Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause
Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause
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DOI：
10.1210/en.2010-0955
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Murphy, Bruce D.
中科院分区：
文献类型：
--
作者：
Lefevre, Pavine L. C.;Palin, Marie-France;Murphy, Bruce D.
胚胎滞育是胚胎着床前发育可逆性停止的一种鲜为人知的现象。许多食肉动物，如水貂，每次怀孕都有滞育的特征。胚胎再激活是由子宫控制的，其机制尚不明确。由于多胺是细胞增殖和生长的重要调节因子，因此假设它们会触发胚胎再激活。为了验证这一点，交配的雌性水貂在重新激活的前5天使用α -二氟甲基鸟氨酸（一种鸟氨酸脱羧酶1的抑制剂，多胺生物合成的限速酶）或生理盐水作为对照。这种处理诱导多胺剥夺，导致胚胎细胞增殖再次停滞。经α -二氟甲基鸟氨酸处理的水貂滋养细胞细胞系同样表现出细胞增殖停滞、形态改变和鸟氨酸脱羧酶1蛋白的细胞内易位。胚胎发育的停滞使着床延迟了一段与治疗时间一致的时间。随后成功植入并分娩。我们得出结论，多胺剥夺带来了胚胎发育的可逆再停滞，使水貂胚胎回到滞育状态，并导致胚胎着床的第二次延迟。该结果首次证明了在专性滞育中胚胎再激活所必需的一个因素。（内分泌学152:1627-1639,2011）
Embryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation and growth, it was hypothesized that they trigger embryo reactivation. To test this, mated mink females were treated with alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, or saline as a control during the first 5 d of reactivation. This treatment induced polyamine deprivation with the consequence of rearrest in embryo cell proliferation. A mink trophoblast cell line in vitro subjected to alpha-difluoromethylornithine treatment likewise displayed an arrest in cell proliferation, morphological changes, and intracellular translocation of ornithine decarboxylase 1 protein. The arrest in embryo development deferred implantation for a period consistent with the length of treatment. Successful implantation and parturition ensued. We conclude that polyamine deprivation brought about a reversible rearrest of embryo development, which returned the mink embryo to diapause and induced a second delay in embryo implantation. The results are the first demonstration of a factor essential to reactivation of embryos in obligate diapause. (Endocrinology 152: 1627-1639, 2011)