The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model

Abstract

this study aimed to examine the impact of BpA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRnAs (miRnAs) related to heart development and diseases. Pregnancy is known to be the "critical windows" in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BpA. BpA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRnAs expression in cardiac of mother-and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p,-208-3p, and-210-3p expressions were observed in all heart of the foetuses from BpA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRnAs with histological changes were observed in both mother-and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life. Altered foetal development "programming" may predispose certain individuals to the risk of chronic disease development later in their life. This was suggested by Barker and co-worker who presented the first finding on the increased risk of cardiovascular disease (CVD) in children of malnourished mothers 1. Barker then further extended his theory and linked the CVD development and insulin resistance to the environment of the placenta. His findings have attracted another study to report on the insufficiency of uteroplacental of malnutrition mothers increases the risk of the offspring to type 2 diabetes 2. Another study demonstrated that miR-208, a

Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A

“…Hu et al (2016) demonstrated that the increased myocardial collagen content in mice exposed to BPA is associated with MAPK ERK1/2 signaling pathway activation and with increased expression of the profibrotic factor TGF-β1. Also, prenatal exposure to BPA leads to fibrosis in fetal heart that was not associated with hepatotoxicity (Rasdi et al, 2020). Our study showed that short-term BPA exposure enhances the gene expression of CTGF while TGF-β1 was upregulated in the malnourished background only.…”

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes

“…B. Rasdi et al, 2020) and decrease (Belcher et al, 2015) blood pressure in rodent models. Although this discrepancy may be attributed to experimental design, which include different doses, treatment duration, and animals of differing age.…”

“…BPA‐exposed female offspring were at increased risk for cardiomyopathy, and both male and female offspring were prone to myocardial degeneration with signs of inflammatory cell infiltration. Rasdi et al also reported an increase in maternal and fetal cardiac fibrosis following intrauterine BPA exposure (Rasdi et al, 2020). At higher BPA concentrations (50,000 μg kg −1 day −1 ), focal inflammation was observed in the cardiac tissue of pregnant mice, which coincided with slowing of cardiac electrical conduction and increased systolic and diastolic pressure relative to vehicle control (Valokola et al, 2019).…”

“…This is an area of research that requires additional attention—as BPA exposure has been shown to both increase (B. B. Patel, Raad, et al, 2015; Rasdi et al, 2020) and decrease (Belcher et al, 2015) blood pressure in rodent models. Although this discrepancy may be attributed to experimental design, which include different doses, treatment duration, and animals of differing age.…”

White rot fungi can be a promising tool for removal of bisphenol A, bisphenol S, and nonylphenol from wastewater

“…Bisphenol A has become one of the most intensively manufactured chemicals in the world due to demonstrating the finest properties for plastic production (Noszczyńska and Piotrowska-Seget 2018 ). Numerous studies have investigated BPA effects on the human body and animals (Zhu et al 2015 ; Quesada et al 2002 ; Braun et al 2009 ; Izzotti et al 2009 ; Pfeifer et al 2015 ; Leung et al 2017 ; Maćczak et al 2017 ; Pinney et al 2017 ; Tian et al 2018 ; Grandin et al 2019 ; Özel et al 2019 ; Gao et al 2020 ; Rasdi et al 2020 ; Tassinari et al 2020 ; Wu and Seebacher 2020 ; Wu et al 2020a ; Pan et al 2020 ). Since BPA has a comparable structure to that of natural estrogen 17β-estradiol, it can bind to ERα and ERβ, though with 1000-fold less affiliation than estradiol (Gray et al 2004 ; vom Saal and Hughes 2005 ; Takayanagi et al 2006 ; Gray et al 2004 ; vom Saal and Hughes 2005 ; Takayanagi et al 2006 ).…”