Genomic imprinting in disruptive spermatogenesis

Marques, C. Joana; Carvalho, Filipa; Sousa, Mário; Barros, Alberto

doi:10.1016/s0140-6736(04)16256-9

Cited by 325 publications

(246 citation statements)

References 5 publications

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“…[79][80][81][82][83][84][85][86] Abnormal methylation was observed in not only paternally methylated ICRs but also maternally methylated ICRs. At present, it is unclear how defects in methylation imprints are brought about in these patients, but one explanation could be aminoacid sequence variations in DNMT3L.…”

Section: Molar Pregnancy Infertility Assisted Reproductive Technolomentioning

confidence: 99%

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Tomizawa

Sasaki

2012

J Hum Genet

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Genomic imprinting is an epigenetic gene-marking phenomenon that occurs in the germline, whereby genes are expressed from only one of the two parental copies in embryos and adults. Imprinting is essential for normal mammalian development and its disruption can cause various developmental defects and diseases. The process of imprinting in the germline involves DNA methylation of the imprint control regions (ICRs), and resulting parental-specific methylation imprints are maintained in the zygote and act as the marks controlling imprinted gene expression. Recent studies in mice have revealed new factors involved in imprint establishment during gametogenesis and maintenance during early development. Clinical studies have identified cases of imprinting disorders where involvement of factors shared by multiple ICRs for establishment or maintenance is suspected. These include Beckwith-Wiedemann syndrome, transient neonatal diabetes, Silver-Russell syndrome and others. More severe disruptions can lead to recurrent molar pregnancy, miscarriage or infertility. Imprinting defects may also occur during assisted reproductive technology or cell reprogramming. In this review, we summarize our current knowledge on the mechanisms of imprint establishment and maintenance, and discuss the relationship with various human disorders.

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Section: Molar Pregnancy Infertility Assisted Reproductive Technolomentioning

confidence: 99%

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Tomizawa

Sasaki

2012

J Hum Genet

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“…Epigenetic abnormalities are associated with imprinting diseases (Gosden et al, 2003), molar pregnancies or certain childhood cancers. A paternal role in transmitting imprinting disorders is reported (Marques et al, 2004) and it is suggested that imprinting disorders are increased in babies from assisted reproduction. Genomic imprinting regulates whether the paternally or maternally inherited allele is expressed by silencing the reciprocal allele using methylation-induced blockage of target sequences or other mechanisms controlled by methylation (La Salle and Trasler, 2006).…”

Section: Structural Chromosomal Aberrationsmentioning

confidence: 99%

Paternal age and reproduction

Sartorius

Nieschlag

2009

Human Reproduction Update

291

212

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background: Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known.methods: We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal.results: This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. conclusion: Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedures.

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“…This locus is paternally imprinted and hypermethylated in normospermic men. Changes in DNA methylation profiles in spermatozoa is found in association with oligozoospermia, with some studies indicating up to 46 % of men with reduced sperm counts have altered DNA methylation profiles in their sperm [14][15][16][17]. Hypomethylation of normally hypermethylated paternally imprinted loci is associated with various cancers, disorders of growth and metabolism such as BeckwithWiedemann and disorders in neurodevelopment, cognition, and behaviour [18,19].…”

Section: Discussionmentioning

confidence: 99%

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

Berthaut

Montjean

Dessolle

et al. 2013

J Assist Reprod Genet

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Introduction Temozolomide is an oral alkylating agent with proven efficacy in recurrent high-grade glioma. The antitumour activity of this molecule is attributed to the inhibition of replication through DNA methylation. However, this methylation may also perturb other DNA-dependent processes, such as spermatogenesis. The ability to father a child may be affected by having this treatment. Here we report a pregnancy and a baby born after 6 cures of temozolomide. Methods The quality of gametes of the father has been studied through these cures and after the cessation of treatment. Sperm parameters, chromosomal content and epigenetic profiles of H19, MEST and MGMT have been analysed.Results Sperm counts decrease significantly and hypomethylation of the H19 locus increase with time even staying in the normal range. Conclusion This is the first report of an epigenetic modification in sperm after temozolomide treatment suggesting a potential risk for the offspring. A sperm cryopreservation before the initiation of temozolomide treatment should be recommended.

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Genomic imprinting in disruptive spermatogenesis

Cited by 325 publications

References 5 publications

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Paternal age and reproduction

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

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