Gonadal Function in Patients with Testicular Germ Cell Tumors

Tomomasa, Hiroshi; Oshio, Shigeru; Ashizawa, Yoshio; Kamiyama, Yutaka; Okano, Yoshinori; Iiyama, Tetsuro; Sato, Shigeo; Shimizu, Hiroshi; Umeda, Takashi

doi:10.1080/01485010290099318

Cited by 9 publications

(4 citation statements)

References 26 publications

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“…Relatively few studies have examined the impact of BEP treatment on the number of spermatozoa in men immediately after the completion of chemotherapy. The spermatozoal concentration in men who have undergone BEP gradually improves after completion of treatment (Tomomasa et al, 2002), and thus it is difficult to compare the response in humans with the results of the current study.…”

Section: Discussionmentioning

confidence: 92%

Effects of Chemotherapeutic Agents for Testicular Cancer on the Male Rat Reproductive System, Spermatozoa, and Fertility

Bieber

Marcon

Hales

et al. 2006

Journal of Andrology

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Testicular cancer is the most common cancer affecting men of reproductive age. Advances in treatment of the disease, which include the coadministration of bleomycin, etoposide, and cisplatinum (BEP), have brought the cure rate to over 90%. This high cure rate, coupled with the young age of patients, makes elucidation of the impact of the treatment on reproductive function, fertility, and progeny outcome increasingly important. The goal of this study was to determine the effects of BEP, in doses analogous to those given to humans, on the male reproductive system, spermatozoa, fertility, and progeny outcome in an animal model. Male Sprague-Dawley rats were treated daily with BEP for 3 cycles of 3 weeks each, for a total of 9 weeks. After 6 and 9 weeks, males were mated to 2 groups of untreated females. BEP treatment resulted in decreases in testicular and epididymal weights of 52% and 28%, respectively, when compared to control. Decreased testis and epididymis weights were accompanied by impairment of spermatogenesis and by a decrease in spermatozoal count of nearly 90% (11.9 ϫ 10 7 spermatozoa per caput epididymidis in control vs 1.65 ϫ 10 7 in BEP-treated rats). The percent of motile spermatozoa in the treated rats was more than 30% lower than in controls. Defects in the flagella of spermatozoa increased by more than twofold in the midpiece, and by more than sixfold in the principal piece. Paternal BEP treatment, for either 6 or 9 weeks, did not affect fertility, pre-or postimplantation loss, litter size, or sex ratio among progeny on gestation day 21. In contrast, among the pregnancies allowed to proceed to delivery, a significant number of pups sired by males treated with BEP for 9 weeks died between birth and postnatal day 2; this was not observed in pups sired by males treated for 6 weeks. Markers of postnatal development were not affected in the surviving offspring from either group. Thus, despite the dramatic effects of the testicular cancer drug regimen on spermatogenesis, the numbers of spermatozoa, and their motility and morphology, male rats were fertile. While fetal development was apparently normal, early postnatal mortality, which may be associated with a delay in parturition, was elevated among the progeny sired by males exposed to BEP for 9 weeks.

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Section: Discussionmentioning

confidence: 92%

Effects of Chemotherapeutic Agents for Testicular Cancer on the Male Rat Reproductive System, Spermatozoa, and Fertility

Bieber

Marcon

Hales

et al. 2006

Journal of Andrology

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“…Additionally, rodents exposed to cisplatin showed a decrease in the weight of both the testes and epididymides, as well as a reduction in testis size [ 41 , 42 ]. In some chronic cisplatin chemotherapy models, damage to the germ and spermatogenesis led to a lower number of spermatozoa, which was decreased by more than 90% compared to that in the untreated groups [ 43 ]. Furthermore, in vitro studies have also shown that C18-4 spermatogonia cells are sensitive to cisplatin, and cisplatin significantly increases DNA damage and telomere dysfunction in spermatogonia [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture

Park

Kim

Lee

et al. 2022

IJMS

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Chemotherapy is used for childhood cancer but may lead to infertility in patients. Spermatogonia stem cells are present in the testes of prepubertal boys, although they do not produce sperm at this age. Herein, we evaluated the toxicity of cisplatin, a known medicine for cancer treatment, in neonatal mouse testes using in vitro organ culture. Mouse testicular fragments (MTFs) derived from 5.5-d postpartum mouse testes were exposed to 1–10 μg/mL cisplatin. The results showed that cisplatin significantly downregulated the expression of germ cell marker genes, including differentiated and undifferentiated, in a dose-dependent manner. In particular, a high dose of cisplatin (10 μg/mL) led to germ cell depletion. In addition, the expression levels of the Sertoli cell marker gene, the number of SOX9+ Sertoli cells, and the levels of SOX9 protein were markedly decreased in cisplatin-treated MTFs compared to controls. The mRNA expression of steroidogenic enzyme-related genes significantly increased in cisplatin-treated MTFs, except for estrogen receptor 1 (Esr1). Consistently, 3β-hydroxysteroid dehydrogenase protein was also observed in the interstitial regions of cisplatin-treated MTFs. Altogether, our findings showed a significant impairment in germ cell development, Sertoli cell survival, and steroidogenesis in the MTFs of cisplatin-treated mice.

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“…Використання сучасних методик опромінення і засобів захисту ста вить за мету відновлення сперматогенезу незалежно від застосованої променевої терапевтичної дози, що відбувається не раніше, ніж через 6 міс. Надійне екра нування яєчок значно послаблює їх ураження при оп роміненні таза, але розсіяна доза (зазвичай близько 2% від загальної) часто перевищує поріг пригнічення сперматогенезу (0,5% від загальної дози) [22,34,35].…”

Section: променева терапія і сперматогенезunclassified

“…Using modern tech niques of exposure and protection aims to restore spermatogenesis regardless of the applied radiation therapeutic dose, which is not earlier than 6 months. Reliable screening testicular lesions sig nificantly reduces their pelvic irradiation, but scat tered dose (usually about 2 % of the total) often exceeds threshold inhibition of spermatogenesis (0.5 % of dose) [22,34,35].…”

Section: променева терапія і сперматогенезmentioning

confidence: 99%

Influence radio and chemotherapy cancer patients to development of male infertility (literature review)

Gavrysh

2016

Probl Radiac Med Radiobiol

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Обсяг еякуляту, мл / the volume of ejaculate, ml 1,5 мл і більше / 1.5 ml and more Загальна кількість сперматозоїдів, млн / the total number of spermatozoa, million 39 і більше / 39 and over Концентрація сперматозоїдів, млн в 1 мл / the concentration of spermatozoa, million in 1 ml 15 і більше / 15 or more Загальна рухливість сперматозоїдів,% / total spermatozoa motility, % 40 і більше / 40 and more Сперматозоїдів з прогресивним рухом,% / spermatozoa with progressive movement, % 32 і більше / 32 and more Життєздатність,% / viability, % 58 і більше / 58 and more Морфологія: нормальних форм,% / morphology: normal forms, % 4 і більше / 4 and more

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Gonadal Function in Patients with Testicular Germ Cell Tumors

Cited by 9 publications

References 26 publications

Effects of Chemotherapeutic Agents for Testicular Cancer on the Male Rat Reproductive System, Spermatozoa, and Fertility

Effects of Chemotherapeutic Agents for Testicular Cancer on the Male Rat Reproductive System, Spermatozoa, and Fertility

Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture

Influence radio and chemotherapy cancer patients to development of male infertility (literature review)

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