scholarly journals Decreased Capacity for Sperm Production Induced by Perinatal Bisphenol A Exposure Is Associated with an Increased Inflammatory Response in the Offspring of C57BL/6 Male Mice

2018 ◽  
Vol 15 (10) ◽  
pp. 2158 ◽  
Author(s):  
Yuan Meng ◽  
Ren Lin ◽  
Fengjuan Wu ◽  
Qi Sun ◽  
Lihong Jia
Keyword(s):  
Drinking Water ◽  
Inflammatory Response ◽  
Bisphenol A ◽  
Protein Expression ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Male Offspring ◽  
Perinatal Exposure ◽  
Sperm Production ◽  
Tnf Α

Many previous studies have indicated the adverse effects of bisphenol A (BPA) on sperm production and quality; however, the mechanisms underlying BPA male reproductive toxicity have yet to be elucidated. The main purpose of this study was to investigate the effect of perinatal exposure to BPA on the spermatogenic capacity of male offspring, and to explore the possible influence of inflammatory responses in BPA reproductive toxicity. Twenty-one pregnant C57BL/6mice were randomly divided into three groups: a control group, a group receiving 0.2 μg/mL (LBPA), and a group receiving 2 μg/mL of BPA (HBPA), all via drinking water from gestational day 6 to the end of lactation. After weaning, one male mouse was randomly selected from each group (n = 7/group); these three mice were fed a normal diet and drinking water for 1 month. Levels of serum testosterone (T) and tumor necrosis factor (TNF)-α were then measured in all mice. Sperm count and the proportion of sperm malformation were also determined. The levels of Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, and aryl hydrocarbon receptor (AhR) protein expression in the testis tissue were determined. Analysis showed that the proportion of sperm malformation increased in the LBPA and HBPA groups (p < 0.05). Sperm count significantly decreased only in the HBPA group (p < 0.05), while the levels of serum TNF-α increased in the LBPA and HBPA groups (p < 0.05). Levels of serum T decreased significantly in the HBPA group, compared with controls (p < 0.05). Levels of TLR4 and NF-κB protein expression in the testis were significantly higher in the LBPA and HBPA groups (p < 0.05 or p < 0.01), while AhR protein expression was higher and seminiferous tubules in the testis showed more damage in the HBPA group compared to controls (p < 0.05 and p < 0.01, respectively). Our results showed that perinatal exposure to low or high doses of BPA decreased the capacity for spermatogenesis in male offspring, which may be associated with an inflammatory response activated by the TLR4/ NF-κB and AhR signaling pathways in the testis.

Male reproductive toxicity of sodium arsenite in mice

2004 ◽  
Vol 23 (8) ◽  
pp. 399-403 ◽  
Author(s):  
Niraj Pant ◽  
R C Murthy ◽  
S P Srivastava
Keyword(s):  
Drinking Water ◽  
Sodium Arsenite ◽  
Sperm Count ◽  
Prostate Gland ◽  
Reproductive Toxicity ◽  
Atomic Absorption Spectrophotometry ◽  
Reproductive Organs ◽  
Oral Exposure ◽  
Human Beings ◽  
Testicular Weight

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 βmol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17β-hydroxysteroid dehydrogenase (17β-HSD) were significantly decreased, but those of lactate dehydrogenase and γ-glutamyl transpeptidase (γ-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 μmol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.

scholarly journals Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

2018 ◽  
Vol 49 (2) ◽  
pp. 610-625 ◽  
Author(s):  
Chun-Yan He ◽  
Li-Peng Jiang ◽  
Cheng-Yue Wang ◽  
Yue Zhang
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Pyrrolidine Dithiocarbamate ◽  
Mrna Levels ◽  
Periodontal Ligament Fibroblasts ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Tnf Α

Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

666: Maternal bisphenol a (BPA) exposure programs male offspring hepatic insulin signaling protein expression

2015 ◽  
Vol 212 (1) ◽  
pp. S327-S328
Author(s):  
Kristina Galyon ◽  
Farnoosh Farshidi ◽  
Michael Ross ◽  
Mina Desai ◽  
Juanita Jellyman
Keyword(s):  
Bisphenol A ◽  
Protein Expression ◽  
Insulin Signaling ◽  
Male Offspring ◽  
Signaling Protein ◽  
Hepatic Insulin Signaling

scholarly journals Angiotensin II AT1 blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen

