Dataset Information

Assisted reproduction treatment and epigenetic inheritance.

ABSTRACT:

Background

The subject of epigenetic risk of assisted reproduction treatment (ART), initiated by reports on an increase of children with the Beckwith-Wiedemann imprinting disorder, is very topical. Hence, there is a growing literature, including mouse studies.

Methods

In order to gain information on transgenerational epigenetic inheritance and epigenetic effects induced by ART, literature databases were searched for papers on this topic using relevant keywords.

Results

At the level of genomic imprinting involving CpG methylation, ART-induced epigenetic defects are convincingly observed in mice, especially for placenta, and seem more frequent than in humans. Data generally provide a warning as to the use of ovulation induction and in vitro culture. In human sperm from compromised spermatogenesis, sequence-specific DNA hypomethylation is observed repeatedly. Transmittance of sperm and oocyte DNA methylation defects is possible but, as deduced from the limited data available, largely prevented by selection of gametes for ART and/or non-viability of the resulting embryos. Some evidence indicates that subfertility itself is a risk factor for imprinting diseases. As in mouse, physiological effects from ART are observed in humans. In the human, indications for a broader target for changes in CpG methylation than imprinted DNA sequences alone have been found. In the mouse, a broader range of CpG sequences has not yet been studied. Also, a multigeneration study of systematic ART on epigenetic parameters is lacking.

Conclusions

The field of epigenetic inheritance within the lifespan of an individual and between generations (via mitosis and meiosis, respectively) is growing, driven by the expansion of chromatin research. ART can induce epigenetic variation that might be transmitted to the next generation.

SUBMITTER: van Montfoort AP

PROVIDER: S-EPMC3282574 | biostudies-literature | 2012 Mar-Apr

REPOSITORIES: biostudies-literature

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Publications

Assisted reproduction treatment and epigenetic inheritance.

van Montfoort A P A AP Hanssen L L P LL Hanssen L L P LL de Sutter P P Viville S S Geraedts J P M JP de Boer P P

Human reproduction update 20120119 2

<h4>Background</h4>The subject of epigenetic risk of assisted reproduction treatment (ART), initiated by reports on an increase of children with the Beckwith-Wiedemann imprinting disorder, is very topical. Hence, there is a growing literature, including mouse studies.<h4>Methods</h4>In order to gain information on transgenerational epigenetic inheritance and epigenetic effects induced by ART, literature databases were searched for papers on this topic using relevant keywords.<h4>Results</h4>At t ...[more]

PMID: 22267841

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Project description:BACKGROUND AND AIMS: Epigenetics is defined as mechanisms that regulate gene expression without base sequence alteration. One molecular basis is considered to be DNA cytosine methylation, which reversibly modifies DNA or chromatin structures. Although its correlation with epigenetic inheritance over generations has been circumstantially shown, evidence at the gene level has been limited. The present study aims to find genes whose methylation status directly correlates with inheritance of phenotypic changes. METHODS: DNA methylation in vivo was artificially reduced by treating rice (Oryza sativa ssp. japonica) seeds with 5-azadeoxycytidine, and the progeny were cultivated in the field for > 10 years. Genomic regions with changed methylation status were screened by the methylation-sensitive amplified polymorphysm (MSAP) method, and cytosine methylation was directly scanned by the bisulfite mapping method. Pathogen infection with Xanthomonas oryzae pv. oryzae, race PR2 was performed by the scissors-dip method on mature leaf blades. KEY RESULTS: The majority of seedlings were lethal, but some survived to maturity. One line designated as Line-2 showed a clear marker phenotype of dwarfism, which was stably inherited by the progeny over nine generations. MSAP screening identified six fragments, among which two were further characterized by DNA blot hybridization and direct methylation mapping. One clone encoding a retrotransposon gag-pol polyprotein showed a complete erasure of 5-methylcytosines in Line-2, but neither translocation nor expression of this region was detectable. The other clone encoded an Xa21-like protein, Xa21G. In wild-type plants, all cytosines were methylated within the promoter region, whereas in Line-2, corresponding methylation was completely erased throughout generations. Expression of Xa21G was not detectable in wild type but was constitutive in Line-2. When infected with X. oryzae pv. oryzae, against which Xa21 confers resistance in a gene-for-gene manner, the progeny of Line-2 were apparently resistant while the wild type was highly susceptible without Xa21G expression. CONCLUSIONS: These results indicated that demethylation was selective in Line-2, and that promoter demethylation abolished the constitutive silencing of Xa21G due to hypermethylation, resulting in acquisition of disease resistance. Both hypomethylation and resistant trait were stably inherited. This is a clear example of epigenetic inheritance, and supports the idea of Lamarckian inheritance which suggested acquired traits to be heritable.

Project description:BACKGROUND: One of the major factors impacting on a couple's relationship is the desire to have children. To many couples having a child is a confirmation of their love and relationship and a means to deepen and develop their intimate relationship. At the same time parental stress can impact on relationship quality. Relationship quality in lesbian couples is, currently, sparsely studied. The aim of the present study was to compare lesbian and heterosexual couples' perceptions of their relationship quality at the commencement of assisted reproduction, and to relate this to background data such as educational level, having previous children and, for lesbian couples, the use of a known versus anonymous donor. METHODS: The present study is part of the prospective longitudinal 'Swedish study on gamete donation', including all fertility clinics performing donation treatment in Sweden. Of a consecutive cohort of 214 lesbian couples about to receive donor insemination and 212 heterosexual couples starting regular IVF treatment, 166 lesbian couples (78% response) and 151 heterosexual couples (71% response) accepted participation in the study. At commencement of assisted reproduction participants individually completed questionnaires including the instrument 'ENRICH', which is a standardized measure concerning relationship quality. RESULTS: In general, the couples rated their relationship quality as good, the lesbian couple better than the heterosexuals. In addition, the lesbian women with previous children assessed their relationship quality lower than did the lesbian woman without previous children. For heterosexual couples previous children did not influence their relationship quality. Higher educational levels reduced the satisfaction with the sexual relationship (P = 0.04) for treated lesbian women, and enhanced the rating of conflict resolution for treated lesbian women (P = 0.03) and their partners (P = 0.02). Heterosexual women with high levels of education expressed more satisfaction with communication in their relationship (P = 0.02) than did heterosexual women with lower educational levels. CONCLUSIONS: In this Swedish study sample of lesbian and heterosexual couples' relationships, we found that they were generally well adjusted and stable in their relationships when starting treatment with donated sperm or IVF, respectively. However, where lesbian women had children from a previous relationship, it decreased relationship quality. For the heterosexual couples previous children did not affect relationship quality.

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Dataset Information

Assisted reproduction treatment and epigenetic inheritance.

Background

Methods

Results

Conclusions

Publications

Assisted reproduction treatment and epigenetic inheritance.

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