Testicular and sperm DNA damage after treatment with fludarabine for chronic lymphocytic leukaemia
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It is found that testicular damage occurred within a month, as indicated by reduced testicular volume, oligozoospermia, elevated FSH and LH, and lower testosterone concentrations, and DNA damage in the spermatozoa was marked by 7 months of FLU treatment.Abstract:
This study investigated whether chemotherapy using fludarabine (FLU) caused testicular damage and if cytotoxicity could be detected as sperm DNA damage in the single cell Comet assay. A patient with chronic lymphocytic leukaemia requesting preservation of fertility was treated with seven monthly cycles of fludarabine (45.8 mg total dose per cycle). Testicular assessments, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone measurements, semen analysis and sperm Comet assays were carried out at presentation (pre-FLU therapy), after 1 and 7 months of FLU treatment, and finally at 11 months after completion of chemotherapy. We found that testicular damage occurred within a month, as indicated by reduced testicular volume, oligozoospermia, elevated FSH and LH, and lower testosterone concentrations. Spermatozoa with a large range of DNA damage were detected in the samples from both the control and treated men. DNA damage in the spermatozoa was marked by 7 months of FLU treatment. The high levels of sperm DNA damage seen during and possibly persisting after treatment suggests that caution should be exercised if the ejaculates from these men are used for in-vitro fertility treatment. Further experiments are needed to assess the biological significance of these DNA changes; it may, however, be prudent at present to be cautious when counselling these patients.read more
Citations
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Role of sperm chromatin abnormalities and DNA damage in male infertility
Ashok Agarwal,Tamer M. Said +1 more
TL;DR: Screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction, and treatment should include methods for prevention of spermDNA damage.
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The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development.
TL;DR: High loads of DNA damage measured by the Comet assay were predictive of failure of embryo development after ICSI, and it is likely that sperm with DNA damage contributed to successful fertilization and in-vitro development.
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Sperm DNA damage in male infertility: Etiologies, assays, and outcomes
TL;DR: The structure of human sperm chromatin, the etiology and mechanisms of sperm DNA damage, current tests available to assess sperm DNA integrity, and effect of spermDNA integrity on reproductive outcomes are reviewed.
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Genetic and teratogenic effects of cancer treatments on gametes and embryos
TL;DR: No increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy, and the use of assisted reproductive technologies and micromanipulation techniques might increase this risk.
References
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World Health Organization Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 4th ed.
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Relative Impact of Oxidative Stress on the Functional Competence and Genomic Integrity of Human Spermatozoa
TL;DR: Human spermatozoa exposed to increasing levels of oxidative stress achieved through the stimulation of endogenous oxidant generation with NADPH or direct exposure to hydrogen peroxide exhibited significantly elevated levels of DNA damage and yet continued to express an enhanced capacity for sperm-oocyte fusion.
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Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro.
TL;DR: Since extremely poor semen samples are the indication for intracytoplasmic sperm injection, there is a high likelihood that sperm with fragmented DNA may be selected by chance and used for oocyte injection, resulting in poor fertilization and/or cleavage rates.
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Origin of dna damage in ejaculated human spermatozoa
TL;DR: The possible origins of DNA damage in ejaculated human spermatozoa are discussed, how these spermutozoa arrive in the ejaculate of some men, and what consequences they may have if they succeed in their genetic project are discussed.
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The Amoroso Lecture. The human spermatozoon--a cell in crisis?
TL;DR: Establishing the mechanisms for free radical generation by the male germ line and determining the factors that influence this activity are important objectives for future research in this area.