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MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.

ABSTRACT: The testis is an organ that maintains an immune suppressive environment. We previously revealed that exposure of pre-pubertal rats to an acute dose of a well-described Sertoli cell toxicant, mono-(2-ethylhexyl) phthalate (MEHP), leads to an accumulation of CD11b+ immune cells in the testicular interstitial space that closely correlates with a robust incidence of germ cell (GC) apoptosis. Here, we test the hypothesis that the infiltrating immune cells contribute to GC apoptosis. Postnatal day 28 Fischer rats that received an oral dose of 700?mg/kg MEHP showed a significant infiltration of both CD11bc+/CD68+/CD163- macrophages and neutrophils. The infiltration peaked at 12?h, but had reduced by 48?h. Testicular macrophages from MEHP-treated rats showed significantly upregulated expression of Tnfa and Il6, and the Arg1/Nos2 ratio was reduced compared to controls. However, small increases in anti-inflammatory genes Il10 and Tgfb1 were also observed. Depletion of circulating monocytes with clodronate liposomes prior to MEHP treatment reduced the macrophage influx into the testis, but did not lower GC apoptosis. Additionally, depletion of neutrophils using an anti-polymorphonuclear cell antibody prevented both macrophage and neutrophil infiltration into the testis, and also did not affect GC apoptosis. Together, these results show that exposure to MEHP leads to a rapid and temporary influx of pro-inflammatory monocytes and neutrophils in the interstitium of the testis. However, with this acute dosing paradigm, these infiltrating leukocytes do not appear to contribute to MEHP-induced testicular GC apoptosis leaving the functional significance of these infiltrating cells in the pathogenesis of MEHP-induced testicular injury unresolved.

SUBMITTER: Voss JJLP

PROVIDER: S-EPMC6021206 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.

Voss Jorine J L P JJLP Stermer Angela R AR Ghaffari Rashin R Tiwary Richa R Richburg John H JH

Reproduction (Cambridge, England) 20180509 1

The testis is an organ that maintains an immune suppressive environment. We previously revealed that exposure of pre-pubertal rats to an acute dose of a well-described Sertoli cell toxicant, mono-(2-ethylhexyl) phthalate (MEHP), leads to an accumulation of CD11b+ immune cells in the testicular interstitial space that closely correlates with a robust incidence of germ cell (GC) apoptosis. Here, we test the hypothesis that the infiltrating immune cells contribute to GC apoptosis. Postnatal day 28 ...[more]

PMID: 29743262

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Project description:Obesity is a debilitating disorder with a variety of problems including oxidative stress, inflammation, and apoptosis. The aim of our study was to investigate the therapeutic role of bee bread on oxidative stress, apoptosis, and inflammation in the testis of obese rats. Thirty-two adult male Sprague Dawley rats, with weights between 230-300 g, were distributed into four groups (n = 8/group), namely normal control (C), obese (Ob), obese + BB or obese + OR [high-fat diet (HFD) for 6 weeks then HFD plus bee bread or orlistat for another 6 weeks] groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was diluted with distilled water and administered daily for 6 weeks by oral gavage. There were significant decreases in the activities of antioxidant enzymes [glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR)], glutathione (GSH)] and total antioxidant capacity (TAC) levels and mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (Sod), catalase (Cat) and glutathione peroxidase (Gpx) in the obese group relative to the control group. Meanwhile, the mRNA levels of pro-inflammatory markers, namely: inducible nitric oxide synthase (Inos), nuclear factor kappa B (Nf-κβ), tumour necrotic factor α (Tnf-α) and interleukin 1β (Il-1β) were significantly increased while interleukin (Il-10) was decreased in the obese group relative to the control group. Further, proliferating cell nuclear antigen (PCNA) immunoexpressions decreased while cleaved caspase-3 immunohistochemical staining increased significantly in the obese group, in addition to increases in the mRNA levels of p53, Bax, Caspases-8, 9 and 3, relative to the control group. Treatment with bee bread showed increases in antioxidant enzymes and PCNA immunoexpression, as well as decreases in inflammation and apoptosis markers in the testes. This study has shown that bee bread has therapeutic effects against oxidative stress, inflammation, apoptosis in the testis of HFD-induced obese male rats, thereby suggesting its role as a natural supplement capable of treating obesity-induced male reproductive impairment.

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MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.

Publications

MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.

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