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P.C .Cha havett ette-P e-Palmer almer, R.S.F. Lee ee, S. Camous amous, et al,. <strong>2011</strong>. The Placenta of Bovine Clones. fffffffffffffffffffffffffffffffffffffffffffffff ffffffff Acta Scientiae Veterinariae. 39(Suppl 1): s227 - s242. was found to be down-regulated [71]. Reduced expression of these three genes could mean that erythropoiesis could be impaired in the SCNT placenta and thus, compromise fetal survival. 4.5 Epigenetics and the role of imprinted genes Cloning by nuclear transfer returns a differentiated cell to a totipotent status, a process termed nuclear reprogramming, and was often associated with epigenetic alterations. Several studies have shown that insufficient epigenetic reprogramming of the differentiated nuclear donor cell towards a pluripotent (embryonic) status plays a major role in the pathogenesis of LOS [69]. Both global- and gene-specific DNA methylation has been studied in SCNT embryos and offspring of several species including mouse, pig, buffalo and cattle. In the early stages of development, a hypermethylation of the entire bovine embryo has been reported using immunostaining techniques, mainly revealing the methylation patterns of repetitive regions and heterochromatic regions of the genome [81]. Many of the pathologies reported with bovine clone pregnancies resemble abnormalities reported with either mutations or deletions of imprinted genes or dysregulation of imprinted gene expression. Embryo manipulations, such as assisted reproductive technology (ART), induce phenotypic changes in the embryo and the placenta by influencing imprinting genes, most of which being expressed in the placenta, in mouse [63], sheep [97] and human [4,34]. Studies in mouse mutants have shown that many of the genes involved in differentiation and growth of the placenta are imprinted [42,79]. Examples of imprinted genes which control placental growth include Igf2r [88], Igf2, Mash2 [39], Esx1 [61], Cdkn1c/p57 Kip2 [85] and Phlda2/Ipl/Tssc3 [35]. At the blastocyst stage, alteration of the epigenetic regulation of some imprinted genes is often associated with the embryo death. A loss of DMR methylation (differentially methylated regions implicated in the imprinting regulation) was found for IGF2R [62] and SNRPN [84] genes. In contrast, an overall lesser methylation in the DMR of the IGF2/H19 alleles was found in cattle when compared to the same tissues in control animals [37]. In the mouse, overexpression of Igf2 results in fetal and placental overgrowth and overgrowth of certain fetal organs [29]. The same organs are often the ones that are disproportionately large in SCNT fetuses. Although overexpression of IGF2 (with reference to house-keeping genes) was not observed in placental tissues from SCNT pregnancies, the increased placental mass means that overall, there must be more IGF2 produced and available to promote growth, assuming there is no difference in translational efficiency. The bioavailability of IGF2 is regulated through binding to the type 2 receptor (IGF2R) or to the IGF binding proteins (IGFBPs). The expression of IGF2R was shown to be altered in ovine large offspring syndrome [97]; however, this was not the case in bovine clones. Aberrant expression of the IGFBPs in bovine SCNT was reported [74], and even though the genes for these proteins are not imprinted, they regulate IGF2 bioavailability at a tissue-specific manner. The expression IGFBP2 was lower in the placental tissues from SCNT pregnancies [59]; thus, even if IGF2 production was not increased in clones, there was greater availability, as there was less IGFBPs to bind to it. The maternally expressed Phlda2 gene is included in a cluster of imprinted genes located on mouse chromosome 7, synthenic to a cluster on human chromosome 11p15.5 [73]. Phlda2 invalidated mice, with a lack of the maternal expression of Phlda2, are fertile but present enlarged placentae during pregnancy [35]. Conversely, the loss of imprint of Phlda2 leading to a bi allelic expression, causes fetal and placental growth retardation [80]. Similarly, an increased expression of PHLDA2 in human placenta is associated with low birth weights through putative reduction in size and