Kim J J, Jaffe R C, Fazleabas A T
Department of Obstetrics and Gynecology, University of Illinois, Chicago 60612, USA.
Biol Reprod. 1998 Jul;59(1):160-8. doi: 10.1095/biolreprod59.1.160.
The process of decidualization involves the morphological and functional transformation of stromal fibroblasts to decidual cells. The objective of this study was to define appropriate in vitro culture conditions required for decidualization of baboon stromal cells. Parallel studies were also done with human endometrial stromal cells for comparative analysis. Human stromal cells produced prolactin and insulin-like growth factor-binding protein (IGFBP)-1 in response to hormones (estradiol-17beta [36 nM], medroxyprogesterone acetate [1 microM], and relaxin [100 ng/ml]), and production was enhanced in the presence of 0.1 mM dibutyryl cAMP (dbcAMP). By contrast, baboon cells did not produce any detectable levels of prolactin, even in the presence of hormones and dbcAMP. IGFBP-1 expression in baboon stromal cells was detectable by Day 6 of hormone and dbcAMP treatment and increased exponentially thereafter. In both human and baboon stromal cells, alpha smooth muscle actin (alphaSMA) expression, an early marker for decidualization in the baboon in vivo, was induced spontaneously under normal culture conditions. Furthermore, a decrease in alphaSMA expression was observed in cells producing high levels of IGFBP-1. Human cells produced significant levels of IGFBP-1 (p < or = 0.01) in response to short-term dbcAMP treatment (48 h) after 2 and 12 days of hormone treatment. However, baboon stromal cells required 17 days of hormonal treatment before cells became responsive to short-term dbcAMP treatment (p < or = 0.01). Finally, human endometrial stromal cells expressed the protein kinase A regulatory subunits RIalpha, RIbeta, RIIalpha, and RIIbeta whereas baboon stromal cells expressed RIalpha, RIIalpha, and RIIbeta. No difference in the mRNA expression of these isoforms was observed in decidualized or nondecidualized cells of either human or baboon endometrium. Our observations indicate that baboon stromal cells can be induced to decidualize in vitro and that this requires dbcAMP in addition to hormones. This is the first report demonstrating in vitro decidualization in a nonhuman primate.
蜕膜化过程涉及基质成纤维细胞向蜕膜细胞的形态和功能转变。本研究的目的是确定狒狒基质细胞蜕膜化所需的合适体外培养条件。还对人子宫内膜基质细胞进行了平行研究以作比较分析。人基质细胞在激素（雌二醇 - 17β[36 nM]、醋酸甲羟孕酮[1 μM]和松弛素[100 ng/ml]）作用下产生催乳素和胰岛素样生长因子结合蛋白（IGFBP）-1，并且在存在0.1 mM二丁酰环磷腺苷（dbcAMP）时产量增加。相比之下，即使存在激素和dbcAMP，狒狒细胞也未产生任何可检测水平的催乳素。在激素和dbcAMP处理的第6天可检测到狒狒基质细胞中IGFBP - 1的表达，此后呈指数增加。在人和狒狒基质细胞中，α平滑肌肌动蛋白（αSMA）表达，这是狒狒体内蜕膜化的早期标志物，在正常培养条件下自发诱导产生。此外，在产生高水平IGFBP - 1的细胞中观察到αSMA表达降低。在激素处理2天和12天后，短期dbcAMP处理（48小时）后人细胞产生显著水平的IGFBP - 1（p≤0.01）。然而，狒狒基质细胞在激素处理17天后细胞才对短期dbcAMP处理有反应（p≤0.01）。最后，人子宫内膜基质细胞表达蛋白激酶A调节亚基RIα、RIβ、RIIα和RIIβ，而狒狒基质细胞表达RIα、RIIα和RIIβ。在人或狒狒子宫内膜的蜕膜化或未蜕膜化细胞中，这些同工型的mRNA表达没有差异。我们的观察结果表明，狒狒基质细胞可在体外被诱导蜕膜化，并且这除了激素外还需要dbcAMP。这是第一份证明非人类灵长类动物体外蜕膜化的报告。
