scholarly journals Bisphenol A Disrupts HNF4α-Regulated Gene Networks Linking to Prostate Preneoplasia and Immune Disruption in Noble Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 207-219 ◽  
Author(s):  
Hung-Ming Lam ◽  
Shuk-Mei Ho ◽  
Jing Chen ◽  
Mario Medvedovic ◽  
Neville Ngai Chung Tam
Keyword(s):  
Bisphenol A ◽  
Gene Networks ◽  
Intraepithelial Neoplasia ◽  
High Dose ◽  
Low Grade ◽  
Treatment Groups ◽  
Adult Rat ◽  
Genome Wide ◽  
17Β Estradiol ◽  
Rat Prostate

Abstract Exposure of humans to bisphenol A (BPA) is widespread and continuous. The effects of protracted exposure to BPA on the adult prostate have not been studied. We subjected Noble rats to 32 weeks of BPA (low or high dose) or 17β-estradiol (E2) in conjunction with T replenishment. T treatment alone or untreated groups were used as controls. Circulating T levels were maintained within the physiological range in all treatment groups, whereas the levels of free BPA were elevated in the groups treated with T+low BPA (1.06 ± 0.05 ng/mL, P < .05) and T+high BPA (10.37 ± 0.43 ng/mL, P < .01) when compared with those in both controls (0.1 ± 0.05 ng/mL). Prostatic hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN), and marked infiltration of CD4+ and CD8+ T cells into the PIN epithelium (P < .05) were observed in the lateral prostates (LPs) of T+low/high BPA-treated rats. In contrast, only hyperplasia and high-grade PIN, but no aberrant immune responses, were found in the T+E2-treated LPs. Genome-wide transcriptome analysis in LPs identified differential changes between T+BPA vs T+E2 treatment. Expression of multiple genes in the regulatory network controlled by hepatocyte nuclear factor 4α was perturbed by the T+BPA but not by the T+E2 exposure. Collectively these findings suggest that the adult rat prostate, under a physiologically relevant T environment, is susceptible to BPA-induced transcriptomic reprogramming, immune disruption, and aberrant growth dysregulation in a manner distinct from those caused by E2. They are more relevant to our recent report of higher urinary levels BPA found in patients with prostate cancer than those with benign disease.

Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake

2002 ◽  
Vol 282 (5) ◽  
pp. E1139-E1146 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Glucose Uptake ◽  
Glycogen Content ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Transporter Protein ◽  
Glut4 Expression ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

This study examined the roles of the female sex steroids, 17β-estradiol (E2) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E2 (E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E2 (P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-μCi injection (ip) of 2-deoxy-[14C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased ( P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher ( P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased ( P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E2 had no effect on GLUT4 protein.

scholarly journals Epigenomic and transcriptomic differences between low-grade and acute inflammation in LPS-induced murine immune cells

2021 ◽  
Author(s):  
Lynette B Naler ◽  
Yuan-Pang Hsieh ◽  
Shuo Geng ◽  
Zirui Zhou ◽  
Liwu Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Inflammation ◽  
Low Dose ◽  
Western Society ◽  
Interferon Response ◽  
High Dose ◽  
Low Grade ◽  
Murine Bone Marrow ◽  
Genome Wide ◽  
Low Grade Inflammation

Chronic, low-grade inflammation has a widespread and significant impact on health, especially in Western society. While inflammation is beneficial for the removal of microbes, low-grade inflammation never resolves and can cause or worsen other diseases. The process by which low-grade inflammation occurs remains poorly understood. Here we exposed murine bone-marrow derived monocytes to chronic lipopolysaccharide (LPS) stimulation at low dose or high dose, as well as a PBS control. The cells were profiled for genome-wide H3K27ac modification and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient monocytes with LPS exposure was also analyzed. We discover that low-grade inflammation preferentially utilizes the TRAM/TRIF-dependent pathway of TLR4 signaling, and induces the expression of interferon response genes. In contrast, acute inflammation uniquely upregulates metabolic and proliferative pathways that also appear to be TRAM-dependent. The extensive differences in the epigenomic landscape between low-dose and high-dose conditions suggest the importance of epigenetic regulations in driving differential responses. Our data provide potential targets for future mechanistic or therapeutic studies.

Short-Term and Long-Term Effects of Bisphenol A (BPA) Exposure During Breastfeeding on the Biochemical and Endocrine Profiles in Rats

2018 ◽  
Vol 50 (06) ◽  
pp. 491-503 ◽  
Author(s):  
Ana Santos-Silva ◽  
Egberto de Moura ◽  
Cintia Pinheiro ◽  
Elaine Oliveira ◽  
Patricia Lisboa
Keyword(s):  
Bisphenol A ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Long Term Effects ◽  
Adult Rat ◽  
Endocrine Profiles ◽  
And Control

AbstractNeonates can be exposed to bisphenol A (BPA) through placenta and milk, and BPA is associated with disorders such as precocious puberty and obesity. We evaluated the effects of BPA exposure during breastfeeding on the biochemical and endocrine profiles in young and adult rat progeny. From postnatal day (PND) 3 to 15 dams were divided into low-dose BPA treatment [50 μg/kg/day s.c. (BPA-LD)], high-dose BPA treatment [5 mg/kg/day s.c. (BPA-HD)], and Control (vehicle) groups. Milk was collected at PND15 and 21, which represents the end of exposure and 6 days after withdrawal, respectively. Dams were euthanized at weaning. Offspring of both genders were euthanized at PND15, 21, and 180. Milk estradiol levels were lower in the BPA-HD group than in the control group at PND 15; however, they were higher at PND21. Female rats whose mothers were BPA-exposed showed more significant differences from those in the control group, including better glycemic control and lipid profiles and higher food intake without higher adiposity, in adulthood than in the weaning period, when they presented with higher adiposity and hyperestrogenism. Conversely, male rats showed more abnormalities after BPA exposure compared to control rats, including insulin, leptin, testosterone, and thyroid hormone changes, when young but exhibited fewer alterations in adulthood, with increase only in LDLc in the BPA-HD rats. Taken together, the present findings suggest that exposure to BPA exclusively through milk affects adiposity, metabolism, and/or hormones of offspring in the short and long term, possibly compromising normal development in both sexes.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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