Ravelich S R, Shelling A N, Wells D N, Peterson A J, Lee R S F, Ramachandran A, Keelan J A
Liggins Institute, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Placenta. 2006 Feb-Mar;27(2-3):307-16. doi: 10.1016/j.placenta.2005.03.002. Epub 2005 Jun 13.
Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.
牛核移植妊娠的特点是胎盘异常发生率高,特别是胎盘小叶尺寸增大、滋养层细胞功能缺陷以及胎盘血管系统建立不足。胎盘生长和发育过程中的基因表达改变可能导致核移植妊娠中出现大胎盘小叶。胎盘合成多种细胞因子和生长因子,包括参与妊娠建立、维持和/或调节的转化生长因子-β(TGF-β)。所有形式的TGF-β及其受体都存在于牛胎盘小叶的胎儿-母体界面,据认为它们在调节胎盘的生长、分化和功能方面发挥重要作用。我们使用实时逆转录聚合酶链反应(RT-PCR),检测了人工授精(AI)和核移植(NT)来源的牛妊娠在妊娠第50、100和150天时胎盘小叶中TGF-β1、TGF-β2、TGF-β3以及受体TGF-βRI和TGF-βRII的表达。在所有检测的妊娠阶段,与AI对照组相比,NT胎盘小叶中TGF-β1、TGF-β2和TGF-β3的mRNA表达增加了2.0 - 2.8倍,而TGF-βRI和TGF-βRII的mRNA表达下降了1.7 - 2.0倍。这些发现表明,NT胎盘小叶可能对TGF-β的生长抑制作用具有抗性,并可能导致NT来源胎盘中观察到的胎盘增殖异常。或者,胎盘形成缺陷可能提供了一种机制,使得NT妊娠中TGF-β失调。