2009 ◽  
Vol 296 (5) ◽  
pp. R1376-R1384 ◽  
Author(s):  
Enrique Sánchez-Lemus ◽  
Julius Benicky ◽  
Jaroslav Pavel ◽  
Ignacio M. Larrayoz ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Bacterial Endotoxin ◽  
Ang Ii ◽  
Tnf Α ◽  
Mrna And Protein Expression

ANG II AT1 receptor blockade reduces inflammation in hypertension. To determine whether ANG II AT1 receptor blockers (ARBs) influence the innate immune inflammatory response in normotensive rats, we studied rat plasma and spleen after a 3-day subcutaneous pretreatment with the ARB candesartan followed by a single dose of the bacterial endotoxin LPS (50 μg/kg ip). Peripheral administration of LPS to rodents produced a generalized inflammatory response with increased release of TNF-α, IL-1β, and IL-6 into the circulation. Candesartan pretreatment reduced the LPS-induced release of TNF-α, IL-1β, and IL-6 into the circulation. The red pulp of rat spleen expressed large numbers of AT1 receptors and the LPS receptors Toll-like receptor 4 and CD14. Candesartan administration significantly blocked AT1 receptors. The ARB reduced the LPS-induced upregulation of CD14 gene expression; expression of TNF-α and IL-6 mRNA and protein; expression of IL-1β and IκB-α mRNA; COX-2 mRNA and protein expression and PGE2 concentration; inducible nitric oxide synthase (iNOS) gene and protein expression and iNOS activity; and Nox2 gene expression and 8-isoprostane levels. In addition, candesartan reduced the CD14 protein expression in saline- and LPS-treated rats. Our results suggest that AT1 receptors are essential for the development of the full innate immune response to bacterial endotoxin. The ARB decreased the general peripheral inflammatory reaction to LPS and partially decreased the inflammatory response in the spleen. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that ARBs may have therapeutic effects on inflammatory conditions.

scholarly journals Supervillin contributes to LPS-induced inflammatory response in THP-1 cell-derived macrophages

2021 ◽  
Author(s):  
Jun Zhou ◽  
Yuhui Que ◽  
Lihua Pan ◽  
Xu Li ◽  
Chao Zhu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Actin Binding ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Underlying Mechanisms

Abstract Supervillin (SVIL), the largest member of villin/gelsolin family, is an actin-binding and membrane-associated protein, that can also be localized to the nucleus. It has been reported that the mRNA expression of SVIL in neutrophils could be increased by lipopolysaccharide (LPS), but the underlying mechanisms remain unknown. Moreover, SVIL was also observed to be involved in the regulation of macrophages’ movement. However, it is not clear whether SVIL is involved in the LPS-induced inflammatory response in macrophages. This work was to investigate the underlying molecular mechanisms of LPS regulating SVIL expression in macrophages and hence the possible role of SVIL in LPS-induced inflammation. Our data showed that in THP-1-derived macrophages, LPS stimulation significantly increased SVIL mRNA and protein expression. Inhibition of TLR4 by Resatorvid (Res) completely reversed the expression of SVIL and inflammatory cytokines (IL-6, IL-1β and TNF-α) induced by LPS. Additionally, ERK1/2 and NF-κB inhibitors (U0126 and BAY) significantly reduced SVIL and IL-6, IL-1β & TNF-α expression. Furthermore, down-regulation of SVIL by SVIL-specific shRNA significantly attenuated the expression of IL-6, IL-1β & TNF-α induced by LPS. Taken together, as a downstream molecule of TLR4/NF-κB and ERK1/2, SVIL was involved in the inflammatory response of LPS-induced elevated IL-6, IL-1β and TNF-α in macrophages.

USP15 alleviates the cerulein-induced cell apoptosis and inflammatory injury to AR42J cells through regulating TAB2/3/NF-κB pathway in acute pancreatitis

2021 ◽  
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Parenchymal Cell ◽  
Over Expression ◽  
Tnf Α

