Aberrant CpG methylation of the imprinting control region KvDMR1 detected in assisted reproductive technology-produced calves and pathogenesis of large offspring syndrome

Hori, Noboru; Nagai, Makoto; Hirayama, Muneyuki; Hirai, Tomokazu; Matsuda, Keisuke; Hayashi, Michiko; Tanaka, Takaichi; Ozawa, Tadashi; Horike, Shin-ichi

doi:10.1016/j.anireprosci.2010.09.008

Cited by 60 publications

(58 citation statements)

References 54 publications

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“…Instead, Chen Cárdenas et al (2013) found a loss of imprinting leading to biallelic expression of KCNQ1OT1 (KCNQ1 oppositie strand/ antisense transcript 1, the gene most misregulated in BWS) in bovine LOS fetuses derived from IVP embryos, and that this is associated with a loss of methylation at the KvDMR1 (KCNQ1 differentially methylated region 1) on the maternal allele. This observation confirmed an earlier report of abnormal hypomethylation of KvDMR1 and expression of KCNQ1OT1 in two of seven SCNT cloned calves and one of two IVP-derived calves (Hori et al 2010). Although generally highly conserved, there are also recognisable differences in imprinting within eutherian mammals that could account for many such differences between species, differential imprinting at the IGF2R locus being a case in point (Das et al 2009;Renfree et al 2013).…”

Section: Epigenetic Programming Of Long-term Developmentsupporting

confidence: 78%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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Section: Epigenetic Programming Of Long-term Developmentsupporting

confidence: 78%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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“…Studies in animals have shown that certain aspects of assisted reproductive technology (ART) may induce imprinting errors that are maintained throughout fetal development (8) and/or postnatally (9) in ART offspring; however, the potential of propagating such epimutations to subsequent generations has not been thoroughly investigated. Secondary epimutations would be expected to be transmitted according to Mendelian inheritance patterns because of genetic transmission of the mutation that led to the observed epigenetic abnormalities, however, primary epimutations would potentially be corrected by germ-line-specific epigenetic reprogramming and, therefore, not transmitted to subsequent generations.…”

mentioning

confidence: 99%

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Waal

Yamazaki

Ingale

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The use of assisted reproductive technologies (ART) has become increasingly common worldwide and is now responsible for 2-3% of children born in developed countries. Multiple reports have suggested that ART-conceived children are more likely to develop rare epigenetic disorders such as Beckwith-Wiedemann Syndrome or Angelman Syndrome, both of which involve dysregulation of imprinted genes. Anecdotal reports suggest that animals produced with ART that manifest apparent epigenetic defects typically do not transmit these epimutations to subsequent generations when allowed to breed naturally, but this hypothesis has not been directly studied. We analyzed allele-specific DNA methylation and expression at three imprinted genes, H19, Snrpn, and Peg3, in somatic cells from adult mice generated with the use of intracytoplasmic sperm injection (ICSI), a type of ART. Epimutations were detected in most of the ICSI-derived mice, but not in somatic cells of their offspring produced by natural mating. We examined germ cells from the ICSI mice that exhibited epimutations in their somatic cells and confirmed normal epigenetic reprogramming of the three imprinted genes analyzed. Collectively, these results confirm that ART procedures can lead to the formation of primary epimutations, but while such epimutations are likely to be maintained indefinitely in somatic cells of the ART-derived individuals, they are normally corrected in the germ line by epigenetic reprogramming and thus, not propagated to subsequent generations.gametogenesis | transgenerational inheritance E arly embryos and germ cells are unique in that they must undergo extensive epigenetic reprogramming to reestablish developmental potency during each generation. This reprogramming entails erasure of most inherited epigenetic modifications followed by the acquisition and subsequent maintenance of new epigenetic profiles (1). Genomic imprinting is an epigenetic phenomenon found in eutherian and metatherian mammals (2) that results in parent-of-origin-specific, monoallelic expression of a subset of genes (3). This functional asymmetry of imprinted genes is conferred through differential DNA methylation patterns established during gametogenesis in each parent that distinguish the maternal and paternal alleles in the ensuing offspring (4, 5). These regions are known as differentially methylated regions (DMRs), and the differential methylation profiles at these genetic elements play an important role in regulating allele-specific expression of imprinted genes (3).Because the epigenome is distinct in each cell type and is readily reversible by developmental reprogramming, it is particularly susceptible to disruption by environmental influences (6). Such epigenetic defects are known as "epimutations" and can be of two types-primary epimutations or secondary epimutations (7). Primary epimutations result from a direct disruption of an epigenetic parameter such as DNA methylation that is then propagated through DNA replication to subsequent cells. Secondary epimutations result...

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“…For example, it has been known for a number of years that cows and sheep produced through IVF display an increased frequency of large offspring syndrome (LOS), characterized by numerous abnormalities including immunological defects, increased fetal/neonatal death, increased birth weight, organomegaly, and skeletal and placental defects (Behboodi et al, 1995;Young, Sinclair, & Wilmut, 1998). The phenotypes observed in LOS are similar to those observed in BWS and significantly, epigenetic abnormalities of the same loci involved in BWS are observed in calves and sheep with LOS: KCNQ10T1 is hypomethylated with a corresponding increase in KCNQ10T1 expression and decrease in CDKN1C expression (Hori et al, 2010); and LOS sheep also exhibit loss of imprinting for the IGF2 gene (Young et al, 2001). The similarities in IVF-induced epigenetic errors between humans and animal models, where subfertility is not a confounding issue, suggest that manipulation of the early embryo can lead to epigenetic perturbations with potential long-term consequences for offspring (Paolini-Giacobino, 2007;Velker et al, 2012).…”

Section: Ivf and Epigeneticsmentioning

confidence: 59%

Cytoplasmic Inheritance Redux

Charney¹

2013

Advances in Child Development and Behavior

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Aberrant CpG methylation of the imprinting control region KvDMR1 detected in assisted reproductive technology-produced calves and pathogenesis of large offspring syndrome

Cited by 60 publications

References 54 publications

Epigenetics and developmental programming of welfare and production traits in farm animals

Epigenetics and developmental programming of welfare and production traits in farm animals

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Cytoplasmic Inheritance Redux

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