Suppression of ERα Activity by COUP-TFII Is Essential for Successful Implantation and Decidualization
Suppression of ERα Activity by COUP-TFII Is Essential for Successful Implantation and Decidualization
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COUP-TFII抑制ERα活性对成功植入和蜕膜化至关重要
DOI：
10.1210/me.2009-0531
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发表时间：
2010-05-01
影响因子：
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通讯作者：
Tsai, Sophia Y.
中科院分区：
文献类型：
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作者：
Lee, Dong-Kee;Kurihara, Isao;Tsai, Sophia Y.
胚胎能力和子宫容受性之间的同步性对于成功植入至关重要。在子宫中消除鸡卵清蛋白上游启动子-转录因子II（COUP-TFII）的小鼠（PRCre/+; COUP-TFIIflox/flox）表现出着床缺陷和腔上皮中雌激素受体（ER）α活性增加，表明高ER α活性可能会破坏子宫容受性窗口。为了确定PRCre/+; COUP-TFIIflox/flox子宫中ER α活性的增加是否是植入缺陷的原因，我们评估了ER α活性的抑制是否可以挽救PRCre/+; COUP-TFIIflox/flox子宫植入缺陷。在受体期，将ICI 182，780（ICI）（一种纯ER α拮抗剂）给予PRCre/+、COUP-TFIIflox/flox突变体和COUP-TFIIflox/flox对照小鼠，并检查植入位点的数量。用油或ICI处理的COUP-TFIIflox/flox对照小鼠显示出正常数量的着床位点。正如预期的那样，在用油处理的PRCre/+; COUP-TFIIflox/flox突变小鼠中未观察到着床部位，与先前的观察结果一致。相比之下，ICI处理的PRCre/+; COUP-TFIIflox/flox突变小鼠的着床位点大大增加，尽管与对照小鼠相比数量减少。ICI治疗还能够恢复Wnt 4和骨形态发生蛋白2的表达，这对PRCre/+; COUP-TFIIflox/flox突变小鼠的子宫内膜蜕膜化很重要。为了证实胚胎附着和蜕膜化的拯救是ICI处理后ER α活性降低的结果，我们显示PRCre/+; COUP-TFIIflox/flox COUP-TFIIflox/flox突变小鼠中ER α靶基因的表达降低。由于COUP-TFII在我们的实验室中也被证明对妊娠期间的胎盘形成很重要，我们询问ICI治疗是否也可以挽救胎盘形成缺陷以允许这些小鼠的足月妊娠。我们发现，尽管给予ICI的COUP-TFIIflox/flox对照小鼠中出生了小鼠，但PRCre/+; COUP-TFIIflox/flox突变小鼠中没有出生幼崽，这表明ER α活性增加不是胎盘形成缺陷的原因。这些结果表明，在围着床期，COUP-TFII通过控制ER α活性来调节胚胎附着和蜕膜化。然而，COUP-TFII的表达仍然需要在着床后时期，以促进胎盘形成。（分子内分泌学24：930-940，2010）
Synchrony between embryo competency and uterine receptivity is essential for successful implantation. Mice with ablation of chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) in the uterus (PRCre/+; COUP-TFIIflox/flox) exhibit implantation defects and increased estrogen receptor (ER)alpha activity in the luminal epithelium, suggesting high ER alpha activity may disrupt the window of uterine receptivity. To determine whether increased ER alpha activity in the PRCre/+; COUP-TFIIflox/flox uterus is the cause of defective implantation, we assessed whether inhibition of ER alpha activity could rescue the PRCre/+; COUP-TFIIflox/flox uterine implantation defect. ICI 182,780 (ICI), a pure ER alpha antagonist, was administered to PRCre/+; COUP-TFIIflox/flox mutant and COUP-TFIIflox/flox control mice during the receptive period, and the number of implantation sites was examined. COUP-TFIIflox/flox control mice treated with oil or ICI showed the normal number of implantation sites. As expected, no implantation sites were observed in PRCre/+; COUP-TFIIflox/flox mutant mice treated with oil, consistent with previous observations. In contrast, implantation sites were greatly increased in ICI-treated PRCre/+; COUP-TFIIflox/flox mutant mice, albeit at a reduced number in comparison with the control mice. ICI treatment was also able to restore the expression of Wnt4 and bone morphogenetic protein 2, important for endometrial decidualization in the PRCre/+; COUP-TFIIflox/flox mutant mice. To confirm that the rescue of embryo attachment and decidualization is a consequence of a reduced ER alpha activity upon ICI treatment, we showed a reduction of the expression of ER alpha target genes in PRCre/+; COUP-TFIIflox/flox COUP-TFIIflox/flox mutant mice. Because COUP-TFII was also shown in our laboratory to be important for placentation during pregnancy, we asked whether ICI treatment could also rescue the placentation defect to allow full-term pregnancy in these mice. We found that whereas mice were born in COUP-TFIIflox/flox control mice given ICI, no pups were born in the PRCre/+; COUP-TFIIflox/flox mutant mice, suggesting that the increased ER alpha activity is not the reason for placentation defects. These results demonstrate that during the periimplantation period, COUP-TFII regulates embryo attachment and decidualization through controlling ER alpha activity. However, COUP-TFII expression is still required in the postimplantation period to facilitate placentation. (Molecular Endocrinology 24: 930-940, 2010)