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Type: Journal article
Title: Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise
Author: Fletcher, C.
Roberts, C.
Hartwich, K.
Walker, S.
McMillen, I.
Citation: Reproduction, 2007; 133(1):243-255
Publisher: Bio Scientifica Ltd
Issue Date: 2007
ISSN: 1470-1626
Statement of
C J Fletcher, C T Roberts, K M Hartwich, S K Walker and I C McMillen
Abstract: The efficiency of cloning by somatic cell nuclear transfer (SCNT) is poor in livestock with ~5% of transferred cloned embryos developing to term. SCNT is associated with gross placental structural abnormalities. We aimed to identify defects in placental histology and gene expression in failing ovine cloned pregnancies to better understand why so many clones generated by SCNT die in utero. Placentomes from SCNT pregnancies (n = 9) and age matched, naturally mated controls (n = 20) were collected at two gestational age ranges (105–134 days and 135–154 days; term = 147 days). There was no effect of cloning on total placental weight. However, cloning reduced the number of placentomes at both gestational ages (105–134 days: control 55.0 ± 4.2, clone 44.7 ± 8.0 and 135–154 days: control 72.2 ± 5.1, clone 36.6 ± 5.1; P < 0.001) and increased the mean individual placentome weight (105–134 days: control 10.6 ± 1.3 g, clone 18.6 ± 2.8 g and 135–154 days: control 6.6 ± 0.6 g, clone 7.0 ± 2.0 g; P < 0.02). Placentomes from cloned pregnancies had a significant volume of shed trophoblast and fetal villous hemorrhage, absent in controls, at both gestational age ranges (P < 0.001) that was shown to be apoptotic by activated caspase-3 immunoreactivity. Consequently, the volume of intact trophoblast was reduced and the arithmetic mean barrier thickness of trophoblast through which exchange occurs was altered (P < 0.001) at both gestational age ranges in clones. In addition, cloning reduced placental expression of key genes in placental differentiation and function. Thus, cloning by SCNT results in both gross and microscopic placental abnormalities. We speculate that trophoblast apoptosis, shedding, and hemorrhage may be causal in fetal death in ovine clones.
Keywords: Trophoblasts
Sheep, Domestic
Fetal Death
Blood Glucose
Insulin-Like Growth Factor I
Receptor, IGF Type 2
RNA, Messenger
Organ Size
Embryo Transfer
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gestational Age
Nuclear Transfer Techniques
Embryo, Mammalian
Description: Copyright © 2007 Society for Reproduction and Fertility
DOI: 10.1530/rep.1.01203
Published version:
Appears in Collections:Aurora harvest 6
Obstetrics and Gynaecology publications

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