Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization.
Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization.
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分泌中期PIBF1/IL6/p-STAT3减少抑制人子宫内膜基质细胞增殖和蜕膜化
DOI：
10.1016/j.jare.2020.09.002
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发表时间：
2021-05
影响因子：
10.7
通讯作者：
Zhang A
中科院分区：
文献类型：
--
作者：
Zhou M;Xu H;Zhang D;Si C;Zhou X;Zhao H;Liu Q;Xu B;Zhang A
PIBF1在子宫内膜分泌中期达到高峰。RIF患者分泌期中期子宫内膜PIBF1表达降低。PIBF1通过IL6/p-STAT3信号调节HESC的增殖和蜕膜形成。RIF患者IL-6/p-STAT3、Ki-67、催乳素和IGFBP1水平较低。PIBF1的低表达可能是RIF患者子宫内膜容受性差的原因。复发性着床失败(RIF)是辅助生殖技术中的一个具有挑战性的问题，其主要原因是子宫内膜容受性不足，其发病机制尚不清楚。在这项研究中，我们首次研究了分泌中期PIBF1表达降低对RIF患者子宫内膜容受性的影响。基因芯片检测、逆转录定量聚合酶链式反应、蛋白质印迹和体外实验。结果表明，孕酮诱导阻断因子1(PIBF1)在对照组分泌中期子宫内膜中的表达最高，而在RIF患者中的表达明显降低。在Ishikawa和人子宫内膜间质细胞(HESCs)中，PIBF1基因敲除显著下调了细胞增殖和白介素6(IL6)和磷酸化信号转导和转录激活因子3(p-STAT3)水平，而不是人子宫内膜上皮细胞。此外，在体外蜕膜形成过程中，PIBF1基因敲除hESCs后，IL-6、p-STAT3、催乳素和胰岛素样生长因子结合蛋白-1(IGFBP1)的水平降低。PIBF1或IL6的过表达可显著恢复上述细胞变化。与我们对PIBF1的研究结果一致，RIF患者分泌中期子宫内膜中IL6、p-STAT3、Ki-67、催乳素和IGFBP1的水平显著低于对照组。综上所述，在分泌中期，PIBF1、IL6和p-STAT3的低表达抑制了HESC的增殖和蜕膜化，这对今后的研究和临床治疗策略具有重要的理论和临床意义。
PIBF1 levels peaked in the mid-secretory phase of endometrium. PIBF1 expression decreased in the mid-secretory endometrium of RIF patients. PIBF1 regulated HESC proliferation and decidualization via IL6/p-STAT3 signaling. The IL6/p-STAT3, Ki-67, prolactin, and IGFBP1 levels were lower in RIF patients. Low PIBF1 expression may account for poor endometrial receptivity in RIF patients. Recurrent implantation failure (RIF) is a challenging problem of assisted reproductive technology that arises mainly due to inadequate endometrial receptivity and its pathogenesis is still unclear. In this study, we conducted the first investigation of the effect of decreased PIBF1 expression in mid-secretory phase on endometrial receptivity in patients with RIF. Microarray assay, reverse transcriptase-quantitative polymerase chain reaction, western blot, and in-vitro experiments were conducted. The results showed that progesterone-induced blocking factor 1 (PIBF1) expression was highest in the mid-secretory endometrium in control subjects, but was significantly lower in RIF patients. In Ishikawa and human endometrial stromal cells (HESCs), rather than human endometrial epithelial cells, PIBF1 knockdown significantly downregulated cell proliferation and the levels of interleukin 6 (IL6) and phosphorylated signal transducer and activator of transcription-3 (p-STAT3). Besides, in HESCs, the levels of IL6, p-STAT3, prolactin and insulin-like growth factor binding-protein-1 (IGFBP1) decreased after PIBF1 knockdown during in-vitro decidualization. All these cellular changes could be notably restored by PIBF1 or IL6 overexpression. Consistent with our findings with PIBF1, the levels of IL6, p-STAT3, ki-67, prolactin, and IGFBP1 in the mid-secretory endometrium were notably lower in patients with RIF compared with controls. In summary, in the mid-secretory phase, decreased expression of PIBF1, IL6, and p-STAT3 inhibited HESC proliferation and decidualization, which is of theoretical and clinical importance for future research and clinical-treatment strategies.
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