Acute pancreatitis, characterized by parenchymal cell death and inflammatory process of pancreas, is a lethal disease. USP15 (ubiquitin-specific peptidase 15) belongs to USP family and participates in the ubiquitination system. USP15 was implicated in inflammatory processes and involved in the tumor progression. However, the roles of USP15 in acute pancreatitis-associated inflammation and apoptosis have not been reported yet. Firstly, in vitro cell model of acute pancreatitis was established through incubation of AR42J with cerulein. Results showed that cerulein induced inflammatory response in AR42J with up-regulation of TNF-α, IL-6 and IL-1β. USP15 was up-regulated in cerulein-induced AR42J. Secondly, siRNA-mediated silence of USP15 reduced levels of TNF-α, IL-6 and IL-1β, and pcDNA-mediated over-expression of USP15 enhanced the levels of TNF-α, IL-6 and IL-1β. Moreover, cell apoptosis of cerulein-induced AR42J was suppressed by silence of USP15 with reduced cleaved caspase-3 and cleaved caspase-9, while promoted by USP15 over-expression. Lastly, silence of USP15 decreased protein expression of p65 phosphorylation and TAB (Transforming growth factor-β activated kinase-1 binding protein) 2/3 in cerulein-induced AR42J, while the protein expression was enhanced by USP15 over-expression. In conclusion, USP15 contributed to cerulein-induced AR42J inflammatory response and cells injury through regulation of TAB2/3/NF-κB pathway in acute pancreatitis.

scholarly journals Two-Generation Reproduction Study and Immunotoxicity Screen in Rats Dosed with Phenol via the Drinking Water

2001 ◽  
Vol 20 (3) ◽  
pp. 121-142 ◽  
Author(s):  
B. M. Ryan ◽  
R. Selby ◽  
R. Gingell ◽  
J. M. Waechter ◽  
J. H. Butala ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Sperm Count ◽  
Body Weight Gain ◽  
Reproductive Toxicity ◽  
Plaque Assay ◽  
Daily Intake ◽  
Histological Evaluation ◽  
Male Reproductive Function ◽  
Reproduction Study

This study evaluated the potential reproductive toxicity of phenol in a rat two-generation reproduction study, which included additional study endpoints, such as sperm count and motility, developmental landmarks, histological evaluation of suspect target organs (liver, kidneys, spleen, and thymus), weanling reproductive organ weights, and an immunotoxicity screening plaque assay. Phenol was administered to 30 Sprague-Dawley rats/sex/group in the drinking water at concentrations of 0, 200, 1000, or 5000 ppm. Parental (P1) animals were treated for 10 weeks prior to mating, during mating, gestation, lactation, and until sacrifice. The F1 generation (P1 offspring) was treated using a similar regimen, while the F2 generation was not treated. After mating, 10 P1 males/group were evaluated using standard clinical pathology parameters and an immunotoxicity screening plaque assay. Significant reductions in water and food consumption were observed in the 5000-ppm group in both generations; corollary reductions in body weight/body weight gain were also observed. Mating performance and fertility in both generations were similar to controls, and no adverse effects on vaginal cytology or male reproductive function were observed. Vaginal opening and preputial separation were delayed in the 5000-ppm group, and were considered to be secondary to the reduction in F1 body weight. Litter survival of both generations was reduced in the 5000-ppm group. Absolute uterus and prostate weights were decreased in the F1 generation at all dose levels; however, no underlying pathology was observed and there was no functional deficit in reproductive performance. Therefore, these findings were not considered to be adverse. No evidence of immunotoxicity was noted in the 5000-ppm group. The effects noted at the high concentration were presumed to be associated with flavor aversion to phenol in the drinking water. Based on a comprehensive examination of all parameters, the no-observable-adverse-effect level (NOAEL) for reproductive toxicity of phenol administered in drinking water to rats is 1000 ppm. The corresponding daily intake of phenol for an adult rat at the NOAEL of 1000 ppm is equivalent to about 70 mg/kg/day for males and 93 mg/kg/day for females.

Perinatal exposure to a low dose of bisphenol-A advances pubertal spermatogenesis of F1 adolescent male rats

2020 ◽  
Author(s):  
Yinyang Bai ◽  
Fang Xiong ◽  
Yun Zhang ◽  
Jie Chen ◽  
Lishuang Xu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Plasma Levels ◽  
Low Dose ◽  
Male Offspring ◽  
Female Rats ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Perinatal Exposure ◽  
Significant Difference ◽  
The Impact

