Higher Incidence of Embryonic Defects in Mouse Offspring Conceived with Assisted Reproduction from Fathers with Sperm Epimutations
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ABSTRACT:
PROVIDER: PRJNA983347 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24911828_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911828_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911829_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911829_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911830_1.fastq.gz | Fastqsanger.gz |
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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
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.
2019-07-29 | GSE131433 | GEO
Project description:Children conceived using Assisted Reproductive Technologies (ART) have a higher incidence of growth and birth defects, attributable in part to epigenetic perturbations. Both ART and germline defects associated with parental infertility could interfere with epigenetic reprogramming events in germ cells or early embryos. Mouse models indicate that the placenta is more susceptible to the induction of epigenetic abnormalities than the embryo, and thus the placental methylome may provide a sensitive indicator of ‘at risk’ conceptuses. Our goal was to use genome-wide profiling to examine the extent of epigenetic abnormalities in matched placentas from an ART/infertility group and control singleton pregnancies (n=44/group) from a human prospective longitudinal birth cohort, the 3D Study. Principal component analysis revealed a group of ART outliers. The ART outlier group was enriched for females and a subset of placentas showing loss of methylation of several imprinted genes including GNAS, SGCE, KCNQT1OT1 and BLCAP/NNAT. Within the ART group, placentas from pregnancies conceived with IVF/ICSI showed distinct epigenetic profiles as compared to those conceived with less invasive procedures (ovulation induction, intrauterine insemination). Male factor infertility and paternal age further differentiated the IVF/ICSI group, suggesting an interaction of infertility and techniques in perturbing the placental epigenome. Together, the results suggest that the human placenta is sensitive to the induction of epigenetic defects by ART and/or infertility, and we stress the importance of considering both sex and paternal factors and that some but not all ART conceptuses will be susceptible.
2018-10-01 | GSE120250 | GEO
Project description:Epigenome-wide Association study of individuals conceived by Assisted Reproduction Technologies at birth and adulthood
| PRJNA543534 | ENA
Project description:Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to jet fuel (Jip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Jip1/Cip1, Jip2/Cip2, and Jip3/Cip3), resulting in three arrays for the treatment.
2014-07-22 | E-GEOD-59553 | biostudies-arrayexpress
Project description:Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a M-bM-^@M-^\pesticide mixtureM-bM-^@M-^] (pesticide permethrin and insect repellent N,N-Diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to pesticides (Pip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Pip1/Cip1, Pip2/Cip2, and Pip3/Cip3), resulting in three arrays for the treatment.
2014-07-22 | E-GEOD-59554 | biostudies-arrayexpress
Project description:Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.
2014-07-22 | GSE59553 | GEO
Project description:Epigenetic inheritance is the transmission of altered gene expression states across dividing cells without DNA sequence variation. Induced epigenetic changes (epimutations) have been extensively studied, but importantly, epimutations also occur spontaneously in a manner reminiscent of DNA sequence change. Small RNAs are established as a source of spontaneous epimutations which transmit gene expression changes over multiple generations in C.elegans. These changes are generally short lived, but rarely long-lived changes occur. Given that chromatin state is a critical regulator of gene expression, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational epigenetic inheritance. We compared the chromatin profiles and gene expression profiles at matched time points from a twenty generation bottlenecked lineage of C.elegans. We found that heritable changes in gene expression arose at a higher rate than the estimate for DNA sequence variation, indicating that these were true epigenetic events. In addition to recapitulating the known role for small RNAs, we provide evidence for chromatin mediated epimutations as an alternative mechanism driving epigenetic inheritance. Chromatin epimutations were heritable, enriched in the germline and synchronised with inherited gene expression changes. As with small RNA mediated epimutations, they were generally short lived with a tendency to resolve to baseline after 2-3 generations. A subset of chromatin epimutations however were long lasting, and these were uniquely enriched in piRNA clusters. Genes with long lived epimutations were implicated in multiple components of xenobiotic response pathways. This points to a mechanism for epigenetic ‘anticipation’ of environmental stressors. Adaptive traits driven by epimutations may be selected for under adverse conditions and lost on return to normal conditions, enabling soft adaptation in the absence of genetic sequence change.
2023-01-08 | GSE211846 | GEO
Project description:H3K27me3 demethylases and epimutations
| PRJEB36508 | ENA
Project description:PurposeTo examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital deliveries.MethodsWe conducted a retrospective cohort study using medical health records of deliveries occurring in 2016-2022 at a women's specialty hospital in a southern state of the Unites States (US). Pregnancies achieved using medically assisted reproductive (MAR) techniques were compared with unassisted pregnancies using propensity score matching (PSM), based on demographic, preexisting health, and reproductive factors. Study outcomes included cesarean delivery, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), delivery complications, and postpartum readmission. We used Poisson regression with robust standard errors to generate risk ratios (RRs) and 95% confidence intervals (CIs) for all study outcomes.ResultsAmong 57,354 deliveries, 586 (1.02%) pregnancies were achieved using MAR and 56,768 (98.98%) were unassisted ("non-MAR"). Compared to the non-MAR group, MAR pregnancies had significantly higher prevalence of all study outcomes, including GDM (15.9% vs. 11.2%, p < 0.001), HDP (28.2% vs. 21.1%, p < 0.001), cesarean delivery (56.1% vs. 34.6%, p < 0.001), delivery complications (10.9% vs. 6.8%, p = 0.03), and postpartum readmission (4.3% vs. 2.7%, p = 0.02). In a PSM sample of 584 MAR and 1,727 unassisted pregnancies, MAR was associated with an increased risk of cesarean delivery (RR = 1.11, 95% CI = 1.01-1.22); whereas IVF was associated with an increased risk of cesarean delivery (RR = 1.15, 95% CI = 1.03-1.28) and delivery complications (RR = 1.44, 95% CI = 1.04-2.01).ConclusionsWomen who conceived with MAR were at increased risk of cesarean deliveries, and those who conceived with IVF were additionally at risk of delivery complications.
| S-EPMC10957823 | biostudies-literature