Vascular Alterations Underlie Developmental Problems Manifested in Cloned Cattle before or after Birth

Maiorka, Paulo César; Favaron, Phelipe Oliveira; Mess, Andrea; Santos, Caio Rodrigues dos; Alberto, Miryan Lança Vilia; Meirelles, Flávio Vieira; Miglino, María Angélica

doi:10.1371/journal.pone.0106663

Cited by 12 publications

(17 citation statements)

References 45 publications

(72 reference statements)

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“…In agreement with previous studies2829, we observed important histological lesions in pathological cloned foetuses which included steatosis and severe fibrosis. In addition, we found that the fibrotic livers contained pseudo-canals of small hepatocytes reminiscent of regenerative nodules in cirrhotic livers.…”

Section: Discussionsupporting

confidence: 92%

“…The liver was selected for this study because it displays a grossly abnormal appearance (excessive size, enlarged lymphatic vessels, steatosis) at the necropsy of deceased clones2829, and is affected by deviations in the transcriptome30 and by DNA methylation defects at various developmental stages57. Furthermore, the liver plays a fundamental role in the metabolic transition to postnatal life, through its ability to synthesize, store and export nutrients such as glucose and lipids31.…”

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confidence: 99%

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Altered DNA methylation associated with an abnormal liver phenotype in a cattle model with a high incidence of perinatal pathologies

Kiefer

Jouneau

Campion

et al. 2016

Sci Rep

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Cloning enables the generation of both clinically normal and pathological individuals from the same donor cells, and may therefore be a DNA sequence-independent driver of phenotypic variability. We took advantage of cattle clones with identical genotypes but different developmental abilities to investigate the role of epigenetic factors in perinatal mortality, a complex trait with increasing prevalence in dairy cattle. We studied livers from pathological clones dying during the perinatal period, clinically normal adult clones with the same genotypes as perinatal clones and conventional age-matched controls. The livers from deceased perinatal clones displayed histological lesions, modifications to quantitative histomorphometric and metabolic parameters such as glycogen storage and fatty acid composition, and an absence of birth-induced maturation. In a genome-wide epigenetic analysis, we identified DNA methylation patterns underlying these phenotypic alterations and targeting genes relevant to liver metabolism, including the type 2 diabetes gene TCF7L2. The adult clones were devoid of major phenotypic and epigenetic abnormalities in the liver, ruling out the effects of genotype on the phenotype observed. These results thus provide the first demonstration of a genome-wide association between DNA methylation and perinatal mortality in cattle, and highlight epigenetics as a driving force for phenotypic variability in farmed animals.

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Altered DNA methylation associated with an abnormal liver phenotype in a cattle model with a high incidence of perinatal pathologies

Kiefer

Jouneau

Campion

et al. 2016

Sci Rep

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“…In our samples, we found the three vesicle types on day 32 of gestation, which is similar to the results previously described by Bryden et al (1972). Maiorka et al (2015) described in a 43-days-old bovine embryo the presence of prosencephalon, mesencephalon, and rhombencephalon. In the foetal stage, more complex nervous system development, including the formation of the choroid plexus and the initial ossification of the cranial region, was visible through our light microscopy analysis of toluidine blue-stained sections.…”

Section: Discussionsupporting

confidence: 91%

Macroscopic and microscopic analysis of 2 embryos and 1 foetus derived from a sheep (Ovis aries) without breed

Fernandes

Silva

Russo

et al. 2017

Braz. J. Vet. Res. Anim. Sci.

