Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium.
Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium.
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DOI：
10.1210/endo.137.7.8770938
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发表时间：
1996-07
期刊：
影响因子：
4.8
通讯作者：
K. Akcali;Sohaib A. Khan;Bruce C. Moulton
中科院分区：
文献类型：
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作者：
K. Akcali;Sohaib A. Khan;Bruce C. Moulton
在妊娠早期，子宫内膜对植入胚泡的反应伴随着蜕膜的广泛生长和分化。子宫内膜间质细胞的这种转化始于子宫的反子宫内膜侧，形成一个初级蜕膜区，然后在反子宫内膜扩张形成次级蜕膜区，最终转化为子宫系膜区的间质细胞。在妊娠期间，两个蜕膜带都会因细胞凋亡而退化，留下子宫系膜区域的蜕膜细胞形成基底层蜕膜和成熟的胎盘。控制胚泡着床和蜕膜形成过程中细胞死亡的分子机制尚不清楚。我们验证了孕激素和雌激素对子宫内膜分化和最终细胞凋亡的调控涉及bcl2基因家族表达的假说。去卵巢大鼠在宫内刺激开始蜕膜形成之前，先用雌二醇预处理，再用孕激素(醋酸甲羟孕酮3.5 mg)和雌二醇(200 Ng)处理。在激素处理和蜕膜化后，Northern印迹分析检测到Bax信使RNA的两个转录本1.0和1.5kb的表达，仅诱导出1.0kb的转录本。同样的处理后，细胞凋亡抑制因子bcl2的表达减少。原位分析显示，在激素治疗和蜕膜化后，Bax的细胞类型特异性表达增加。宫内刺激后24小时，子宫腔上皮细胞和腺体上皮细胞首先出现这种增加，然后在瘤周间质中逐渐表达，最终在整个间质中逐渐表达。激素治疗和蜕膜化后bcl2表达下降。Bax免疫组织化学研究显示，Bax蛋白的表达伴随着间质的蜕膜化。Bcl2蛋白仅见于子宫腔上皮和腺上皮，其表达水平随着蜕膜化程度的加深而降低。这些数据表明，在基质细胞分化过程中，bax和bcl2表达之间的平衡发生了变化。Bax的表达增加先于核小体DNA断裂和最终的细胞凋亡，这在胎盘发育中起着重要的作用。
During early pregnancy, the uterine endometrium responds to an implanting blastocyst with the extensive growth and differentiation of decidualization. This transformation of endometrial stromal cells begins in the antimesometrial side of the uterus to form a primary decidual zone, expands to form a secondary zone in the antimesometrium, and eventually transforms stromal cells in the mesometrial region. During pregnancy, both decidual zones regress by apoptosis, leaving decidual cells in the mesometrial region to form decidua basalis and the mature placenta. Molecular mechanisms controlling cell death during blastocyst implantation and decidualization are unknown. We examined the hypothesis that progesterone and estrogen control of endometrial differentiation and eventual apoptosis involves control of bcl-2 gene family expression. Ovariectomized rats were primed with estradiol and treated with progestin (medroxyprogesterone acetate, 3.5 mg) and estradiol (200 ng) before an intrauterine stimulus to initiate decidualization. Expression of the two bax messenger RNA transcripts, 1.0 and 1.5 kilobases, was examined by Northern blot analysis after hormone treatment and decidualization, and only the 1.0-kilobase transcript was induced. After the same treatments, the expression of bcl-2, a suppressor of apoptosis, decreased. In situ analysis revealed a cell type-specific increase in bax expression after the hormonal treatment and decidualization. This increase was first seen in luminal and glandular epithelial cells and then in the periluminal stroma 24 h after intrauterine stimulation, with eventual progressive expression throughout the stroma. Expression of bcl-2 decreased after hormone treatment and decidualization. Immunohistochemical studies of Bax showed that expression of Bax protein accompanied decidualization of the stroma. Bcl-2 protein was only seen in the luminal and glandular epithelia, and its level decreased as decidualization progressed. These data indicate that the balance between bax and bcl-2 expression is altered during stromal cell differentiation. Increased expression of bax precedes nucleosomal DNA fragmentation and eventual apoptosis, which plays a significant role in placental development.