Abstract Background To investigate the impact of perinatal exposure to a low dose of bisphenol A (BPA) on spermatogenesis in male rats and the underlying mechanism. Methods Female rats were injected subcutaneously with 2 µg BPA/kg/day from gestation day 10 through lactation day 7. The spermatogenesis and expression of key regulatory genes in the testes as well as the central modulators of the hypothalamic-pituitary-gonadal axis were determined in male offspring on postnatal day 18, 21, and 24 (PND18, 21, and 24). Results 1) Perinatal BPA exposure led to an increase in the weight of body and testis in PND21-24 male offspring. The seminiferous tubular diameter and the number of round spermatids were significantly increased in PND21 BPA-rats, while the volumes of the Sertoli cells, spermatogonia and spermatocytes were not significantly altered. 2) Compared to the control rats, the expression levels of key meiotic regulators such as cyclinA1, c-jun and c-fos in the seminiferous tubules were significantly elevated in PND21 BPA-rats. 3) The plasma levels of FSH and LH (PND21 and PND24) as well as the frequency of pulsatile LH secretion (PND21) were significantly increased in BPA-rats, although the plasma levels of testosterone and estrogen showed no significant difference between the two groups. 4) In comparison with control rats, the levels of GnRH mRNA in the preoptic area (POA) and kiss1 mRNA in arcuate nucleus (ARC) were significantly increased in the BPA-rats, whereas the level of ERα mRNA in ARC was decreased, although the number of GnRH-positive cells and ARC kisspeptin-positive cells were unchanged. Interestingly, neither the number of kisspeptin-positive cells nor the level of kiss1 mRNA in the anteroventral periventricular nucleus (AVPV) showed a difference between the two groups. Conclusion Perinatal exposed to a low dose of BPA leads to an increased meiosis of spermatocytes and promotes the spermatogenesis in male offspring, most likely through activation of the hypothalamic-pituitary-gonadal axis.

scholarly journals Environmental Pollution as a Risk Factor in Testicular Tumour Development: Focus on the Interaction between Bisphenol A and the Associated Immune Response

2019 ◽  
Vol 16 (21) ◽  
pp. 4113 ◽  
Author(s):  
Karen Elizabeth Nava-Castro ◽  
Ricardo Ramírez-Nieto ◽  
Lucía Angélica Méndez-García ◽  
Manuel Iván Girón-Pérez ◽  
Mariana Segovia-Mendoza ◽  
...  
Keyword(s):  
Immune Response ◽  
Bisphenol A ◽  
Tumour Growth ◽  
Immune Cell ◽  
Breast Cancer Incidence ◽  
Pregnant Female ◽  
Male Offspring ◽  
Testicular Tumour ◽  
Female Mice ◽  
Tnf Α

Bisphenol A (BPA) is an endocrine disruptor to which animals and humans are highly exposed. Many reports have established a relationship between BPA exposure and breast cancer incidence, especially during critical periods of development. However, its effects on the immune response in testicular tumour growth have not yet been described. Thus, we wanted to analyse the effect of perinatal BPA exposure in pregnant female mice and the immune response modulation and tumour growth in an intratesticular cancer model in offspring male mice. Pregnant female mice were exposed to a dose of 250 mg/kg/day/body weight of BPA in their drinking water. In adulthood, male offspring underwent intrascrotal inoculation with 4T1 cancer cells. On day 21 after inoculation, mice were euthanised, and serum was obtained to measure BPA levels using HPLC coupled to mass spectrometry. The percentages of immune cell populations in peripheral lymph nodes (PLN), the spleen and tumours were evaluated by flow cytometry. In addition, the tumour expression of IL-10, TNF-α and TGF-β was analysed by RT-PCR. Of note, we found detectable circulating levels of BPA in the offspring of mothers exposed to it while pregnant. Remarkably, BPA treatment promoted tumour growth by about 75% compared to mice coming from female mice that did not receive the compound. Perinatal exposure to BPA modulated the percentages of different immune cells in the spleen and PLN. In addition, the expression of inflammatory-related cytokines (IL-10 and TNF-α) in the tumours was significantly enhanced compared to control and vehicle groups. In conclusion, the perinatal BPA administration in pregnant female mice modulated different cellular and molecular immune components that resulted in outstanding testicular tumour size in male offspring.

Perinatal exposure of rats to Bisphenol A affects fertility of male offspring—An overview

2011 ◽  
Vol 31 (3) ◽  
pp. 359-362 ◽  
Author(s):  
Smita Salian ◽  
Tanvi Doshi ◽  
Geeta Vanage
Keyword(s):  
Bisphenol A ◽  
Male Offspring ◽  
Perinatal Exposure
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