Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Animal Reproduction

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ISSN: 19843143
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Início Publicação: 31/07/2004
Periodicidade: Trimestral
Área de Estudo: Medicina Veterinária

Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Ano: 2010 | Volume: 7 | Número: 3
Autores: L.C. Smith, J. Suzuki Jr., A.K. Goff, F. Filion, J. Therrien, B.D. Murphy, H.R. Kohan-Ghadr, R. Lefebvre, A.C. Brisville, S. Buczinski, G. Fecteau, F. Perecin, F.V. Meirelles
Autor Correspondente: L C Smith | [email protected]

Palavras-chave: cattle, cloning, embryos, epigenetics, imprinting

Resumos Cadastrados

Resumo Inglês:

Many of the developmental anomalies
observed in cloned animals are related to fetal and
placental overgrowth, a phenomenon known as the
“large offspring syndrome” (LOS) in ruminants. It has
been hypothesized that the epigenetic control of
imprinted genes, i.e. genes that are expressed in a
parental-specific manner, is at the root of LOS. Our
recent research has focused on understanding the
epigenetic alterations to imprinted genes that are
associated with assisted reproductive technologies
(ART), such as early embryo in vitro culture (IVC) and
somatic cell nuclear transfer (SCNT) in cattle. We have
searched and identified single nucleotide
polymorphisms in Bos indicus DNA useful for analysis
of parental-specific alleles and their respective
transcripts in tissues from hybrid embryos derived by
crossing Bos indicus and Bos taurus cattle. Due to the
frequency of placental anomalies in SCNT and in some
IVC gestations, our initial studies focused on genes
known to be necessary for trophoblast proliferation
(Mammalian Achaete Scute-like Homologue 2; ASCL2)
and differentiation (Heart and neural crest cell
derivative 1; HAND1). ASCL2 was bi-allelically
expressed prior to implantation but paternally silenced
after implantation. At day 17, SCNT embryos showed
more abundant ASCL2 and less abundant HAND1
transcripts. After implantation, SCNT fetal cotyledons
displayed higher ASCL2 and HAND1 than AI and IVC
tissues. To further investigate epigenetic anomalies, we
analyzed the differentially methylated regions of other
imprinted genes in cattle, i.e. SNRPN, H19 and the
IGF2R. Compared with the patterns observed in vivo
(AI), we observed a generalized hypomethylation of the
imprinted allele and the bi-allelic expression of embryos
produced by SCNT. Together, these results indicate that
imprinting marks are erased during the reprogramming
of the somatic cell nucleus during early development,
indicating that such epigenetic anomalies may play a
key role in the mortality and morbidity of cloned
animals.