scholarly journals Bisphenol A Alters Autonomic Tone and Extracellular Matrix Structure and Induces Sex-Specific Effects on Cardiovascular Function in Male and Female CD-1 Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 882-895 ◽  
Author(s):  
Scott M. Belcher ◽  
Robin B. Gear ◽  
Eric L. Kendig

Abstract The aim of this study was to determine whether bisphenol A (BPA) has adverse effects on cardiovascular functions in CD-1 mice and define sex-specific modes of BPA action in the heart. Dams and analyzed progeny were maintained on a defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) that resulted in BPA exposures from 4–5 to approximately 5000 μg/kg · d or a diet containing 17α-ethinyl estradiol (EE; ∼0.02, 0.2, and 0.15 μg/kg · d) as an oral bioavailable estrogen control. Assessment of electrocardiogram parameters using noninvasive methods found that ventricular functions in both male and female mice were not altered by either BPA or EE. However, exposure-related changes in the rates of ventricular contraction, suggestive of a shift in sympathovagal balance of heart rate control toward increased parasympathetic activity, were detected in males. Decreased systolic blood pressure was observed in males exposed to BPA above 5 μg/kg · d and in females from the highest BPA exposure group. Morphometric histological measures revealed sexually dimorphic changes in the composition of the cardiac collagen extracellular matrix, increases in fibrosis, and evidence of modest exposure-related remodeling. Experiments using the α-selective adrenergic agonist phenylephrine found that BPA enhanced reflex bradycardia in females, but not males, revealed that BPA and EE exposure sex specifically altered the sympathetic regulation of the baroreflex circuits. Increased sensitivity to the cardiotoxic effects of the β-adrenergic agonist isoproterenol was observed in BPA- and EE-exposed females. This effect was not observed in males, in which BPA or EE exposures were protective of isoproterenol-induced ischemic damage and hypertrophy. The results of RNA sequence analysis identified significant sex-specific changes in gene expression in response to BPA that were consistent with the observed exposure-related phenotypic changes in the collagenous and noncollagenous extracellular matrix, cardiac remodeling, altered autonomic responses, changes in ion channel and transporter functions, and altered glycolytic and lipid metabolism.

2017 ◽  
Vol 5 (3) ◽  
pp. e13133 ◽  
Author(s):  
Sarah A. Johnson ◽  
William G. Spollen ◽  
Lindsey K. Manshack ◽  
Nathan J. Bivens ◽  
Scott A. Givan ◽  
...  

2017 ◽  
Author(s):  
Robin B. Gear ◽  
Scott M. Belcher

ABSTRACTThe endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17α-ethinyl estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite ubiquitous human exposure to BPA, and the wide-spread clinical use of EE as oral contraceptive adjuvant, the impact of these estrogenic endocrine disrupting chemicals (EDCs) on the immune system is unclear. Here we report results of in vivo dose response studies that analyzed the histology and microstructural changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000 μg/kg/day BPA or 0.02 to 2 μg/kg/day EE from conception until 12-14 weeks of age. Results of that analysis indicate that both BPA and EE have dose- and sex-specific impacts on the cellular and microanatomical structures of the spleens that reveal minor alterations in immunomodulatory and hematopoietic functions. These findings support previous studies demonstrating the murine immune system as a sensitive target for estrogens, and that oral exposures to BPA and EE can have estrogen-like immunomodulatory affects in both sexes.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 781 ◽  
Author(s):  
Katherine F. Wallis ◽  
Stepan B. Melnyk ◽  
Isabelle R. Miousse

Dietary methionine restriction is associated with improved health outcomes and an increase in lifespan in animal models. We have previously shown that an increase in dietary methionine induces alteration in the intestinal microbiome. The composition of the intestinal microbiota is a determinant of health and we, therefore, hypothesized that dietary methionine restriction would also induce changes in the murine microbiome. After one month on a methionine-restricted diet, five-month-old male and female C57BL/6 mice had decreased levels of serum methionine, without changes in body weight. We identified a decrease in the hepatic methylation status of animals fed a methionine-restricted diet compared to controls. This decrease was not associated with changes in DNA or protein methylation in the liver. In males, we saw an increase in families Bacteroidaceae and Verrucoccaceae (mostly A. mucinophila) and a decrease in Rumminococcaceae in animals fed a methionine-restricted diet compared to controls. In females, Bacteroidales family S24-7 was increased two-fold, while families Bacteroidaceae, Verrucoccaceae, Rumminococcaceae, and Rikenellaceae were decreased compared to controls. In summary, feeding a methionine-restricted diet for one month was associated with significant and sex-specific changes in the intestinal microbiome.


2011 ◽  
Vol 50 (11) ◽  
pp. 6638-6645 ◽  
Author(s):  
Namguk Her ◽  
Jong-Sung Park ◽  
Jaekyung Yoon ◽  
Jinsik Sohn ◽  
Sangho Lee ◽  
...  

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
K. M. Sujan ◽  
E. Haque ◽  
M. S. Rakib ◽  
M. I. Haque ◽  
A. Mustari ◽  
...  

Background: Bisphenol-A [BPA, 2, 2-bis (hydroxyphenyl) propane] is widely used in the manufacture of polycarbonate plastic, water bottles, feeders , baby bottles, epoxy resins and inside coating in metallic food cans. Black seed oil (BSO) (Nigella sativa) commonly known as black cumin, reported to be beneficial in function of various systems in the body. The study was carried out to investigate the effect of BPA and BSO on body weight, lipid profile and serum glucose in male and female mice. Methods : A total of thirty (15 male and 15 female) Swiss Albino mice (Mus musculus), aged 25-28 days with an average body weight of 27.4±1g were randomly divided into 3 groups consisting 5 mice in each for each sex. Group A served as vehicle control. Group B was administered BPA @ 50 mg/kg bw daily, while group C received both BPA @ 50 mg/kg/day and BSO @ 1ml/kg/day respectively. Results: Data revealed that BPA treated mice showed slight increase in body weight gain while BSO controlled the weight gain in BPA treated mice. Cholesterol and LDL values were significantly (p<0.01) increased and Triglycerides value was significantly (p<0.01) decreased in BPA-treated mice without significant alterations in HDL value. BPA & BSO treated female mice showed significant (p<0.01) decreased in cholesterol, triglycerides and LDL values. BPA reduced the blood glucose level and addition of BSO had synergistic effects of glucose utilization. Conclusions: It can be concluded that BPA is one of the potential risk factors for hyperlipidemia and obesity. These harmful effects could be alleviated by the ingestion of black seed oil.


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