DNA damaging effect of paclitaxel in the epididymal sperms as a chemotherapeutic agent and possible remedies to prevent this effect: A study on reproductive potential of male cancer patients of reproductive age

İli, Pınar; Sari, Fikret; Bucak, Mustafa Numan; Öztürk, Caner; Güngör, Salim; Ataman, Mehmet Bozkurt

doi:10.1016/j.theriogenology.2019.04.015

Cited by 10 publications

(6 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All observations above allow us to assume that TBBPA-BDBPE may have the potential to bind to tubulin and thereby interfere with tubulin dynamics, which may be the mechanism for testicular damage caused by TBBPA-BDBPE. In fact, some natural compounds and their synthetic analogues capable of targeting tubulin, such as vinblastine and paclitaxel, have been demonstrated to have side effects on male fertility. − Moreover, several rodent studies reported that tubulin-targeting fungicides, such as carbendazim, caused severe testicular damage, along with microtubule damage . To the best of our knowledge, this is the first study reporting that an environmental chemical may interfere with tubulin dynamics and possibly contribute to testicular damage in mammals.…”

Section: Resultsmentioning

confidence: 84%

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) impairs Postnatal Testis Development in Mice: The Microtubule Cytoskeleton as a Sensitive Target

Xiong

Zhang

et al. 2023

Environ. Health

View full text Add to dashboard Cite

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a widely used flame retardant, has been frequently detected in various environmental compartments, but its health hazard remains largely unknown. Here, we investigated the adverse effects of TBBPA-BDBPE (50 and 1000 μg/kg/day) on postnatal testis development in CD-1 mice and the underlying mechanism. Following the first week of maternal exposure, neonatal mice in the high-dose group exhibited reduced seminiferous tubule area, fewer Sertoli cells and germ cells, and damaged microtubules in Sertoli cells; even microtubule damage was also observed in the low-dose group. When exposure extended to adulthood, male offspring in the high-dose group presented more remarkable alterations in reproductive parameters, including reduced sperm count; in the low-dose group, microtubule damage was also observable, along with blood−testis barrier impairment. Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization. Moreover, we observed attenuated microtubules in mouse Sertoli cells in vitro (TM4) following TBBPA-BDBPE treatment, suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics. This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.

show abstract

Section: Resultsmentioning

confidence: 84%

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) impairs Postnatal Testis Development in Mice: The Microtubule Cytoskeleton as a Sensitive Target

Xiong

Zhang

et al. 2023

Environ. Health

View full text Add to dashboard Cite

show abstract

“…To explore the relations between the mtDNA G4s and spermatozoa, sperm were treated with chemicals that have been reported to cause negative effects and lead to pathological damage (e.g., DNA damage, respiratory depression, oxidative stress injury). Paclitaxel induces DNA damage in sperm . Amitriptyline and mirtazapine act generally as inhibitors of complex I and complex IV of the electron transport chain .…”

Section: Resultsmentioning

confidence: 99%

“…Paclitaxel induces DNA damage in sperm. 25 Amitriptyline and mirtazapine act generally as inhibitors of complex I and complex IV of the electron transport chain. 26 H 2 O 2 is the most commonly used inducer of oxidative stress injury in vitro.…”

Section: Resultsmentioning

confidence: 99%

Dissecting Sperm Mitochondrial G-Quadruplex Structures Using a Fluorescent Probe Biomarker to Monitor and Regulate Fertilization Capability

Huang

et al. 2023

ACS Sens.

View full text Add to dashboard Cite

To monitor the levels of mitochondrial DNA Gquadruplexes (mtDNA G4s) in spermatozoa and to explore the possibility using mtDNA G4s as a reliable marker in patients with multiple clinical insemination failures, a novel chemical TPE-mTO probe engineered in our previous work was used on both samples from the mice sperm and from patients with fertilization failure. Expression of valosin-containing protein and the zona-free hamster egg assay were used to evaluate mitophagy and human sperm penetration. RNA-sequencing was used to explore expression changes of key genes affected by mtDNA G4s. Results showed that the probe can track mtDNA G4s in spermatozoa easily and quickly with fewer backgrounds. Significantly increased mtDNA G4s were also found in patients with fertilization failure, using the flow-cytometry-based TPE-mTO probe detection method. A sperm−hamster egg penetration experiment showed that abnormal fertilization caused by increased mtDNA G4s can be effectively restored by a mitophagy inducer. This study provides a novel method for monitoring etiological biomarkers in patients with clinical infertility and treatment for patients with abnormal fertilization caused by mtDNA G4 dysfunction.

show abstract

“…In this scenario, resveratrol administration preserved the metabolic pathways involved in erectile function and provided functional protection of prostatic cancer patients undergoing radiotherapy [ 85 ]. Another recent study on the use of resveratrol during cancer therapy determined that the administration of resveratrol during treatment with paclitaxel, diminished DNA fragmentation of rabbit epididymal spermatozoa after cryopreservation [ 86 ]. All these results show that resveratrol not only modulates the male reproductive function, but is capable of exerting a direct and protective effect on spermatogenesis.…”

Section: Resveratrol Effects On Malesmentioning

confidence: 99%

“…In this scenario, resveratrol has been extensively used as a suitable antioxidant supplement to semen extenders in human, mouse, ram, bull, buffalo, and boar semen [ 75 , 86 , 112 , 113 , 114 , 115 , 116 ]. In particular, in vivo and in vitro studies indicated that resveratrol improves sperm quality during the cryopreservation process [ 74 , 87 ], thanks to its protective function against lipid peroxidation (LPO) and DNA damage caused by ROS [ 75 , 117 ].…”

Section: Resveratrol Effects On Malesmentioning

confidence: 99%

The Role of Resveratrol in Mammalian Reproduction

et al. 2020

View full text Add to dashboard Cite

Resveratrol is one of the most investigated natural polyphenolic compounds and is contained in more than 70 types of plants and in red wine. The widespread interest in this polyphenol derives from its antioxidant, anti-inflammatory and anti-aging properties. Several studies have established that resveratrol regulates animal reproduction. However, the mechanisms of action and the potential therapeutic effects are still unclear. This review aims to clarify the role of resveratrol in male and female reproductive functions, with a focus on animals of veterinary interest. In females, resveratrol has been considered as a phytoestrogen due to its capacity to modulate ovarian function and steroidogenesis via sirtuins, SIRT1 in particular. Resveratrol has also been used to enhance aged oocyte quality and as a gametes cryo-protectant with mainly antioxidant and anti-apoptotic effects. In males, resveratrol enhances testes function and spermatogenesis through activation of the AMPK pathway. Furthermore, resveratrol has been supplemented to semen extenders, improving the preservation of sperm quality. In conclusion, resveratrol has potentially beneficial effects for ameliorating ovarian and testes function.

show abstract

DNA damaging effect of paclitaxel in the epididymal sperms as a chemotherapeutic agent and possible remedies to prevent this effect: A study on reproductive potential of male cancer patients of reproductive age

Cited by 10 publications

References 67 publications

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) impairs Postnatal Testis Development in Mice: The Microtubule Cytoskeleton as a Sensitive Target

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) impairs Postnatal Testis Development in Mice: The Microtubule Cytoskeleton as a Sensitive Target

Dissecting Sperm Mitochondrial G-Quadruplex Structures Using a Fluorescent Probe Biomarker to Monitor and Regulate Fertilization Capability

The Role of Resveratrol in Mammalian Reproduction

Contact Info

Product

Resources

About