Spermatogonial Cytogenetic Toxicity of Vincristine and its Transmission in the Germline Cells of Swiss Mice

Choudhury, Ramesh C.; Das, Biswamitra; Misra, Sunil; Jagdale, M.B.

doi:10.1615/jenvironpatholtoxicoloncol.v21.i3.60

Cited by 6 publications

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“…The present study reports no case of azoospermia in mice treated with CYP at a low gonadotoxic dose and one male displayed azoospermia in VCR group. The decreased sperm count uncovered in VCR-treated mice indicated a VCR toxicity on germ cells, as previously reported in other studies 24,32,33 . The rise in sperm counts observed between D66 and D140 in the VCR group suggests a possible sperm recovery.…”

Section: Discussionsupporting

confidence: 88%

Paradoxical risk of reduced fertility after exposure of prepubertal mice to vincristine or cyclophosphamide at low gonadotoxic doses in humans

Delessard

Saulnier

Dumont

et al. 2020

Sci Rep

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Cancer treatment can have long-term side effects in cured patients and infertility is one of them. Given the urgency of diagnosis in children with cancer, the toxicity of treatments on the gonad was overshadowed for a long time. In the present study, prepubertal mice were treated by vincristine or cyclophosphamide commonly used in acute leukaemia treatment. The prepubertal exposure to cyclophosphamide, at a low gonadotoxic dose in humans (< 3.5 g/m2), led to morphological alterations of prepubertal testicular tissue. An increased proportion of spermatozoa with hypocondensed chromatin and oxidized DNA associated with decreased fertility were uncovered at adulthood. Short- and long-term morphological alterations of the testicular tissue, disturbed progression of spermatogenesis along with increased proportions of isolated flagella and spermatozoa with fragmented DNA were evidenced in vincristine-treated mice. Moreover, the fertility of mice exposed to vincristine was severely affected despite being considered low-risk for fertility in humans. Paternal exposure to vincristine or cyclophosphamide before puberty had no impact on offspring development. Contrary to the current gonadotoxic risk classification, our results using a mouse model show that vincristine and cyclophosphamide (< 3.5 g/m2) present a high gonadotoxic risk when administered before the initiation of spermatogenesis.

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Section: Discussionsupporting

confidence: 88%

Paradoxical risk of reduced fertility after exposure of prepubertal mice to vincristine or cyclophosphamide at low gonadotoxic doses in humans

Delessard

Saulnier

Dumont

et al. 2020

Sci Rep

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“…This study also agrees with other studies (27;23) which reveal that vincristine, Vinorelbine and Vinblastine induced a significant increase in micronuclei (MN) frequencies in binucleated (BN) cell, as well as producing slowing of the cell cycle, causing a decrease in the percentage of BN cells in cultured human lymphocytes and in female CD-1 mice. ( 29).Another study proved the cytotoxic and genotoxic effects of vincristine on germ cells of male mice, vincristine administration resulted in damage to DNA in spermatocytes and spermatids, reduction in the rate of germ cell development, and killing of the non-proliferating spermatid cells (30).…”

Section: D-micronuclei Assaymentioning

confidence: 97%

An Investigation of the Cytotoxic, Cytogenetic and Teratogenic Potentials of Catharanthusroseus

2016

IJSR

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The results revealed that the plant extract showed a significant induction of sperm abnormalities at the three concentrations used comparing with the untreated animals. The administration of a single injection of 0.767gm/kg of C. roseus extract to twenty pregnant females mice on the day 10 through 16 of gestation period did not show any apparent malformations. However, compared with the control population of the pup's number, body length, and head length was significantly reduced within the first day of life. Overall, those finding indicate that Catharanthus roseus aqueous extract can induce significant mitotic inhibition, slight chromosome aberrations and micronuclei frequencies and it can bring about significant percentage of abnormal spermatozoa, besides its ability to cross placental barrier causing some growth retardation; rather than teratogenic effects.

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Immunosuppressants and Male Reproduction

Drobnis

Nangia

2017

Advances in Experimental Medicine and Biology

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Prolonged use of immunosuppressant medications is occasionally seen in infertile men with chronic inflammatory conditions; autoimmune disorders; or an organ or hematopoietic stem cell transplant. Chronic inflammation impacts negatively on male reproductive endpoints, so immunosuppressant therapy can produce improvements. Corticosteroids have been used to treat antisperm antibodies and even as an empirical treatment for male infertility in general. Trials of these methods have provided mixed results on semen quality and fertility, with improvement, no change and negative effects reported by different investigators. In a substantial number of observational studies, patients on long-term therapy with prednisone for chronic inflammatory disease, testosterone levels were lower compared to untreated controls, though randomized controlled trials have not been conducted. Similarly decreases in testosterone have been reported in men receiving corticosteroids to minimize transplant rejection; however, most were treated with multiple immunosuppressive medications that may have contributed to this effect. A large number of trials of healthy men treated with corticosteroids have shown some disruption in reproductive hormone levels, but other studies reported no effect. Studies in monkeys, rats (at human equivalent dose), cattle, sheep, and horses have shown endocrine disruption, including low testosterone with dexamethasone treatment. Of the cytostatic immunosuppressives, which have high potential for cellular damage, cyclophosphamide has received the most attention, sometimes lowering sperm counts significantly. Methotrexate may decrease sperm numbers in humans and has significant negative impacts in rodents. Other chemotherapeutic drugs used as immunosuppressants are likely to impact negatively on male fertility endpoints, but few data have been collected. The TNF-α Inhibitors have also received little experimental attention. There is some evidence that the immunophilin modulators: cyclosporine, sirolimus, and everolimus cause endocrine disruption and semen quality impairment. As we review in this chapter, results in experimental species are concerning, and well-designed studies are lacking for the effects of these medications on reproductive endpoints in men.

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Spermatogonial Cytogenetic Toxicity of Vincristine and its Transmission in the Germline Cells of Swiss Mice

Cited by 6 publications

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Paradoxical risk of reduced fertility after exposure of prepubertal mice to vincristine or cyclophosphamide at low gonadotoxic doses in humans

Paradoxical risk of reduced fertility after exposure of prepubertal mice to vincristine or cyclophosphamide at low gonadotoxic doses in humans

An Investigation of the Cytotoxic, Cytogenetic and Teratogenic Potentials of Catharanthusroseus

Immunosuppressants and Male Reproduction

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