The effects of mono-2-ethylhexyl phathalate, adriamycin and N-ethyl-N-nitrosourea on stage-specific apoptosis and DNA synthesis in the mouse spermatogenesis

Suominen, J.; Linderborg, Jussi; Nikula, Hannu; Hakovirta, Harri; Parvinen, Martti; Toppari, Jorma

doi:10.1016/s0378-4274(03)00170-x

Cited by 39 publications

(21 citation statements)

References 36 publications

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“…DXR has been shown to adversely affect spermatogenesis as well as the quantity and quality of sperm; it exerts its toxicity via oxidative stress pathways (Sikka 1996, Suominen et al 2003, Hou et al 2005, Ateşşahin et al 2006. Previous studies have demonstrated that the level of malondialdehyde (MDA), which derives from lipid peroxidation, rises after exposure to DXR, whereas the level of GSH declines (Quiles et al 2002, Ateşşahin et al 2006.…”

Section: Discussionmentioning

confidence: 99%

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Levi¹,

Tzabari²,

Savion³

et al. 2015

Reproduction

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Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5 mg/kg DXR, 100 mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. Reproduction (2015) 150 357-366

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Section: Discussionmentioning

confidence: 99%

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Levi¹,

Tzabari²,

Savion³

et al. 2015

Reproduction

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“…We cannot yet explain this observation and, unfortunately, inhibin B levels have not been measured in animal experiments. However, histologic studies of rodent testes exposed pre- and perinatally show vacuolization of Sertoli cells (Borch et al 2004, 2005) and apoptosis of spermatogenic cells in cultures of mouse seminiferous tubules (Suominen et al 2003). …”

Section: Discussionmentioning

confidence: 99%

Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age

Main

Mortensen

Kaleva

et al. 2006

Environ Health Perspect

623

395

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Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.DesignWe obtained biologic samples from a prospective Danish–Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1–3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B.ResultsAll phthalate monoesters were found in breast milk with large variations [medians (minimum–maximum)]: mMP 0.10 (< 0.01–5.53 μg/L), mEP 0.95 (0.07–41.4 μg/L), mBP 9.6 (0.6–10,900 μg/L), mBzP 1.2 (0.2–26 μg/L), mEHP 11 (1.5–1,410 μg/L), miNP 95 (27–469 μg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001–0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21–0.323, p = 0.002–0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = −0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies.ConclusionsOur data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.

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“…Anthracyclins such as adriamycin, a chemical structurally related to DAU, and etoposide, are known to alter male germ cells [16]; moreover, rat A1 spermatogonia have been reported to be highly sensitive to adriamycin [17]. Besides, this chemical increases apoptosis in spermatogonia, as well as in preleptotene, zygotene, and pachytene spermatocytes [18]. In our assay for measuring the induction of SCE in spermatogonial cells, DAU showed a strong effect, similar to that previously reported in bone marrow cells [11].…”

Section: Discussionmentioning

confidence: 99%

Antigenotoxic Effect of Chamomilla recutita (L.) Rauschert Essential Oil in Mouse Spermatogonial Cells, and Determination of Its Antioxidant Capacity in Vitro

Hernández-Ceruelos¹,

Madrigal-Santillán²,

Morales-González³

et al. 2010

IJMS

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Chamomilla recutita (L.) Rauschert (Asteraceae), popularly known as chamomile, is a plant used in traditional medicine for various therapeutic purposes. Chamomile essential oil (CEO) is particularly known to inhibit the genotoxic damage produced by mutagens in mice somatic cells. The aim of this research was to determine the inhibitory potential of CEO on the genotoxic damage produced by daunorubicin (DAU) in mice germ cells. We evaluated the effect of 5, 50, and 500 mg/kg of essential oil on the rate of sister chromatid exchange (SCE) induced in spermatogonia by 10 mg/kg of the mutagen. We found no genotoxicity of CEO, but detected an inhibition of SCE after the damage induced by DAU; from the lowest to the highest dose of CEO we found an inhibition of 47.5%, 61.9%, and 93.5%, respectively. As a possible mechanism of action, the antioxidant capacity of CEO was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method and ferric thiocyanate assays. In the first test we observed a moderate scavenging potential of the oil; nevertheless, the second assay showed an antioxidant capacity similar to that observed with vitamin E. In conclusion, we found that CEO is an efficient chemoprotective agent against the damage induced by DAU in the precursor cells of the germinal line of mice, and that its antioxidant capacity may induce this effect.

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The effects of mono-2-ethylhexyl phathalate, adriamycin and N-ethyl-N-nitrosourea on stage-specific apoptosis and DNA synthesis in the mouse spermatogenesis

Cited by 39 publications

References 36 publications

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age

Antigenotoxic Effect of Chamomilla recutita (L.) Rauschert Essential Oil in Mouse Spermatogonial Cells, and Determination of Its Antioxidant Capacity in Vitro

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