Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Andriana, Bibin Bintang; Tay, Tat Wei; Tachiwana, Tsuyoshi; Satô, Takeshi; Ishii, Masako; Awal, Mohammad Abdul; Kanai‐Azuma, Masami; Kurohmaru, Masamichi; Hayashi, Yoshihiro

doi:10.2535/ofaj.80.127

Cited by 10 publications

(6 citation statements)

References 20 publications

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“…This prompted us to focus our attention to the primary effects of MEHP on Sertoli cells. Because determining a suitable MEHP concentration to use in the in vitro system and finding a logical correlation with the in vivo system were difficult, we concluded to use a 1 nmol/ml MEHP (low-dose) and 100 nmol/ml MEHP (high-dose) concentration based on findings from other researchers (Andriana et al 2004a, 2004b), who found significant damage to the Sertoli cells of rats and goats after MEHP exposure in vitro.…”

Section: Discussionmentioning

confidence: 99%

Disappearance of Vimentin in Sertoli Cells: A Mono(2-ethylhexyl) Phthalate Effect

et al. 2007

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The effects of mono(2-ethylhexyl) phthalate (MEHP) on 21-day-old C57Bl/6N mice and their Sertoli cell cultures were studied. Mice were given a single dose of 800 mg/kg MEHP by oral gavage and sacrificed 24 h later. At the same time, testes were harvested from another batch of mice for Sertoli cell cultures. Cultures were subsequently exposed to 0, 1, and 100 nmol/ml MEHP for 0, 3, 6, 12, and 24 h. An antivimentin antibody was used to detect intermediate filament changes in Sertoli cells. Meanwhile, detection of preapoptotic signals and presence of apoptotic cells were done using annexin V-FITC (fluorescein isothiocyanate) and TUNEL (deoxynucleotidyltransferase-mediated dUTP nick end labeling) analyses, respectively. In vivo results showed a correlation between the increase in TUNEL-positive cells and the vimentin disruption in treated mice. Toluidine blue staining of the Sertoli cell cultures showed the increased number and size of vacuoles in Sertoli cell cytoplasm. Vimentin immunohistochemistry showed gradual disappearance of vimentin in Sertoli cell cultures as time and dose increased. Some Sertoli cells were found to be annexin V-FITC positive, but no TUNEL-positive cells were found. Taken together, these results show that the appearance of vacuoles and the vimentin disappearance caused by MEHP in the Sertoli cells are related with each other and can be observed in relation to time. This can be used as an indicator of the loss of mechanical support for spermatogenic cells, which in the end causes apoptosis of spermatogenic cells.

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Section: Discussionmentioning

confidence: 99%

Disappearance of Vimentin in Sertoli Cells: A Mono(2-ethylhexyl) Phthalate Effect

et al. 2007

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“…Loss of testicular function is caused by various mechanisms such as antiandrogenic effects of phthalate esters in rats [10] and fish [11], disruption of microtubule dynamics by Sertoli cell toxicants [12][13][14][15][16], disruption of Ca 2+ homeostasis [17], disruption of the blood-testis barrier via the mitogen-activated protein kinase signaling pathway The affected genes were classified into 12 functional categories according to "Gene Ontology".…”

Section: Discussionmentioning

confidence: 99%

“…The present study demonstrated the disruption of all stages of spermatogenesis predicted by histopathological alterations in 3-month-old transgenic rats. These disorders were marked in terms of seminiferous epithelial sloughing, vacuolization and degeneration in spermatocytes in addition to abnormal elongated spermatids and spermatozoa in the seminiferous lumen.cDNA microarray and realtime PCR analyses revealed that the expression levels of four genes (cnot7, fgf7, testin and ostf1) significantly increased (P<0.05) and that those of two genes (versican and mamdc1) decreased (P<0.05).Loss of testicular function is caused by various mechanisms such as antiandrogenic effects of phthalate esters in rats [10] and fish [11], disruption of microtubule dynamics by Sertoli cell toxicants [12][13][14][15][16], disruption of Ca 2+ homeostasis [17], disruption of the blood-testis barrier via the mitogen-activated protein kinase signaling pathway In the epididymides of the transgenic rat, degenerating round spermatids (B1) and many types of abnormal elongated spermatids (B2-4) were frequently observed. Abnormal spermatozoa showing a breakage of surface membranes (B5) and decline in the member of outer dense fiber were also observed (B-6).…”

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confidence: 99%

Accumulated HSV1-TK Proteins Interfere with Spermatogenesis through a Disruption of the Integrity of Sertoli-Germ Cell Junctions