function of the placenta [5]. In bovine, a reduced expression of Phlda2 is associated with pathological overgrowth of the placentomes from SCNT pregnancies and the level of expression of PHLDA2 is correlated negatively with total placentome weight in cloned placenta [40]. Altogether these data strongly support the idea that PHLDA2 acts as regulator of placental growth and may be involved in overgrowth observed after SCNT. Imprinted genes may regulate fetal growth by affecting the overall development and growth of the placenta or its functions, such as the supply of nutrients to the fetus via specific transporters and ion channels. Some of these transporter genes, such as the SLC22A genes are linked to IGF2R. It is not known if the expression of the SLC22A genes is affected in the SCNT placentas. Although a larger placenta may have a greater surface area over which to transfer nutrients, aberrations in vascular development may alter permeability and the increased mass, in addition, requires a greater share of the nutrients to maintain function. Placental mass is not always positively correlated with fetal weight in bovine s236
P.C .Cha havett ette-P e-Palmer almer, R.S.F. Lee ee, S. Camous amous, et al,. <strong>2011</strong>. The Placenta of Bovine Clones. fffffffffffffffffffffffffffffffffffffffffffffff ffffffff Acta Scientiae Veterinariae. 39(Suppl 1): s227 - s242. SCNT pregnancies, so a fine balance between supply and demand is required to maintain an appropriate rate of fetal growth. In female mammals, one of the two X- chromosomes is randomly inactivated in somatic cells in the body. Some SCNT embryos, aborted fetuses or dead newborn calves or viable offspring, however, showed aberrations in X-chromosome inactivation [96]. This has been attributed to faulty reprogramming of the donor nucleus. In the placenta, which normally show preferential paternal X-inactivation due to imprinting, random X- inactivation has been reported in SCNT placenta. It has been postulated that this aberrant X-inactivation may be deleterious to the development of SCNT fetuses or contribute to abnormal placental development. However, we did not see any gross differences in the severity of gestational pathologies, either in the placenta or fetus, whether male or female donor cells are used (Lee, et al., unpublished observations). There should not be any issues with X-inactivation when male donor cell lines are used, yet the outcome is no better compared with using female cell lines. Thus, aberrant X-inactivation is unlikely to be a major contributor to poor cloning outcomes. Finally, it must be noted that a high variability of global methylation has been reported in healthy adult clone cows [27]. Altogether, these studies highlight the importance to analyze the methylation status of specific loci in cloned embryos and offspring to understand the epigenetic disruption associated with the SCNT procedures. V. CONCLUSIONS In conclusion, SCNT affects many aspects of placental development in the bovine species, from the morphological structure to physiological function, gene expression and epigenetic marks. It is now well recognized that events occurring in the embryonic and fetal period may induce long term health effects in the offspring as developed through the study of the Developmental Origins of Health and Disease (DOHaD) [7,10,38]. Studying long term effects of cloning therefore must encompass the study of the effects of nuclear transfer per se as well as the secondary long term effects due to a perturbed placental function. REFERENCES N 1 Adams-Brendemuehl C. & Pipers F.S. 1987. Antepartum evaluations of the equine foetus. Journal of Reproduction and Fertility. 35 (Suppl): 565-573. 2 Agarwal A. & Allamaneni S. 2004. Role of free radicals in female reproductive diseses and assited reproduction. Reproductive BioMedicine Online. 9(3): 338-347. 3 Al-Gubory K.H., Garrel C., Delatouche L., Heyman Y. & Chavatte-Palmer P. 2010. Antioxidant adaptive responses of extraembryonic tissues from cloned and non-cloned bovine conceptuses to oxidative stress during early pregnancy. Reproduction. 140(1): 175-181. 4 Amor D.J. & Halliday J. 2008. A review of known imprinting syndromes and their association with assisted reproduction technologies. Human Reproduction. 