Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA480201 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7497760.fastq.gz | Fastqsanger.gz | |||
| SRR7497770.fastq.gz | Fastqsanger.gz | |||
| SRR7497780.fastq.gz | Fastqsanger.gz | |||
| SRR7497790.fastq.gz | Fastqsanger.gz | |||
| SRR7497800.fastq.gz | Fastqsanger.gz |
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Project description:Genome wide DNA methylation profiling of whole blood at birth (Guthrie blood spots) and adulthood of individuals conceived by assisted reproductive technology (ART) and matched non-ART controls. The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in guthrie cards and whole adult blood.
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Project description:Assisted reproductive technology (ART) has become an indispensable tool in fertility treatment. Most ART patients respond normally to controlled ovarian stimulation, however some may benefit from the alternative method of oocyte in vitro maturation (IVM), recognized but still underdeveloped method with limited results. As oocytes undergo the transcriptionally silent phase of meiosis, protein synthesis is an important regulator of oocyte development. Here, we have modelled and compared the clinically relevant IVM simulation with in vivo conditions in mouse oocytes and zygotes.
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Project description:With the increasing use of Assisted Reproductive Technologies (ART) for treatment of human infertility, there is an increasing requirement for embryo culture conditions that perform as similar to nature as possible. How good the match, however, cannot be tested experimentally in human. We solved the central question of how well ART culture protocols prepare embryos for postimplantation development, under the provisions of the 'mouse embryo assay' (MEA). Our side-by-side comparison of 8 conditions [i.e., 3 culture conditions (KSOM, HTF and ISDM1) plus the in vivo system in two different mouse strains (B6 and CD1)] shows that mouse embryos cultured under ART conditions are differentially primed for postimplantation development, and that certain ART protocols outperform the oviduct. The distinct performances of blastocysts formed in ART vs. oviduct do not correlate with any significant transcriptome changes, whereas protein analysis by immunoconfocal microscopy reveals differences in the allocation of embryonic cells to the three germ layers of blastocysts. We conclude that in vitro technology is not always a defective copy of nature, and that the choice of ART protocol primes the embryos for subsequent development. 22 samples were analyzed. B6KSOM: Mouse B6 background, E3.5 blastocysts in KSOM medium, 3 biological rep B6HTF: Mouse B6 background, E3.5 blastocysts in HTF medium, 3 biological rep B6ISM1: Mouse B6 background, E3.5 blastocysts in ISM1 medium, 3 biological rep B6vivo: Mouse B6 background, E3.5 blastocysts in vivo, 3 biological rep CD1KSOM: Mouse CD1 background, E3.5 blastocysts in KSOM medium, 1 biological rep CD1HTF: Mouse CD1 background, E3.5 blastocysts in HTF medium, 3 biological rep CD1ISM1: Mouse CD1 background, E3.5 blastocysts in ISM1 medium, 3 biological rep CD1vivo: Mouse CD1 background, E3.5 blastocysts in vivo, 3 biological rep
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Project description:Placental abnormalities are associated with type of embryo transfer in assisted reproductive technologies (ART)
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Project description:Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture in vitro to produce offspring. ART pregnancies have increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. We and others have previously shown that embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. We hypothesized that these adverse effects are linked to a subtle disruption of specific biological processes during preimplantation development. To test this hypothesis, we performed embryo culture for several discrete periods of preimplantation development and assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio in two distinct windows of preimplantation embryo development, while placental morphological abnormalities and reduced imprinting control region methylation were associated with culture prior to the morula stage. We also provide evidence that extended culture to the blastocyst stage induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and that female concepti exhibited a higher loss of DNA methylation than males. Altogether, this study identifies specific developmental windows of susceptibility and potential targets for embryo culture optimization.
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Project description:Assisted reproductive technology (ART) is an important part of reproductive medicine that comprises superovulation, in vitro fertilization (IVF), in vitro culture of embryos, cryopreservation and embryo transfer. Because it occurs in the sensitive period of gametogenesis and early embryonic development, its possible health effects on the offspring have received widespread attention in recent years. Relevant studies, though, are limited to postnatal follow-up and blood sample analysis. In this study, a mouse model was used to explore the effect of ART on gene expression in the organs of the off-spring using next-generation sequencing. The results showed that it caused abnormal expression in 1060 and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and cardiovascular system development is also enriched. STRING analysis identified Ccl2, Ptgs2, Rock1, MAPK14, Agt, Wnt5a as core interaction factors. DEGs in the spleen are significantly enriched in anti-infection and im-mune responses and in the hematopoiesis-related pathway "hematopoietic cell lineage", which includes the core factors Fos, Jun and Il1r2. Then, we explored the effects of ART on epigenetic modifiers and imprinted genes. The results showed that 42 heart genes and 5 spleen genes were abnormally expressed, most of which were related to histone modification and chromatin remodeling. Imprinted genes are very important for normal fetal and individual growth and development. It was found that the expression of imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the heart of ART offspring, and the DNA methylation levels of Igf2 and Mest imprinting control regions (ICRs) increased abnormally. Therefore, we con-cluded that, in the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring, causing potentially adverse effects on organ function. The results of this study can provide a reference for evaluating the safety of human ART and helping improve the clinical system.
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