Differentially expressed tRNA-derived fragments in bovine fetuses with assisted reproduction induced congenital overgrowth syndrome
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PROVIDER: PRJNA881298 | ENA |
REPOSITORIES: ENA
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Project description:Background: As couples struggle with infertility and livestock producers wish to rapidly improve genetic merit in their herd, assisted reproductive technologies (ART) have become increasingly popular in human medicine as well as the livestock industry. Utilizing ART can cause an increased risk of congenital overgrowth syndromes, such as Large Offspring Syndrome (LOS) in ruminants. A dysregulation of transcripts has been observed in bovine fetuses with LOS, which is suggested to be a cause of the phenotype. Our recent study identified variations in tRNA expression in LOS individuals, leading us to hypothesize that variations in tRNA expression can influence the availability of their processed regulatory products, tRNA-derived fragments (tRFs). Due to their resemblance in size to microRNAs, studies suggest that tRFs target mRNA transcripts and regulate gene expression. Thus, we have sequenced small RNA isolated from skeletal muscle and liver of day 105 bovine fetuses to elucidate the mechanisms contributing to LOS. Moreover, we have utilized our previously generated tRNA sequencing data to analyze the contribution of tRNA availability to tRF abundance. Results: 22,289 and 7,737 unique tRFs were predicted in the liver and muscle tissue respectively. The greatest number of reads originated from 5′ tRFs in muscle and 5′ halves in liver. In addition, mitochondrial (MT) and nuclear derived tRF expression was tissue-specific with most MT-tRFs and nuclear tRFs derived from LysUUU and iMetCAU in muscle, and AsnGUU and GlyGCC in liver. Despite variation in tRF abundance within treatment groups, we identified differentially expressed (DE) tRFs across Control-AI, ART-Normal, and ART-LOS groups with the most DE tRFs between ART-Normal and ART-LOS groups. Many DE tRFs target transcripts enriched in pathways related to growth and development in the muscle and tumor development in the liver. Finally, we found positive correlation coefficients between tRNA availability and tRF expression in muscle (R = 0.47) and liver (0.6). Conclusion: Our results highlight the dysregulation of tRF expression and its regulatory roles in LOS. These tRFs were found to target both imprinted and non-imprinted genes in muscle as well as genes linked to tumor development in the liver. Furthermore, we found that tRNA transcription is a highly modulated event that plays a part in the biogenesis of tRFs. This study is the first to investigate the relationship between tRNA and tRF expression in combination with ART-induced LOS.
2022-11-15 | GSE213525 | GEO
Project description:Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith-Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ART-induced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day 105 Bos taurus indicus X Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI when compared to controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between bodyweight and the number of biallelically expressed imprinted genes in LOS fetuses. Further, not only was there loss of allele-specific expression of imprinted genes in LOS, but we also observed differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovine and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multi-locus loss-of-imprinting syndrome, as is BWS.
2015-03-06 | GSE63509 | GEO
Project description:Background: As couples struggle with infertility and livestock producers wish to rapidly improve genetic merit in their herd, assisted reproductive technologies (ART) have become increasingly popular in human medicine as well as the livestock industry. Utilizing ART can cause an increased risk of congenital overgrowth syndromes, such as Large Offspring Syndrome (LOS) in ruminants. A dysregulation of transcripts has been observed in bovine fetuses with LOS, which is suggested to be a cause of the phenotype. Our recent study identified variations in tRNA expression in LOS individuals, leading us to hypothesize that variations in tRNA expression can influence the availability of their processed regulatory products, tRNA-derived fragments (tRFs). Due to their resemblance in size to microRNAs, studies suggest that tRFs target mRNA transcripts and regulate gene expression. Thus, we have sequenced small RNA isolated from skeletal muscle and liver of day 105 bovine fetuses to elucidate the mechanisms contributing to LOS. Moreover, we have utilized our previously generated tRNA sequencing data to analyze the contribution of tRNA availability to tRF abundance. Results: 22,289 and 7,737 unique tRFs were predicted in the liver and muscle tissue respectively. The greatest number of reads originated from 5' tRFs in muscle and 5' halves in liver. In addition, mitochondrial (MT) and nuclear derived tRF expression was tissue-specific with most MT-tRFs and nuclear tRFs derived from LysUUU and iMetCAU in muscle, and AsnGUU and GlyGCC in liver. Despite variation in tRF abundance within treatment groups, we identified differentially expressed (DE) tRFs across Control-AI, ART-Normal, and ART-LOS groups with the most DE tRFs between ART-Normal and ART-LOS groups. Many DE tRFs target transcripts enriched in pathways related to growth and development in the muscle and tumor development in the liver. Finally, we found positive correlation coefficients between tRNA availability and tRF expression in muscle (R = 0.47) and liver (0.6). Conclusion: Our results highlight the dysregulation of tRF expression and its regulatory roles in LOS. These tRFs were found to target both imprinted and non-imprinted genes in muscle as well as genes linked to tumor development in the liver. Furthermore, we found that tRNA transcription is a highly modulated event that plays a part in the biogenesis of tRFs. This study is the first to investigate the relationship between tRNA and tRF expression in combination with ART-induced LOS.
