FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy

FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy
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FOXO3a 对于妊娠早期通过细胞凋亡的小鼠子宫内膜蜕膜化至关重要

DOI:
10.1002/jcp.27167
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发表时间:
2019-04-01
影响因子:
5.6
通讯作者:
Gao, Ru-Fei
Gao, Ru-Fei
中科院分区:
生物学2区
文献类型:
--
作者:
Long, Jing;Yang, Cheng-Shun;Gao, Ru-Fei

文献摘要

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胚胎着床是正常妊娠的必要条件,而蜕膜化过程是胚胎着床的关键。然而,早孕期蜕膜化的机制仍不清楚。叉头盒O3 a(FOXO 3a)是叉头盒家族中最重要的功能性转录因子,是凋亡相关基因的高度保守转录因子。在小鼠子宫中,发现FOXO 3a在妊娠早期的第1-7天有规律地表达。进一步探索后发现,在妊娠第5-7天,FOXO 3a在着床部位的表达水平明显高于着床间部位。在人工蜕膜化条件下,FOXO 3a在第一和第二蜕膜区高表达。蜕膜化后FOXO 3a在体内和体外的表达均显著增加。在原代间质细胞中,诱导蜕膜化后FOXO 3a的表达减少,从而减少了细胞凋亡。此外,当FOXO 3a-小干扰RNA转染到小鼠子宫中时,蜕膜化和凋亡相关因子的表达受损。因此,FOXO 3a可能在早孕蜕膜化过程中发挥重要作用,细胞凋亡可能是FOXO 3a调控蜕膜化的途径之一。
Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis‐related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1–7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5–7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a‐small interfering RNA was transfected into the uteri of mice, the expression of decidualization‐ and apoptosis‐related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a‐regulated decidualization.