorders and asthma. 1,6 BPA can also alter plasma sex hormones levels in shes 7 and cause adverse effects in the development and reproduction of the nonmammalian aquatic vertebrates, including reduced male hormones, testicular cell death, decreased sperm density and motility, inhibition of spermatogenesis and egg production. 8 Nowadays most plastic containers and personal care products are produced without BPA.…”

A suggested bisphenol A metabolite (MBP) interfered with reproductive organ development in the chicken embryo while a human-relevant mixture of phthalate monoesters had no such effects

“…Further investigation suggested that the enhanced estrogenic activity was induced by 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) (Yoshihara et al 2004). The estrogenic activity of MBP was noted in vivo in fish (Brown et al 2019;Ishibashi et al 2005;Moreman et al 2018) and ovariectomized rats (Okuda, Takiguchi, and Yoshihara 2010) where it was 250-1000-fold more potent than BPA. Exposure to MBP induced cell proliferation and reduced protein levels of ERα in a human breast cancer cell line (Hirao-Suzuki et al 2019).…”