Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise
Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise
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DOI：
10.1530/rep.1.01203
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发表时间：
2007-01-01
期刊：
影响因子：
3.8
通讯作者：
McMillen, I. C.
中科院分区：
文献类型：
--
作者：
Fletcher, C. J.;Roberts, C. T.;McMillen, I. C.
通过体细胞核移植（SCNT）克隆家畜的效率很低，大约只有5%的移植克隆胚胎发育到足月。SCNT与总体胎盘结构异常相关。我们的目的是确定胎盘组织学和基因表达的缺陷，在失败的绵羊克隆妊娠，以更好地理解为什么这么多的克隆产生的SCNT在子宫内死亡。在两个胎龄范围（1105-134天和135-154天;足月= 147天）收集SCNT妊娠（n= 9）和年龄匹配的自然交配对照（n= 20）的胎盘。克隆对胎盘总重量无影响。然而，克隆减少了两个胎龄的胎盘数量（105-134天：对照组55.0 +/- 4.2，克隆组44.7 +/- 8.0和135-154天：对照组72.2 +/- 5.1，克隆组36.6 +/- 5.1; P < 0.001），并增加平均个体胎盘重量（1105-134天：对照10.6 +/-1.3g，克隆18.6 +/-2.8g，135-154天：对照6.6 +/-0.6g，克隆7.0 +/-2.0g; P < 0.02）。在两个胎龄范围内，克隆妊娠的胎盘组织都有大量脱落的滋养层细胞和胎儿绒毛出血，而对照组则没有（P < 0.001），活化的caspase-3免疫反应性表明胎盘组织是凋亡的。因此，在两个胎龄范围内，完整滋养层的体积减少，滋养层屏障的算术平均厚度发生改变（P < 0.001）。此外，克隆降低了胎盘分化和功能中关键基因的胎盘表达。因此，通过SCNT进行克隆会导致肉眼和显微镜下的胎盘异常。我们推测，滋养层细胞凋亡，脱落，出血可能是绵羊克隆胎儿死亡的原因。
The efficiency of cloning by somatic cell nuclear transfer (SCNT) is poor in livestock with similar to 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 (1105-134 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 (1105-134 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.