Placental abnormalities associated with post-natal mortality in sheep somatic cell clones

Review Paper: A Review of the Pathology of Abnormal Placentae of Somatic Cell Nuclear Transfer Clone Pregnancies in Cattle, Sheep, and Mice

“…101 In both ovine and bovine SCNT pregnancies, some investigators report that reduction in villous vascularization is accompanied by hypoplasia of trophoblastic epithelial cells, apoptosis and shedding of trophoblastic epithelial cells from foetal villi, 28 and/or reduced numbers of the trophoblastderived binucleate cells. 28,39,64,79 In these studies, caruncular and cotyledonary tissues were collected at 60 days of gestation from slaughtered cattle carrying SCNT motile and immotile embryos 39 and in sheep pregnancies at term with alive and healthy conceptus 28,64,79 or within 2 to 24 hours of fetal death. 28 Binucleate cells, which are homologues of the human extravillous trophoblast and rodent giant cells, normally migrate through the chorionic tight junctions to the uterine epithelium throughout gestation and produce several pregnancy-related proteins.…”

Nuclear reprogramming: what has been done and potential avenues for improvements

“…In mice [17] and cattle [18], a placental hypertrophy (placentomegaly) has been described, in contrast to findings in sheep [8]. In mice, the main histological abnormalities described are an increased number of glycogen cells and enlarged spongiotrophoblast cells [17].…”

“…Although abnormalities have been reported in cloned foetuses/offspring [14], often they result from placental fluid imbalances affecting kidney function and therefore general homeostasis [15]. The extra-embryonic tissues are in fact severely affected at all stages of foetal development [16], and even in full term clones [8]. So far, functional and morphological abnormalities of placenta have been studied only in mice, cow and sheep clones, while data from other cloned animals are missing.…”

“…In particular, an emerging insight is that development and function of extra-embryonic membranes is particularly affected by somatic cell nuclear transfer (SCNT) [4,5]. Such placentation dysfunction has dramatic effects on embryonic development and growth, leading to foetal losses in the most severe cases, and also the occurrence of stillbirth and postnatal mortality [6,7], particularly in sheep [8]. It is possible that the epigenetic mechanisms controlling gene expression in the extraembryonic tissue are less robust hat those acting on the foetus proper and therefore are more easily destabilized by invasive embryo technologies such as cloning.…”

Epigenetic Defects Related Reproductive Technologies: Large Offspring Syndrome (LOS)

“…Since then, oversized neonates and fetuses born after various manipulations of the embryo have been reported not only in calves, but also in sheep (Wilmut et al, 1997(Wilmut et al, , 2002 and mouse (Eggan et al, 2001;Fernández-Gonzalez et al, 2004;Wakayama et al, 1998). Up to 40% of SCNT-derived fullterm calves and lambs have LOS, which is characterized by large size at birth, enlarged umbilical cord, enlarged organs, hydrops of the fetus, lethargy, respiratory distress, muscle fiber composition, cerebellar dysplasia and skeletal and facial malformations (ChavattePalmer et al, 2002;Constant et al, 2006;Fletcher et al, 2007;Loi P et al, 2006;Maxfield et al, 1997;Schmidt et al, 1996;Walker et al, 1996;Young et al, 1998). Also, it is well known that in high frequency of LOS is also frequently observed in calves that developed from in vitro maturation (IVM) and IVF-derived embryos (Behboodi et al, 1995;Reichenbach et al, 1992;Bertolini et al, 2004).…”