Review: Large offspring syndrome in ruminants: current status and prediction during pregnancy

Nava-Trujillo, Héctor; Rivera, Rocío Melissa

doi:10.1016/j.animal.2023.100740

Cited by 9 publications

(4 citation statements)

References 67 publications

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“…Large offspring syndrome (LOS) has been reported in cloned animals, suggesting a possible association [ 2 , 41 ]. The occurrence and severity of LOS, one of the most common unexpected events in cloned fetuses, is closely related to embryo culture conditions [ 42 ]. LOS is a congenital overgrowth disorder influenced by multi-locus loss of imprinting; global dysregulation of small and long RNAs; and changes in DNA methylation and chromosomal architecture, which affect organ size, cell proliferation, and cell survival [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…The occurrence and severity of LOS, one of the most common unexpected events in cloned fetuses, is closely related to embryo culture conditions [ 42 ]. LOS is a congenital overgrowth disorder influenced by multi-locus loss of imprinting; global dysregulation of small and long RNAs; and changes in DNA methylation and chromosomal architecture, which affect organ size, cell proliferation, and cell survival [ 42 ]. During the early stages, when physical changes manifest rapidly, the body focuses on growth.…”

Section: Resultsmentioning

confidence: 99%

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Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

Woo,

Kim,

Kang

et al. 2024

Genes

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Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging. The substitutional signature of cloning-specific somatic mutations mirrored the uniform distribution characteristic of the signature associated with human aging. Further analysis of genes revealed significant enrichment of traits associated with body size as well as the molecular mechanisms underlying neuronal function and tumorigenesis. Overall, the somatic mutations found in cloned dogs may indicate a conserved mechanism driving aging across species and a broad spectrum of pathway alterations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

Woo,

Kim,

Kang

et al. 2024

Genes

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“…IVP calves demonstrated deviation from standard parameters, including excessive birth weights, higher body temperature within the first hour of life, and alteration in acid-base balance; one IVP calf had an enlarged umbilical cord, a problem of common occurrence in in vitro-produced calves (Batchelder et al, 2007). Indeed, although the reduction in the use of serum may reduce the incidence of LOS, developmental abnormalities have still been reported in concept derived from in vitro culture with no serum (Crosier et al, 2001;Miles et al, 2005;Nava-Trujillo & Rivera, 2023).…”

Section: Discussionmentioning

confidence: 99%

Analysis of physical traits, clinical parameters, and energy metabolism of in vivo‐ and in vitro‐derived Flemish newborn calves during the first day of life

Schütz,

Zago,

de Aguiar

et al. 2024

Reprod Domestic Animals

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Studies investigating physiological deviations from normality in newborn calves derived from in vitro fertilization procedures remain important for the understanding of factors that reduce calf survival after birth. The aim of this study was to investigate parameters affecting health and welfare of newborn Flemish calves derived from in vitro embryo production (IVP) in the first hours of life in comparison to in vivo‐derived calves. Physical traits of newborn calves and fetal membranes (FM) were recorded soon after birth. Newborn venous blood samples were collected at several time points within the first 24 h of life for analyses of energy substrates, electrolytes, blood gases, acid–base balance, blood chemistry, and haematology. A liver biopsy was taken within the first hour after birth for analysis of gene expression of key enzymes of the fructolytic and glycolytic pathways. Newborn IVP calves were heavier and larger at birth, which was associated with heavier FM. At several time points during the first 24 h of life, IVP‐derived calves had altered rectal temperature, blood gases, electrolyte concentrations, blood parameters for liver, kidney and muscle function, and acid–base balance, plasma lipid metabolism, and hemogram parameters. The relative mRNA abundances for triokinase and lactate dehydrogenase‐B were greater in IVP calves. In summary, IVP‐derived newborn calves were at higher risk of clinical problems after birth, which was markedly greater in heavier and larger calves. Such animals take longer to adapt to extrauterine life and should receive a special attention during the immediate neonatal period.

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“…BWS and LOS share a broad spectrum of clinical features including macrosomia, macroglossia, abdominal wall defects (umbilical hernia/omphalocele), lateralized overgrowth, ear malformation, organomegaly, and placentomegaly [2,[7][8][9][10][11][12][13][14][15][16][17][18][19]. In addition, BWS is also associated with increased embryonal tumor incidence, hyperinsulinism, and facial nevus simplex [2], and LOS often results in dystocia and demise of offspring and dam due to offspring oversize [20]. BWS and LOS share epigenetic defects in the form of loss-of-imprinting at IGF2, KCNQ1, IGF2R, PLAGL1, PEG3, and DLK1 [2,[6][7][8][21][22][23][24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

The counterpart congenital overgrowth syndromes Beckwith-Wiedemann Syndrome in human and large offspring syndrome in bovine involve alterations in DNA methylation, transcription, and chromatin configuration

Li,

Xiao,

Boadu

et al. 2023

Preprint

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Beckwith-Wiedemann Syndrome (BWS, OMIM #130650) is a congenital epigenetic disorder in humans which affects approximately 1 in 10,340 children. The incidence is likely an underestimation as the condition is usually recognized based on observable phenotypes at birth. BWS children have up to a 28% risk of developing tumors and currently, only 80% of patients can be corroborated molecularly (epimutations/variants). It is unknown how the subtypes of this condition are molecularly similar/dissimilar globally, therefore there is a need to deeply characterize the syndrome at the molecular level. Here we characterize the methylome, transcriptome and chromatin configuration of 18 BWS individuals together with the animal model of the condition, the bovine large offspring syndrome (LOS). Sex specific comparisons are performed for a subset of the BWS patients and LOS. Given that this epigenetic overgrowth syndrome has been characterized as a loss-of-imprinting condition, parental allele-specific comparisons were performed using the bovine animal model. In general, the differentially methylated regions (DMRs) detected in BWS and LOS showed significant enrichment for CTCF binding sites. Altered chromosome compartments in BWS and LOS were positively correlated with gene expression changes, and the promoters of differentially expressed genes showed significant enrichment for DMRs, differential topologically associating domains, and differential A/B compartments in some comparisons of BWS subtypes and LOS. We show shared regions of dysregulation between BWS and LOS, including several HOX gene clusters, and also demonstrate that altered DNA methylation differs between the clinically epigenetically identified BWS patients and those identified as having DNA variants (i.e.CDKN1Cmicrodeletion). Lastly, we highlight additional genes and genomic regions that have the potential to serve as targets for biomarker development to improve current molecular methodologies. In summary, our results suggest that genome-wide alternation of chromosome architecture, which is partially caused by DNA methylation changes, also contribute to the development of BWS and LOS.

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Review: Large offspring syndrome in ruminants: current status and prediction during pregnancy

Cited by 9 publications

References 67 publications

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

Analysis of physical traits, clinical parameters, and energy metabolism of in vivo‐ and in vitro‐derived Flemish newborn calves during the first day of life

The counterpart congenital overgrowth syndromes Beckwith-Wiedemann Syndrome in human and large offspring syndrome in bovine involve alterations in DNA methylation, transcription, and chromatin configuration

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