Exposure to Bleomycin, Etoposide, and Cis-Platinum Alters Rat Sperm Chromatin Integrity and Sperm Head Protein Profile1

Maselli, Jennifer; Hales, Barbara F.; Chan, Peter; Robaire, Bernard

doi:10.1095/biolreprod.111.098616

Cited by 38 publications

(41 citation statements)

References 38 publications

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“…Spermadine, the product of SRM, is important in fetal development, stages of spermatogenesis and steroidogenesis (Lefevre et al 2011). HSP90B1 was recently associated with alterations in sperm chromatin integrity following exposure to chemotherapeutic agents (Maselli et al 2012) and found to be predictive of small clusters. Interestingly, while DPYL2 was not correlated with the formation of large Leydig cell clusters, it was predictive of these clusters.…”

Section: Biomarkers Of Dysgenesis In Fetal Rat Testismentioning

confidence: 99%

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Klinefelter¹,

Laskey²,

Winnik³

et al. 2012

Reproduction

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Significant research has been focused on phthalate-induced alterations in male reproductive development. Studies on rodents have prompted the notion that a syndrome exists in the human male which includes phenotypic alterations such as hypospadias, cryptorchidism, poor semen quality, and even testicular cancer. Each phenotype in this 'testicular dysgenesis syndrome' is predicated on reduction in testosterone production by the fetal Leydig cell. We sought to examine the relationship between dysgenesis and steroidogenic capacity in the fetal rat testis more stringently by incorporating lower exposures than those typically used, conducting a comprehensive, non-targeted quantitative evaluation of the fetal testis proteome, and relating alterations in individual proteins to the capacity of the fetal Leydig cell to produce testosterone, and histopathology of the fetal testis. Pregnant dams were dosed orally from gestation day (GD) 13-19 with 0, 10, or 100 mg diethylhexyl phthalate (DEHP)/kg body weight per day. Each endpoint was represented by 16 l. Clustering of Leydig cells occurred before any significant decrease in the capacity of the GD19 Leydig cell to produce testosterone. At 100 mg DEHP/kg, testosterone production was reduced significantly, Leydig cell clusters became quite large, and additional dysgenetic changes were observed in the fetal testis. Of 23 proteins whose expression was altered significantly at both DEHP exposure levels, seven were found to be correlated with and predictive of the quantified endpoints. None of these proteins have been previously implicated with DEHP exposure. Notably, pathway analysis revealed that these seven proteins fit a pathway network in which each is regulated directly or indirectly by estradiol.

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Section: Biomarkers Of Dysgenesis In Fetal Rat Testismentioning

confidence: 99%

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Klinefelter¹,

Laskey²,

Winnik³

et al. 2012

Reproduction

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“…Some testis tumors are treated using cisplatin (Koychev et al, 2011). Recent report analyzed the impact of such treatment on the integrity of spermatozoa chromatin in rats (Maselli et al, 2012). As expected, the cisplatin treatment lead to susceptibility of DNA to denaturation and the number of strand breaks were significantly increased in mature sperm.…”

Section: Epigenetic and Testicular Cancersmentioning

confidence: 99%

Epigenetic: a molecular link between testicular cancer and environmental exposures

Véga¹,

Baptissart²,

Caira³

et al. 2012

Front. Endocrin.

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In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

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“…However, this balance can readily be broken by the chemicals like the CP, that disrupts the prooxidant-antioxidant balance, leading to cellular dysfunction [20] . Also, the CP can induce free radical toxic stress and spermatic DNA damage [21,22] .…”

Section: Introductionmentioning

confidence: 99%

Erkek Ratlarda Maclura pomifera Ekstraktının Sisplatin ile Oluşturulmuş Üreme Sistemi Hasarı Üzerine Etkisi

