栄養代謝関連因子ならびにアポトーシス関連因子によるヒト絨毛細胞増殖能と機能発現の調節 : その絨毛病態への関わり(2 ヒト絨毛細胞の機能とその異常)

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Placental tissue contains a heterogeneous population of cells, including villous cytotrophoblasts(C-cells)and syncytiotrophoblast(S-cell), as well as extravillous trophoblast(EVT). It is evident that C-cells display highly proliferative properties, while S-cell displays various functions indispensable for the maintenance of pregnancy and fetal growth with little potential for proliferation. On the other hand, the development of the human fetus depends on the ability of EVT cells to invade the maternal uterine tissues in order to anochor placenta and fetus to the maternal endometrium and to gain access to the maternal circulation. We focused our attention on the effects of peroxisome proliferator, a nutrient cue and bcl-2, an apoptosis related oncogene on the trophoblast function. Peroxisome proliferators are thought to be mediated by the peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamilies. In addition to controlling genes involved in lipid metabolism, PPARs have also been implicated in the control of cell growth and differentiation. The reduction in JEG-3 cell growth caused by clofibric acid was associated with an increases in p53 mRNA. The p53 gene in JEG-3 cells is wild-type, raising the possibility that the clofibric acid-induced reduction in cell growth is a consequence of elevated p53 levels and consequently reduced cell cycle activity. Clofibric acid also had effects on JEG-3 cell endocrine activity. CGmRNAs were reduced by clofibric acid. In contrast, the mRNA level of cytochrome P450scc, a key steroidogenic enzyme, were not reduced. The mRNAs encoding PPARα, β were detected in human placentas, supporting the idea that clofibric acid works through the intermediary of PPARs. The expression of PPAR mRNAs in JEG-3 cells and the effects of PPAR stimulators on JEG-3 cell function suggest the possibility that PPAR modulators, such as fatty acids or their metabolites, may facilitate trophoblast differentiation. Bcl-2 protein is thought to be a cell survival gene which prevents apoptosis in a variety of cells. Bcl-2 protein was immunolocalized in the cytoplasm of S-cell, being least abundant in very early(4 to 5 weeks)placentas, less abundant in early placentas(6 to 12 weeks)and midterm placentas(16 to 20 weeks), and most abundant in term placentas(37-41 weeks). Western blot analysis of Bcl-2 protein in normal placenta confirmed an increase in Bcl-2 protein in normal placenta from 10 weeks to term. Moreover, apoptosis was noted in the nuclei of both C-cells and S-cell, being most abundant in very early placentas, less abundant in early placentas and midterm placentas, and least abundant in term placentas. Electron micrographs of very early placentas demonstrated ultrastructural changes consistent with apoptotic bodies. It is tempting to speculate that high levels of Bcl-2 protein in S-cell may prevent the death of terminally differentiated trophoblasts. EVT was classified into two morphological phenotypes as proposed by Kaufmann and Castellucci : proliferative phenotype EVT and invasive phenotype EVT. Apoptosis in EVT is more abundant in invasive phenotype EVT than in proliferative phenotype EVT. The increased occurrence of apoptosis in invasive phenotype EVT is consistent with the abundant expression of Fas and Fas-L and less expression of Bcl-2 protein in those cells. It seems likely that apoptosis in EVT during the invasion to decidua may be regulated by the interaction of these determinants. Thyroid hormone had been shown to have a physiological role in the maintenance of pregnancy due to its role as an enhancer of trophoblast endocrine function. However, to the authors knowledge, no study was done yet to evaluate the presence and effects of thyroid hormone(T3)on EVT cells. Thus, with the use of primary culture utilizing early placental EVT cells, we examined if T3 receptor exists in EVT cells and evaluate the effects of T3 on apoptosis of the cells. RT-PCR
社団法人日本産科婦人科学会の論文
2001-09-01

栄養代謝関連因子ならびにアポトーシス関連因子によるヒト絨毛細胞増殖能と機能発現の調節 : その絨毛病態への関わり(2 ヒト絨毛細胞の機能とその異常)

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