23(12): 2826-2834. 5 Apostolidou S., Abu-Amero S., O’donoghue K., Frost J., Olafsdottir O., Chavele K.M., Whittaker J.C., Loughna P., Stanier P. & Moore G.E. 2007. Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight. Journal of Molecular Medicine. 85(4): 379-387. 6 Assis Neto A.C., Pereira F.T.V., Santos T.C., Ambrosio C.E., Leiser R. & Miglino M.A. 2010. Morpho-physical recording of bovine conceptus ( Bos indicus) and placenta from days 20 to 70 of pregnancy. Reproduction in Domestic Animals. 45(5): 760-772. 7 Barker D.J. 1995. The fetal and infant origins of disease. European Journal of Clinical Investigation. 25(7): 457-463. 8 Batchelder C.A., Bertolini M., Mason J.B., Moyer A.L., Hoffert K.A., Petkov S.G., Famula T.R., Angelos J., George L.W. & Anderson G.B. 2007. Perinatal physiology in cloned and normal calves: hematologic and biochemical profiles. Cloning and Stem Cells. 9(1): 83-96. 9 Batchelder C.A., Bertolini M., Mason J.B., Moyer A.L., Hoffert K.A., Petkov S.G., Famula T.R., Angelos J., George L.W. & Anderson G.B. 2007. Perinatal physiology in cloned and normal calves: physical and clinical characteristics. Cloning and Stem Cells. 9(1): 63-82. s237
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L.F. Nasser asser, L. Pen enteado e
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R.B. Lôbo, D. Nkr uman, D.A. Gross
Page 48 and 49:
R.B. Lôbo, D. Nkr uman, D.A. Gross
Page 51 and 52:
M.E.F .F. Oliv liveir eira. 2011. E
Page 53 and 54:
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A.L. Gusmão usmão. 2011. Estado d
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J. R. Figueir igueiredo edo, A.P.R.
Page 69 and 70:
E.L.A. Motta, M. Nichi & P.C. Ser e
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E.L.Gastal, M.O. Gastal, A. Wischra
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D.P .P.A.F .A.F. Braga & E. Bor org
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F.F .F. Bressan, F. Per erecin, eci
Page 108 and 109:
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Page 119 and 120:
C.E. Ambrósio mbrósio, C.V. Wenc
Page 121 and 122:
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Page 127 and 128:
J.C. Fer erreir eira, F.S. Ignácio
Page 129 and 130:
Page 131 and 132:
Page 133:
Page 136 and 137:
R.C. Uliani, L.A. Silv ilva, M.A. A
Page 138 and 139:
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F.S. Ignácio, J.C. Fer erreir eira
Page 142 and 143:
F.S. Ignácio, J.C. Fer erreir eira
Page 145 and 146:
L.A. Silva. 2011. Local Effect of t
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
M.M. Franc anco, A. Pellegr ellegri
Page 159 and 160:
M.M. Franc anco, A. Pellegr ellegri
Page 161 and 162:
B. Str troud & G.A. Bó. 2011. The
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
W.W .W. Tha hatcher cher. 2011. Tem
Page 171 and 172:
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O. Sandra. 2011. Deciphering early
Page 197 and 198:
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Page 203 and 204:
Page 205 and 206:
R.C. Cheb hebel. el. 2011. Use of A
Page 207 and 208: R.C. Cheb hebel. el. 2011. Use of A
Page 243: R.C. Cheb hebel. el. 2011. Use of A
Page 246 and 247: A.C.A. Net eto, A.R. Galdos aldos,
Page 248 and 249: A.C.A. Net eto, A.R. Galdos aldos,
Page 250 and 251: P.C .Cha havett ette-P e-Palmer alm
Page 266 and 267: E.H. Bir irgel Junior unior, F.V .V
Page 276 and 277: P. Humblot. 2011. Reproductive Tech
Page 286 and 287: J.A. Piedrahita. 2011. Application
Page 296 and 297: O.E. Smith, B.D. Murphy & L.C. Smit
Page 307 and 308: D. Salamone alamone, R. Bevacqua, F
Page 309 and 310:
D. Salamone alamone, R. Bevacqua, F
Page 311 and 312:
Page 313 and 314:
Page 315:
Page 318 and 319:
E.A. Maga & J.D. Mur urray. 2011. G
Page 320 and 321:
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Page 328 and 329:
C.G. Gutier utierrez, S. Fer errar
Page 330 and 331:
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Page 334 and 335:
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Page 338 and 339:
Page 340 and 341:
B. Gasparrini. 2011. Ovum pick-up a
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Acta Scientiae Veterinariae, 2011.
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