Implantation and Placental Development in Somatic Cell Clone Recipient Cows

Abstract

Successful somatic cloned animal production has been reported in various domesticated species, including cattle; however, it is associated with a high rate of pregnancy failure. The low cloning yield could possibly arise from either an abnormal and/or poorly developed placenta. In comparison to control cows, fewer placentomes were found in somatic cell nuclear recipient (NT) cows at day 60 of gestation, suggesting a retardation of fetal/placental growth in these animals. NT cows not only had fewer numbers of chorionic villi but also had poorly developed caruncles. Macroscopic examination revealed atypical development of the placentome in terms of shape and size. Histological disruption of chorionic villi and caruncular septum was found in NT cows. Of particular interest was that the expression of genes, as well as proteins in the placentome, was disparate between NT and artificially inseminated cows, especially placental lactogen (PL) and pregnancy-associated glycoprotein (PAG). In contrast, prolactin-related protein-1 (PRP-1) signals were comparable across cows, including NT cows carrying immotile fetuses. The expression of extracellular matrix degrading molecule, heparanase (HPA), in NT cows was divergent from that of control cows. Microarray data suggest that gene expression was disorientated in early stages of implantation in NT cows, but this was eliminated with progression of gestation. These findings strongly support a delay in trophoblast development during early stages of placentation in NT cows, and suggest that placental specific proteins, including PLs, PAGs, and HPA, are key indicators for the aberration of gestation and placental function in cows.

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.…”

“…In cattle at day 60 of gestation, there is disruption of Vet Pathol 45:6, 2008 chorionic villi and caruncular septa, being irregularly and sparsely arranged, associated with reduced procollagen type I and collagen type III fibers. 39 These changes are linked to increased expression of heparanase, an extracellular matrix-degrading enzyme, 55 in intercotyledonary areas. 39 In sheep at term with alive and healthy fetuses, the subtrophoblastic basement membrane and capillary basal lamina include increased thickness, lamellation, and deposition of collagen fibrils (Figs.…”

Excess estrogen sulfoconjugation as the possible cause for a poor sign of parturition in pregnant cows carrying somatic cell clone fetuses

“…Previously, several investigators suggested morphological and functional abnormalities of the placenta in clone fetuses in various gestational stages (Hill et al 2001, Hashizume et al 2002, Constant et al 2006; however, the role of the placenta in the final process of pregnancy, namely placental steroidgenesis and regulation of hormonal activity, is not fully understood. Therefore, analyses of placental events on the parturition process may help to overcome problems in the pre-partum period.…”

Placental function in development and disease

“…In cattle and sheep, the term placenta in clones is characterised by a reduced number of cotyledons, hydroallantois and hypertrophy of remaining placentomes (Hill et al 1999;De Sousa et al 2001). Interestingly, the maternal caruncles are also underdeveloped, implying that primary fetoplacental defects indirectly affect the mother also (Hashizume et al 2002). In more recent studies, examination of first trimester, cloned conceptuses showed that failure to establish cotyledons is common and likely accounts for the large number of conceptuses that fail during the first trimester (Hill et al 2000;Hashizume et al 2002).…”

“…Interestingly, the maternal caruncles are also underdeveloped, implying that primary fetoplacental defects indirectly affect the mother also (Hashizume et al 2002). In more recent studies, examination of first trimester, cloned conceptuses showed that failure to establish cotyledons is common and likely accounts for the large number of conceptuses that fail during the first trimester (Hill et al 2000;Hashizume et al 2002). Presumably only those conceptuses that have a threshold minimum number of cotyledons are able to survive and make it to term.…”