Uterine Dnmt3a is not required for mouse embryo implantation.
Uterine Dnmt3a is not required for mouse embryo implantation.
复制标题
小鼠胚胎植入不需要子宫 Dnmt3a。
DOI：
10.2174/1566524020666200225115526
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
Rufei Gao
中科院分区：
文献类型：
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作者：
Na Li;Siyu Lu;Yubin Ding;Xuemei Chen;Junlin He;Xueqing Liu;Mengyue Chen;Juanjuan Zhang;Yan Su;Xue Zhang;Yingxiong Wang;Rufei Gao
背景
最近的研究表明，子宫内膜DNA甲基化是妊娠早期胚胎着床所必需的。DNMT3A是DNA甲基化的关键酶之一，在子宫内膜有规律的表达。
目标和方法
在这项研究中，我们使用孕酮受体-cre(Pgrcre)有条件地消融子宫DNMT3A，以确定DNMT3A在女性生殖中的生理作用。
结果
结果发现，妊娠早期卵巢功能无明显改变，Dnmt3aloxP/loxP Pgrcre/+(CKO)的胚胎着床位点数无明显变化。Western blotting和免疫组织化学结果显示雌激素受体(ERα)和粘蛋白1(MUc1)在子宫容受性的表达和定位上没有差异。虽然DNMT3A CKO雌鼠蜕膜组织中基质金属蛋白酶-2(MMP2)、基质金属蛋白酶-9(MMP9)和骨形态发生蛋白-2(BMP2)的表达略有下降，但对蜕膜化过程中小鼠子宫的大体形态无明显影响。在人工诱导蜕膜化模型中，DNMT3A CKO大鼠的视觉观察形态和子宫重量也无显著差异。最后，一项持续的育种研究表明，DNMT3A CKO雌性小鼠的生育力没有显著变化。
结论
总体而言，这些结果表明，尽管一些蜕膜标志物表达异常，但DNMT3A在子宫中的条件性敲除并不显著影响胚胎植入过程中的子宫内膜功能，胚胎可以正常植入子宫内膜。
BACKGROUND
Recent studies have demonstrated that endometrial DNA methylation is essential for embryo implantation during early pregnancy. Dnmt3a is one of the key enzymes for DNA methylation and could be expressed in the endometrium regularly at this stage.
OBJECTIVE AND METHODS
In this study, we conditionally ablated uterine Dnmt3a using progesterone receptor-cre (Pgrcre) to define the physiological roles of Dnmt3a in female reproduction.
RESULTS
We found that ovarian function was not apparently altered and the number of embryo implantation sites in Dnmt3aloxP/loxP Pgrcre/+ (cKO) was not significantly varied during early pregnancy. Western blotting and immunohistochemistry results showed no difference in expression or location of the estrogen receptor (ERα) and mucin 1 (Muc1), the marker of uterine receptivity. Although the expression of decidual markers, matrix metalloproteinase-2 (Mmp2), matrix metalloproteinase-9(Mmp9), and bone morphogenetic protein-2 (Bmp2), was slightly decreased in Dnmt3a cKO females, the gross morphology of mice uteri during decidualization was not significantly influenced. In the artificial induction of the decidualization model, there was also no remarkable difference in visual observed morphology or uterine weight in Dnmt3a cKO. Lastly, a continuous breeding study showed the fertility of Dnmt3a cKO female mice was not strikingly altered.
CONCLUSION
Overall, these results demonstrated that although some decidual markers are expressed abnormally, conditional knockout of Dnmt3a in the uterus did not significantly affect the endometrial function during embryo implantation; the embryo could implant into the endometrium normally.