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Comparison of genome-wide DNA methylation profiles of human fetal tissues conceived by in vitro fertilization and natural conception

ABSTRACT: Comparison of genome-wide DNA methylation profiles of human fetal tissues conceived by in vitro fertilization and natural conception

PROVIDER: PRJNA670447 | ENA |

REPOSITORIES: ENA

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Hepatic RNA sequence in male mice offspring conceived by in-vitro Fertilization and Frozen-thawed Embryo Transfer

Project description:Our study reported an increased risk of metabolic disorders in in-vitro Fertilization and Frozen-thawed Embryo Transfer (IVF-FET) conceived offspring compared with those born after IVF-ET. To explore the underlying mechanisms of the aberrant metabolism in male offspring conceived by IVF and FET compared with natural conceived (NC), we performed the RNA-sequencing of livers from three groups. We performed GSEA analysis. The results suggested more severe alterations in the expression of genes involved in insulin resistance pathway in the FET-chow group than that in the IVF-chow group.

2021-01-15 | GSE164819 | GEO

Comparison of genome-wide DNA methylation profiles of human fetal tissues conceived by in vitro fertilization and natural conception

Project description:Genome wide DNA methylation profiling of fetal tissue from elective terminations of pregnancy and multifetal pregnancy reduction. The Illumina Infinium HumanMethylation 450k BeadChip array was used to obtain DNA methylation profiles across approximately 453,093 CpGs in fetal tissue samples.

2021-08-03 | GSE159769 | GEO

Differential gene expression during placentation in pregnancies conceived with different fertility treatments compared with spontaneous pregnancies

Project description:This SMAART cohort study uses bulk total RNA-sequencing to assses the impact of mode of conception on first trimester human placenta gene expression [PMID: 30611556]. Pregnancies were singleton, gestational age 10-14 weeks, normal karyotype, fetal race Caucasian or biracial Caucasian/Asian, and conceived either with fertility treatments (IVF=in vitro fertilization, NIFT=non-IVF fertility treatment) or without fertility treatments (spontaneous, also called unassisted). Pregnancies were balanced for fetal sex. Chorionic villi tissue leftover after clinical genetic testing was collected for research with informed consent and stored in RNAlater RNA Stabilization Reagent (QIAGEN) at -80C until RNA isolation with the AllPrep DNA/RNA Mini Kit (QIAGEN). RNA-seq libraries of >200 nt were constructed with Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kits (Illumina) and depleted of cytoplasmic and mitochondrial ribosomal RNAs. After quality check with FastQC, transcript abundances were quantified against the human reference genome (Ensembl build GRCh38) using Kallisto. Differential expression analysis with DESeq2 was performed to compare mode of conception, adjusted for fetal sex and RNA-seq dataset. The dataset adjustment corrected for batch effects from RNA isolation and/or sequencing runs. There were N=141 subjects total, including 74 spontaneous, 33 non-IVF (NIFT), and 34 IVF pregnancies. The subject columns at the end of the DESeq2 files are counts normalized for sequencing depth.

2022-10-18 | GSE215421 | GEO

In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages

Project description:Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF), its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis, a high number of embryos containing abnormal cells can pass this strong selection barrier. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF- and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF- and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.

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Higher Incidence of Embryonic Defects in Mouse Offspring Conceived with Assisted Reproduction from Fathers with Sperm Epimutations

Project description:Assisted reproductive technologies (ART) account for 1-6% of live births in developed countries. While most children conceived using ART are healthy, increases in birth and genomic imprinting defects have been reported; such abnormal outcomes have been attributed to underlying parental infertility and/or the ART used. Here, we assessed whether paternal genetic and lifestyle factors, that are associated with male infertility and affect the sperm epigenome, can influence ART outcomes. We examined how paternal factors, Dnmt3L haploinsufficiency and/or diet-induced obesity, in combination with ART (superovulation, in vitro fertilization, embryo culture and embryo transfer), could adversely influence embryo development and DNA methylation patterning in mice. While male mice fed high-fat diets (HFD) gained weight and showed perturbed metabolic health, their sperm DNA methylation was minimally affected by the diet. In contrast, Dnmt3L haploinsufficiency induced a marked loss of DNA methylation in sperm; notably, regions affected were associated with neurodevelopmental pathways and enriched in young retrotransposons, sequences that can have functional consequences in the next generation. Following ART, placental imprinted gene methylation and growth parameters were impacted by one or both paternal factors. For the embryos conceived by natural conception, the abnormality rates were similar for WT and Dnmt3L+/- fathers. In contrast, paternal Dnmt3L+/- genotype, as compared to WT fathers, resulted in a 3-fold increase in the incidence of morphological abnormalities in embryos generated by ART. Together, the results indicate that embryonic morphological and epigenetic defects associated with ART may be exacerbated in offspring conceived by fathers with sperm epimutations.

2023-12-05 | GSE234855 | GEO

Comparison of Genome-Wide DNA Methylation Profiles of Human Fetal Tissues Conceived by <i>in vitro</i> Fertilization and Natural Conception.

Project description:BackgroundAssisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring' later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET).ResultsGlobal methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5'UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B).ConclusionsART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.

| S-EPMC8318003 | biostudies-literature

Hepatic RNA sequence in male mice offspring conceived by in-vitro Fertilization and Frozen-thawed Embryo Transfer

Project description:Hepatic RNA sequence in male mice offspring conceived by in-vitro Fertilization and Frozen-thawed Embryo Transfer

| PRJNA692162 | ENA

Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer [RNA-seq]

Project description:Next generation sequencing was perfomed to identify differentially expressed gene in Placental tissue samples from IVF-ET assisted or natural conceived pregnancies

2021-10-21 | GSE186147 | GEO

Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer [miRNA-seq]

Project description:Next generation sequencing was perfomed to identify differentially expressed micro-RNA in Placental tissue samples from IVF-ET assisted or natural conceived pregnancies

2021-10-21 | GSE186148 | GEO

Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse

Project description:Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that contribute to the sex-specfic phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.

2021-09-01 | GSE158029 | GEO

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