Dataset Information

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.

ABSTRACT: The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.

SUBMITTER: Canovas S

PROVIDER: S-EPMC5340525 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.

Canovas Sebastian S Ivanova Elena E Romar Raquel R García-Martínez Soledad S Soriano-Úbeda Cristina C García-Vázquez Francisco A FA Saadeh Heba H Andrews Simon S Kelsey Gavin G Coy Pilar P

eLife 20170201

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive ...[more]

PMID: 28134613

Similar Datasets

Project description:BackgroundAssisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother-father-newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa). To verify our results from the MoBa cohort, we used an external cohort of 149 ART and 58 non-ART neonates from the Australian 'Clinical review of the Health of adults conceived following Assisted Reproductive Technologies' (CHART) study. The Illumina EPIC array was used to measure DNAm in both datasets. In the MoBa cohort, we performed a set of X-chromosome-wide association studies ('XWASs' hereafter) to search for sex-specific DNAm differences between ART and non-ART newborns. We tested several models to investigate the influence of various confounders, including parental DNAm. We also searched for differentially methylated regions (DMRs) and regions of co-methylation flanking the most significant CpGs. Additionally, we ran an analogous model to our main model on the external CHART dataset.ResultsIn the MoBa cohort, we found more differentially methylated CpGs and DMRs in girls than boys. Most of the associations persisted after controlling for parental DNAm and other confounders. Many of the significant CpGs and DMRs were in gene-promoter regions, and several of the genes linked to these CpGs are expressed in tissues relevant for both ART and sex (testis, placenta, and fallopian tube). We found no support for parental DNAm-dependent features as an explanation for the observed associations in the newborns. The most significant CpG in the boys-only analysis was in UBE2DNL, which is expressed in testes but with unknown function. The most significant CpGs in the girls-only analysis were in EIF2S3 and AMOT. These three loci also displayed differential DNAm in the CHART cohort.ConclusionsGenes that co-localized with the significant CpGs and DMRs associated with ART are implicated in several key biological processes (e.g., neurodevelopment) and disorders (e.g., intellectual disability and autism). These connections are particularly compelling in light of previous findings indicating that neurodevelopmental outcomes differ in ART-conceived children compared to those naturally conceived.

Project description:Societal changes and the increasing desire and opportunity to preserve fertility have increased the demand for effective assisted reproductive technologies (ART) and have increased the range of scenarios in which ART is now used. In recent years, the "freeze-all" strategy of cryopreserving all oocytes or good quality embryos produced in an IVF cycle to transfer later-at a time that is more appropriate for reasons of medical need, efficacy, or desirability-has emerged as an accepted and valuable alternative to fresh embryo transfer. Indeed, improvements in cryopreservation techniques (vitrification) and the development of more efficient ovarian stimulation protocols have facilitated a dramatic increase in the practice of elective frozen embryo transfer (eFET). Alongside these advances, debate continues about whether eFET should be a standard treatment option available to the whole IVF population or if it is important to identify patient subgroups who are most likely to benefit from such an approach. Achieving successful outcomes in ART, whether by fresh or frozen embryo transfer, is influenced by a wide range of factors. As well as the efficiency of IVF and embryo transfer protocols and techniques, factors affecting implantation include maternal aging, sperm quality, the vaginal and endometrial microbiome, and peri-implantation levels of serum progesterone. The safety of eFET, both during ART cycles and on longer-term obstetric and neonatal outcomes, is also an important consideration. In this review, we explore the benefits and risks of freeze-all strategies in different scenarios. We review available evidence on the outcomes achieved with elective cryopreservation strategies and practices and how these compare with more traditional IVF cycles with fresh embryo transfers, both in the general IVF population and in subgroups of special interest. In addition, we consider how to optimize and individualize "freeze-all" procedures to achieve successful reproductive outcomes.

Project description:BACKGROUND:Over the last several decades, the average age of first-time mothers has risen steadily. With increasing maternal age comes a decrease in fertility, which in turn has led to an increase in the use of assisted reproductive technologies by these women. Assisted reproductive technologies (ARTs), including superovulation and embryo culture, have been shown separately to alter imprinted DNA methylation maintenance in blastocysts. However, there has been little investigation on the effects of advanced maternal age, with or without ARTs, on genomic imprinting. We hypothesized that ARTs and advanced maternal age, separately and together, alter imprinted methylation in mouse preimplantation embryos. For this study, we examined imprinted methylation at three genes, Snrpn, Kcnq1ot1, and H19, which in humans are linked to ART-associated methylation errors that lead to imprinting disorders. RESULTS:Our data showed that imprinted methylation acquisition in oocytes was unaffected by increasing maternal age. Furthermore, imprinted methylation was normally acquired when advanced maternal age was combined with superovulation. Analysis of blastocyst-stage embryos revealed that imprinted methylation maintenance was also not affected by increasing maternal age. In a comparison of ARTs, we observed that the frequency of blastocysts with imprinted methylation loss was similar between the superovulation only and the embryo culture only groups, while the combination of superovulation and embryo culture resulted in a higher frequency of mouse blastocysts with maternal imprinted methylation perturbations than superovulation alone. Finally, the combination of increasing maternal age with ARTs had no additional effect on the frequency of imprinted methylation errors. CONCLUSION:Collectively, increasing maternal age with or without superovulation had no effect of imprinted methylation acquisition at Snrpn, Kcnq1ot1, and H19 in oocytes. Furthermore, during preimplantation development, while ARTs generated perturbations in imprinted methylation maintenance in blastocysts, advanced maternal age did not increase the burden of imprinted methylation errors at Snrpn, Kcnq1ot1, and H19 when combined with ARTs. These results provide cautious optimism that advanced maternal age is not a contributing factor to imprinted methylation errors in embryos produced in the clinic. Furthermore, our data on the effects of ARTs strengthen the need to advance clinical methods to reduce imprinted methylation errors in in vitro-produced embryos.

Dataset Information

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.

Publications

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets