Massive deregulation of miRNAs from nuclear reprogramming errors during trophoblast differentiation for placentogenesis in cloned pregnancy.
BACKGROUND
Low efficiency of Somatic Cell Nuclear Transfer (NT) has been widely addressed with high incidence of placental abnormalities due to genetic and epigenetic modifications. MiRNAs are shown to be major regulators of such modifications. The present study has been carried out to identify the expression patterns of 377 miRNAs, their functional associations and mechanism of regulation in bovine placentas derived from artificial insemination (AI), in vitro production (IVP) and NT pregnancies.


RESULTS
This study reveals a massive deregulation of miRNAs as chromosomal cluster or miRNA families without sex-linkage in NT and in-vitro derived IVP placentas. Cell specific localization miRNAs in blastocysts and expression profiling of embryos and placentas at different developmental stages identified that the major deregulation of miRNAs exhibited in placentas at day 50 of pregnancies is found to be less dependent on global DNA methylation, rather than on aberrant miRNA biogenesis molecules. Among them, aberrant AGO2 expression due to hypermethylation of its promoter was evident. Along with other factors, aberrant AGO2 expression was observed to be associated with multiple defects in trophoblast differentiation through deregulation of miRNAs mediated mechanisms.


CONCLUSIONS
These aberrant miRNA activities might be associated with genetic and epigenetic modifications in abnormal placentogenesis due to maldifferentiation of early trophoblast cell lineage in NT and IVP pregnancies. This study provides the first insight into genome wide miRNA expression, their role in regulation of trophoblast differentiation as well as abnormal placental development in Somatic Cell Nuclear Transfer pregnancies to pave the way to improve the efficiency of cloning by nuclear transfer.
Md Munir
MM
Hossain
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany. tesfaye@itw.uni-bonn.de.
Dawit
D
Tesfaye
Dessie
D
Salilew-Wondim
Eva
E
Held
Maren J
MJ
Pröll
Franca
F
Rings
Gregor
G
Kirfel
Christian
C
Looft
Ernst
E
Tholen
Jasim
J
Uddin
Karl
K
Schellander
Michael
M
Hoelker
D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D018899:CpG Islands; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering