IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch

Li, Tao; Vu, Thanh H.; Ulaner, Gary A.; Littman, E.; Ling, Jianqun; Chen, Huiling; Hu, Ji-Fan; Behr, Barry; Giudice, Linda C.; Hoffman, Andrew R.

doi:10.1093/molehr/gah230

Cited by 166 publications

(101 citation statements)

References 49 publications

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“…Several recent papers indicate that the DNA methylation profile is dramatically altered in the spermatozoa of infertile men [35][36][37]. Moreover, we already know that the incidence of imprinting defects such as Angelman syndrome (AS) and Beckwith-Weidemann syndrome (BWS) is elevated in children born as a result of assisted conception [38]. Assessment of such factors is likely to be a key issue for the 6th edition of the WHO manual as we move the consideration of normal sperm function beyond the traditional realms of 'fertilizing potential' and into the factors responsible for the initiation of normal embryonic development.…”

Section: The Futurementioning

confidence: 99%

Whither must spermatozoa wander? The future of laboratory seminology

Aitken

2010

Asian J Androl

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This commentary celebrates the publication of the 5th edition of the World Health Organization Laboratory Manual for the Examination and Processing of Human Semen. This is the most complete text to date on the creation of a conventional semen profile and includes invaluable reference limits for specific aspects of semen quality based on the analysis of over 1 900 recent fathers. The new edition of the manual also includes detailed protocols for monitoring different aspects of sperm function and new chapters on the preparation of spermatozoa for assisted conception and cryopreservation. Given that this publication is the definitive statement on how to perform a descriptive semen analysis, we might speculate on the future of this field and the sorts of tests that might feature in future editions of the manual. Cell biologists are currently being empowered by the 'omics revolution, which is placing at their disposal technologies of unprecedented power to examine the biochemical composition of cells such as spermatozoa. Indeed, spermatozoa are perfect vehicles for this kind of analysis because they can be obtained as extremely pure suspensions, exist naturally in isolation and can be induced to express their capacity for fertilization and the initiation of embryonic development in vitro. The application of 'omics technologies to these cells, in concert with detailed assessments of their functional competence, should provide insights into the biochemical basis of defective semen quality. This information will then help us understand the causes of male infertility and to develop rational methods for its treatment and possible prevention. Keywords: assisted conception, DNA damage, male infertility, miscarriage, semen, seminology, spermatozoa 1 In the beginning A long long time ago, when in vitro fertilization (IVF) was in its first flush of youth and Intracytoplasmic sperm injection (ICSI) had not driven seminology into the reproductive wilderness, the development of robust methods for the diagnosis and treatment of male infertility was regarded as a noble cause worthy of engagement.In those far-off days, the descriptive semen profile was the only means we had of determining the fertility of men attending infertility clinics. This profile focused on an analysis of sperm number, motility and morphology underpinned by the fundamental belief that fertility is essentially a war of attrition. According to this model, the ejaculate must contain more than a certain critical number of motile, morphologically normal spermatozoa in order to withstand the cellular carnage that inevitably accompanies the perilous transition from the point of insemination to the site of fertilization. In diagnostic terms, the concept that male fertility is essentially 'a numbers game' resulted in a preoccupation with threshold counts for sperm number, motility and morphology that define the conventional semen profile, even to this day. The belief that fertility is entirely dependent on sperm number was, ironically,

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Section: The Futurementioning

confidence: 99%

Whither must spermatozoa wander? The future of laboratory seminology

Aitken

2010

Asian J Androl

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“…There is some commonality in imprinted genes among mice, cattle, and humans, and mice have been used as a model to study aberrant imprinting [31]. Li et al 2005 [32] used inbred mice to create a model in which allele specific changes in DNA and histone methylation could be followed. Crossing two species of inbred mice to create an F1 hybrid with polymorphisms in imprinted alleles allowed parental alleles to be distinguished, making it possible to observe allele specific changes in DNA and histone methylation, and for examining the mechanisms by which ART may affect phenotype.…”

Section: Use Of the Mouse To Understand Gene Function And Regulation mentioning

confidence: 99%

Virtues and limitations of the preimplantation mouse embryo as a model system

Taft

2008

Theriogenology

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The mouse is the most widely used model of preimplantation embryo development, but is it a good model? Its small size, prolificacy and ease of handling make the mouse a relatively low cost, readily available and attractive alternative when embryos from other species are difficult or expensive to obtain. However, the real power of the mouse as a model lies in mouse genetics. The development of inbred mouse strains facilitated gene discovery as well as our understanding of gene function and regulation while the development of tools to introduce precise genetic modifications uniquely positioned the mouse as a powerful model system for uncovering gene function. However, all models have limitations; the small size of the mouse limits tissue availability and manipulations that can be performed and differences in physiology among species may make it inappropriate to extrapolate from the mouse to other species. Thus, rather than extrapolating directly from the mouse to other species, it may be more useful to use the mouse as a model system for developing and refining hypotheses to be tested directly in species of interest. In this brief review, the value of the preimplantation mouse embryo as a model is considered, both as a model for other species and as a model for the mouse, as understanding the virtues and limitations of the mouse as a model system is essential to its appropriate use.

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“…The effect of in vitro fertilization (IVF) on DNA methylation in mouse embryos has been demonstrated in many studies (5,(7)(8)(9). Small epidemiology studies in humans have suggested a 4-to 9-fold increased incidence of BeckwithWiedemann syndrome (BWS) among children conceived by IVF or intracytoplasmic sperm injection (ICSI) (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Zheng

Shi

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Assisted reproductive technology (ART) includingin vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been shown to be associated with abnormal genomic imprinting, thus increasing the incidence of imprinting disorders such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) in ART-conceived children. Furthermore, a recent study described abnormal DNA methylation in clinically normal children conceived by ART. However, data from different studies are conflicting or inconclusive. This study examined DNA methylation patterns of multiple imprinted genes in children born after ART to primarily evaluate the impact of ART on genomic imprinting. A total of 101 newborns conceived by ART (40 ICSI and 61 IVF) and 60 naturally conceived newborns were involved in our study. After obtaining the approval of the Institutional Ethics Committee, umbilical cord blood was collected from each infant. Genomic DNA was isolated from each blood sample and treated using sodium bisulfite. Subsequently, using methylation-specific PCR (MS-PCR), we analyzed six differentially methylated regions (DMRs) including KvDMR1, SNRPN, MEST, MEG3, TNDM and XIST. Meanwhile, information regarding twin pregnancies, gestational age, and birth weight of the neonates was documented. None of the cases presented with phenotypic abnormalities. Children conceived by ART were more likely to have low birth weight and to be born before term, compared with children conceived spontaneously. However, 7 months to 3 years of clinical follow-up showed that none of the children had clinical symptoms of any imprinting diseases. Furthermore, the MS-PCR results showed that all 161 children had normal DNA methylation patterns at six DMRs despite the different mode of conception. Our data did not indicate a higher risk of DNA-methylation defects in children born after ART. However, further studies using quantitative methods are needed to confirm these results.

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IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch

Cited by 166 publications

References 49 publications

Whither must spermatozoa wander? The future of laboratory seminology

Whither must spermatozoa wander? The future of laboratory seminology

Virtues and limitations of the preimplantation mouse embryo as a model system

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

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