Katō

Chen

et al. 2012

Journal of Reproduction and Development

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Abstract. Transgenic rats show spermatid-specific ectopic expression of the reporter gene, herpes simplex virus type1 thymidine kinase (HSV1-TK), in the testes and have demonstrated male infertility. However, the disruption of spermatogenesis and the underlying molecular mechanisms in these transgenic animals have not been well clarified. In this study, light and electron microscopic observations were performed to characterize the morphological changes in the testes. To explore the molecular mechanisms of male infertility in the HSV1-TK transgenic rat, cDNA microarray and quantitative real-time PCR analyses were performed. The seminiferous tubules of 3-month-old transgenic rats showed morphological alterations including seminiferous epithelial sloughing, vacuolization, and degeneration of spermatogenic cells, suggesting a failure of Sertoli-germ cell interaction. Components of the epididymal lumen from transgenic rats included abnormal spermatozoa, degenerating round spermatids and abnormal elongated spermatids indicating an appearance of direct impairment of spermiogenesis. cDNA microarray and real-time PCRanalyses revealed significant changes (P<0.05) in the gene expression level in six genes, testin, versican, mamdc1, fgf7, ostf1 and cnot7. Among them, testin drew most of our attention, since the testin gene is a sensitive marker for disruption of Sertoli-germ cell adhesion. Thus, our results suggest that the accumulation of HSV1-TK in the spermatids not only directly interferes with spermiogenesis but also disrupts spermatogenesis through a disruption of Sertoligerm cell adhesions. It is important to explore the testicular actions of the HSV1-TK protein in transgenic experimental models and thereby gain clues to find an appropriate treatment for HSV-infected patients exhibiting human male infertility, as has been recently observed. Key words: HSV1-TK, Infertility, Spermatogenesis, Testin, Transgenic rat (J. Reprod. Dev. 58: [544][545][546][547][548][549][550][551] 2012) A suicide gene system, herpes simplex virus type 1 thymidine kinase (HSV1-TK) and its specific substrate, ganciclovir, is widely used for cancer therapy [1,2]. However, previous investigators also reported that HSV1-TK proteins are likely to play a toxic role in the developing mouse male germ cells in the absence of the nucleoside analog, ganciclovir, to induce defects in cell proliferation [3][4][5][6]. The major histological defects of HSV1-TK transgenic mice appeared to be an abnormal nuclear morphology of elongating spermatids and electron microscopy observation disclosed insufficient chromatin condensation and abnormal acrosome structures [4]. Al-Shawi et al. demonstrated that truncated TK polypeptides are translated mainly in the haploid spermatids by a cryptic TATA box-independent promoter and that the severity of male infertility depended on the level of enzymatic activity of HSV1-TK produced [5]. However, precise morphological analyses of the seminiferous tubules of HSV1-TK transgenic mice have not yet been reported.We previously ...

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“…All these chemicals were obtained from Fluka AG, Bucha, SG. Polymerization was accomplished in oven at 60 Cº for 48 hours [4].…”

Section: -Electron Microscopymentioning

confidence: 99%

The Protective Effect of Omega-3 Oil against Cadmium Chloride Induced Nephrotoxicity in Rat

Ismail¹,

Aziz²

2017

Cihan Univ.-Erbil Sci. J.

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The present study was designed to investigate the effect of cadmium (Cd), as cadmium chloride (CdCl2), on the kidney of male rats as well as the protective role of omega-3 oil against the Cd-induced histological, ultrastructural and immunohistochemical alterations. Thirty adult male rats were used in the present work, divided randomly into five groups, six rats in each. The first group was considered as control group and left without treatment except the standard rat chow and tap water. The second group was given (40 mg/ L) of CdCl2 in drinking water. The third group was given (60 mg/ L) of CdCl2 in drinking water. The fourth group was given (40 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet) and the fifth group was given (60 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet). All the above groups were left for 30days. Paraffin and plastic embedded methods were employed for the light microscopy study of the kidney in all treated animals and Immunohistochemical technique was applied to demonstrate apoptosis indicator protein (P53).Transmission electron microscopy preparations was employed for detection of further ultrastructural results. Kidney of CdCl2 treated groups has showed many histological change. These changes included dilation of the kidney tubules, degeneration of the cortical kidney tubule cells and the appearance of inflammatory leucocytes. Such changes have not been seen in the omega-3 plus both doses of CdCl2 groups. The transmission electron microscopy showed many ultrastructural changes, some of them were dilation of the vessels, highly affected podocytes, thickening of the basal lamina of the blood capillaries, lipid accumulation, degeneration of the microvilli of some proximal convoluted tubule cells and disruption of mitochondrial cristae.

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Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Cited by 10 publications

References 20 publications

Disappearance of Vimentin in Sertoli Cells: A Mono(2-ethylhexyl) Phthalate Effect

Disappearance of Vimentin in Sertoli Cells: A Mono(2-ethylhexyl) Phthalate Effect

Accumulated HSV1-TK Proteins Interfere with Spermatogenesis through a Disruption of the Integrity of Sertoli-Germ Cell Junctions

The Protective Effect of Omega-3 Oil against Cadmium Chloride Induced Nephrotoxicity in Rat

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