Aksu¹,

Akman²,

Özkaraca³

et al. 2015

Kafkas Univ Vet Fak Derg

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In this study, we aimed to investigate the effect of maclura pomifera (MP) (known as cytotoxic, anti-tumoural, anti-inflammatoric, antinociceptive, and anti-oxidative) extract upon the spermatological parameters in Cisplatin (anti-tumoural chemotherapeutic with Reactive Oxygen Species (ROS)-generating side-effects)-treated rats. A total of seventeen male Sprague Dawley rats, aged eight weeks and weighing 250-300 g, were used. Three experimental groups were assigned, as follows; Group 1 (n=5) as control (C): the animals received intraperitoneal (IP) injection of physiological saline and further saline via oral gavage during 5 days before and after the injection, Group 2 (n=6): single IP injection of 7 mg/kg Cisplatin (CP) and saline via oral gavage as above, and Group 3 (n=6): referred as MP + CP, oral administration of 500 mg/kg/day MP extract during 5 days before and after cisplatin (CP) injection, as above. At the end of the experiment, rats were decapitated and their testes and cauda epididymis weights as well as epididymal sperm parameters were analysed. The CP administration caused a significant (P<0.05) decline in sperm motility and density, with a significant increase in dead spermatozoa. The MP + CP combination also led to a significant decline (P<0.05) in the weights of total cauda epididymis and of testes, but significantly improved (P<0.05) sperm survival as compared to the CP alone. In conclusion; the findings suggested that the MP plus CP combination had an adverse effect upon the total weights of testes and cauda epididymis, however the dead sperm rate was markedly lower than the CP alone. Keywords: Cisplatin, Maclura pomifera extract, Male rat, Sperm, Reproductive system Erkek Ratlarda Maclura pomifera Ekstraktının Sisplatin ile Oluşturulmuş Üreme Sistemi Hasarı Üzerine Etkisi ÖzetBu çalışmanın amacı, maclura pomifera (MP) (sitotoksik, anti-tümöral, yangı önleyici, analjezik/ağrı giderici, ve antioksidan olarak bilinen) ekstraktının sisplatin (ROS (Reaktif oksijen türevleri) -oluşturucu yan etkili anti-tümöral ajan) uygulanan erkek ratların spermatolojik parametreleri üzerine etkisini incelemekti. Araştırmada 8 haftalık yaşta, 250-300 g canlı ağırlığa sahip 17 adet erkek Sprague Dawley ırkı rat kullanıldı. Üç deney grubu oluşturuldu; Grup 1 (n=5): kontrol grubu, hayvanlara intraperitonal (IP) serum fizyolojik enjeksiyonuyla birlikte, enjeksiyondan 5 gün öncesi ve sonrası boyunca oral gavaj yoluyla yine serum fizyolojik verildi. Grup 2 (n=6): Sisplatin (CP) grubu, hayvanlara bir kez IP 7 mg/kg CP enjeksiyonundan 5 gün öncesi ve sonrası boyunca oral yolla serum fizyolojik verildi. Grup 3 (n=6): MP + CP grubu, hayvanlara bir kez İP 7 mg/kg CP enjeksiyonuyla birlikte, enjeksiyondan 5 gün öncesi ve sonrası boyunca oral yolla günlük 500 mg/kg MP ekstraktı verildi. Deney sonunda ratlar dekapite edilerek testis ve kauda epididimis ağırlıkları ile epididimal sperm parametreleri incelendi. CP enjeksiyonu, sperm motilitesi ve yoğunluğunu önemli derecede (P<0.05) düşürdü ve ölü spermatozoa sayısını ar...

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Exposure to Bleomycin, Etoposide, and Cis-Platinum Alters Rat Sperm Chromatin Integrity and Sperm Head Protein Profile1

Cited by 38 publications

References 38 publications

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Epigenetic: a molecular link between testicular cancer and environmental exposures

Erkek Ratlarda Maclura pomifera Ekstraktının Sisplatin ile Oluşturulmuş Üreme Sistemi Hasarı Üzerine Etkisi

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