| S-EPMC9705782 | biostudies-literature
Project description:Effect of assisted reproduction on maternal immune cells
| PRJNA923713 | ENA
Project description:Assisted reproductive therapies (ART) have become increasingly common worldwide and up to ~6% of children currently born in developed countries were conceived employing these technologies. Numerous retrospective studies have suggested that ART-conceived children are more likely to develop the overgrowth syndrome Beckwith-Wiedemann (BWS). In bovine, the use of ART can induce a similar overgrown condition, which is referred to as large offspring syndrome (LOS). Both BWS and LOS involve dysregulation of imprinted genes. However, it remains largely unknown whether aberrant gene expression and DNA methylation occur at non-imprinted loci and to what extent these molecular alterations can contribute to these syndromes. Here we examined the transcriptome of skeletal muscle, liver, kidney, and brain of control and LOS bovine fetuses and found that different LOS fetuses exhibit different severity of the transcriptome alterations and different tissues have distinct gene pathways disturbed in LOS fetuses. Particularly for skeletal muscle, multiple pathways involved in myoblast proliferation and fusion into myotubes are misregulated in LOS fetuses. Further, characterization of the methylome of skeletal muscle demonstrates numerous local methylation differences; however, global DNA methylation is comparable between all individuals regardless of bodyweight. Importantly, only a small percent of differentially expressed genes (DEGs) including the imprinted gene IGF2R can be linked to the neighboring differentially methylated regions (DMRs). In summary, we not only show that misregulation of non-imprinted genes in addition to loss-of-imprinting contributes to the ART-induced overgrowth syndrome but also demonstrate that most of the aberrant gene expression is not associated with DNA methylome epimutations.
2017-10-31 | GSE93775 | GEO
Project description:Impact of Assisted Reproduction, Infertility, Sex, and Paternal Factors on the Placental DNA Methylome
| PRJNA492305 | ENA
Project description:As part of an investigation on contributors to offspring size following assisted reproduction, we investigated fetal cord tissue DNA methylation at 281 CpGs previously associated with maternal pregnancy morbidity or offspring growth across various tissues. The Illumina HumanMethylation450 BeadChip was used to obtain DNA methylation profiles in previously frozen cord tissues samples from 69 assisted reproduction-conceived and 950 spotaneously conceived live births.
2020-09-15 | GSE157896 | GEO
Project description:Moderate maternal folic acid supplementation ameliorates adverse embryonic and epigenetic outcomes associated with assisted reproduction
| PRJNA507637 | ENA
Project description:Epigenome-wide Association study of individuals conceived by Assisted Reproduction Technologies at birth and adulthood
| PRJNA543534 | ENA
Project description:As part of an investigation on contributors to offspring size following assisted reproduction, we investigated maternal mid-/late-pregnancy peripheral blood buffy coat DNA methylation at 240 CpGs previously associated with maternal pregnancy morbidity or offspring growth across various tissues. Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles in previously frozen buffy coat samples from 70 women who conceived via assisted reproduction technologies and gave live births and 845 women who spotaneously conceived and gave live births.
2020-09-16 | GSE158063 | GEO