Effect of temozolomide on male gametes: an epigenetic risk to the offspring?

Berthaut, Isabelle; Montjean, Debbie; Dessolle, Lionel; Morcel, Karine; Deluen, F.; Poirot, Catherine; Bashamboo, Anu; McElreavey, Ken; Ravel, Célia

doi:10.1007/s10815-013-9999-8

Cited by 18 publications

(12 citation statements)

References 18 publications

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“…In men with oligoasthenoteratozoospermia, methylation was markedly reduced at all CpGs, reaching statistical significance in subgroups with a sperm concentration of <10x10 6 /ml. These findings suggest that abnormal DNA methylation-mediated genomic imprinting is associated with oligoasthenoteratozoospermia and oligozoospermia (100)(101)(102)(103)(104)(105)(106)(107).…”

Section: Dna Methylation and Male Infertilitymentioning

confidence: 82%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

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Section: Dna Methylation and Male Infertilitymentioning

confidence: 82%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Methylation was obviously reduced in men diagnosed with oligoasthenoteratozoospermia at all CpGs, achieving statistical importance especially in patients with count < 10 × 106/ ml. Therefore, these discoveries recommend that atypical DNA methylation intervened genomic imprinting is connected with oligozoospermia and oligoasthenoteratozoospermia [125][126][127][128].…”

Section: Impact Of Epigenetic Regulation In Spermatogenesis and Male mentioning

confidence: 99%

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

Laleethambika

Venugopal

Chandran

et al. 2018

SN Compr. Clin. Med.

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Diabetes mellitus (DM) represents one of the major threats to human health all over the world, affecting almost every system of the body. Its prevalence is escalating globally and is associated with reproductive impairment in both males and females. Reports on male infertility due to DM is lacking since most affected individuals are unaware of their infertility condition due to the late onset of DM. Glucose metabolism is an imperative occasion in spermatogenesis, causing adverse effects on male fertility, principally on sperm DNA quality, motility, and ingredients of seminal plasma. DM is coupled with an increased oxidative stress (OS), causing sperm nuclear and mitochondrial DNA damage. Reactive oxygen species (ROS) hassles the fluidity of sperm plasma membrane, decreases sperm motility and ability to fuse with oocyte as well as altering the sperm DNA integrity. Lamentably, spermatozoa cannot repair the damage initiated by excessive ROS as they do not have the cytoplasmic enzymes required to achieve the repair. Diabetes may impact the epigenetic change during spermatogenesis which may be inherited through male gamete to more than one generation increasing the risk of diabetes in offspring. Administration of antioxidants in male infertility has started to pull in significant intrigue. Many studies have shown that antioxidants amazingly reduce the oxidative stress markers and boost the antioxidant enzymes. Currently treatment strategies are aimed at lowering ROS levels to maintain normal cell function. This review highlights the potential impact of DM on sperm DNA integrity, epigenetic dysregulation and efficacy of antioxidant therapy.

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“…FSH: follicle stimulating hormone, LH: luteinizing hormone, SSC: spermatogonial stem cell. [24][25][26][27][28][29][30]77,81,83], spermatogonia and spermatocytes [24,43,[46][47][48]52,53,55,89,[96][97][98], spermatozoa [56,62,98,[108][109][110][111]125,126,[129][130][131]135,136] and progeny [55,[109][110][111][143][144][145][146][147][148][149]151] following chemotherapy administration during childhood and adulthood. Animal species and the age at which the chemotherapy treatments achieved are specified in parentheses.…”

Section: Discussionmentioning

confidence: 99%

“…DNA methylation profiles has been impaired in 46% of oligozoospermic patients [134]. Hypomethylation of H19, a paternally imprinted gene, has been observed almost a year after the first day of initial treatment in one patient diagnosed for anaplastic oligodendroglioma [135]. Following the administration of cancer drugs, a reduced expression of DNA methyltransferases and disrupted DNA methylation patterns has been reported in rodent spermatozoa [136,137].…”

Section: Sperm Nuclear Abnormalitiesmentioning

confidence: 99%

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

Delessard

Saulnier

Rives

et al. 2020

IJMS

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Over the last decade, the number of cancer survivors has increased thanks to progress in diagnosis and treatment. Cancer treatments are often accompanied by adverse side effects depending on the age of the patient, the type of cancer, the treatment regimen, and the doses. The testicular tissue is very sensitive to chemotherapy and radiotherapy. This review will summarize the epidemiological and experimental data concerning the consequences of exposure to chemotherapy during the prepubertal period or adulthood on spermatogenic progression, sperm production, sperm nuclear quality, and the health of the offspring. Studies concerning the gonadotoxicity of anticancer drugs in adult survivors of childhood cancer are still limited compared with those concerning the effects of chemotherapy exposure during adulthood. In humans, it is difficult to evaluate exactly the toxicity of chemotherapeutic agents because cancer treatments often combine chemotherapy and radiotherapy. Thus, it is important to undertake experimental studies in animal models in order to define the mechanism involved in the drug gonadotoxicity and to assess the effects of their administration alone or in combination on immature and mature testis. These data will help to better inform cancer patients after recovery about the risks of chemotherapy for their future fertility and to propose fertility preservation options.

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Effect of temozolomide on male gametes: an epigenetic risk to the offspring?

Cited by 18 publications

References 18 publications

DNA methylation in spermatogenesis and male infertility

DNA methylation in spermatogenesis and male infertility

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

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