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The interest in embryology, the science of the development of a zygote into a completely developed foetus, has increased greatly in recent years due to a number of studies involving embryonic and induced pluripotent stem cells. In addition, the development of techniques such as cloning has aided to understand the critical events that occur during embryonic development. In this study, we describe the morphology of two sheep embryos and one foetus using macroscopic and microscopic techniques. We investigated sheep without defined breed on days 24, 32, and 50 of gestation (estimated by crown-rump length [CR]). Macroscopically, we observed the development of E1 (24 days), with visible optic vesicle, but without retinal pigmentation and the forelimbs bud in development. In the E2 (32 days), we noticed the presence of optic retinal pigmentation and forelimbs more developed in comparison with E1. As expected, F1 revealed an eyeball already covered and the forelimbs developed. Meanwhile, microscopic analysis revealed somite, ventricle, atrium, and oral cavity in development in E1. However, in F1 we were able to identify more complex structures, such as ossification in the spine, ventricle, atrium, intraventricular septum, pericardial sac, and oral cavity with tongue. This work brings more precise and detailed data on the morphological characteristics of the major organ systems (nervous, circulatory, respiratory, digestive, and urinary) at each embryonic and foetal stage analysed. Keywords: Embryology. Sheep. Embryos. Foetus. Embryonic development. ResumoO interesse em Embriologia, a ciência do desenvolvimento de um zigoto em um feto completamente desenvolvido, tem aumentado consideravelmente nos últimos anos devido a uma série de estudos envolvendo células-tronco pluripotentes embrionárias e induzidas. Além disso, o desenvolvimento de técnicas como a clonagem tem ajudado a compreender os eventos críticos que ocorrem durante o desenvolvimento embrionário. Neste estudo, descrevemos a morfologia de dois embriões de ovinos e um feto utilizando técnicas macroscópicas e microscópicas. Obtivemos ovelhas sem raça definida com 24, 32 e 50 dias de gestação (estimado pelo método de Crown-Rump, CR). Os conceptos foram mensurados, pesados e caracterizados a olho nu. Macroscopicamente, observamos o desenvolvimento dos embriões E1 (24 dias), apresentando globo ocular sem pigmentação de retina e broto do membro torácico e pélvico. Já o E2 (32 dias), apresentava globo ocular com pigmentação na retina e os membros torácicos e pélvicos mais desenvolvidos. O F1 apresentou olhos cobertos com uma membrana e membros torácicos e pélvicos mais desenvolvidos. Enquanto isso, microscopicamente observamos no E1 somitos, ventrículo, átrio e cavidade oral ainda em desenvolvimento. Porém, no F1 já era possível observar ossificação da coluna espinhal, coração com estruturas mais complexas, como ventrículo, átrio, septo interventricular e saco pericárdio. Além disso, na cavidade oral observamos a formação da língua. Este trabalho fornece informa...

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“…The correlation between PD‐US inexperience and higher risk of early pregnancy loss may reflect rough handling that damages the conceptus, perhaps through altered vascularization of placenta and other systems (Johnson, ; Maiorka et al., ), or through mechanical trauma to the heart (Abbitt et al., ; Franco, Drost, Thatcher, Shille, & Thatcher, ), which is located near the conceptus surface at days 28–35 of development (Pierson & Ginther, ). However, in this study, it is unlikely to be the main cause, based on the short average age of the cows diagnosed and the proper technique used to diagnose pregnancy (avoiding to retract the uterus).…”

Section: Discussionmentioning

confidence: 99%

Influence of practitioner expertise during early pregnancy diagnosis on pregnancy loss rate: A controlled, blinded trial

Patrón¹,

López-Helguera

Sebastián³

et al. 2017

Reprod Domestic Animals

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A controlled field trial was conducted to assess the potential influence of practitioner inexperience during early pregnancy diagnosis with ultrasound (PD-US) on the risk of pregnancy loss. A veterinarian with more than 10 years' experience in PD-US (Vet-A) and a veterinarian with fewer than 12 months' experience at the start of the study (Vet-B) visited the same dairy farm once a week for 33 and 26 weeks, respectively. The two veterinarians did not interact with each other at any time during the study, nor did they know that their data would later be used in this study. Using the same farm scanner, they performed PD-US at 28-34 day after breeding, together diagnosing 915 pregnancies. All cows were re-checked at 49-56 day after artificial insemination, and cows no longer pregnant were recorded as having suffered pregnancy loss. Although Vet-A and Vet-B diagnosed a similar proportion of pregnancies (58.44 ± 16% vs 56.96 ± 18%, p > .05), the rate of pregnancy loss was significantly higher among cows diagnosed by Vet-B (10.41 ± 11.2% vs 4.87 ± 9.0, p = .029). In addition, among cows diagnosed by Vet-B, the rate of pregnancy loss was significantly higher among cows diagnosed, while he had fewer than 12 months' PD-US experience (11.17 ± 12.14%) than among cows that he diagnosed later (7.14 ± 11.01%, p = .038); in fact, this latter loss rate was comparable to that among cows diagnosed by Vet-A during the same period (3.51 ± 9.83%, p = .620). These results suggest that inexperience with PD-US during the late embryonic period can increase risk of early pregnancy loss, supporting the need for proper training.

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Vascular Alterations Underlie Developmental Problems Manifested in Cloned Cattle before or after Birth

Cited by 12 publications

References 45 publications

Altered DNA methylation associated with an abnormal liver phenotype in a cattle model with a high incidence of perinatal pathologies

Altered DNA methylation associated with an abnormal liver phenotype in a cattle model with a high incidence of perinatal pathologies

Macroscopic and microscopic analysis of 2 embryos and 1 foetus derived from a sheep (Ovis aries) without breed

Influence of practitioner expertise during early pregnancy diagnosis on pregnancy loss rate: A controlled, blinded trial

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