Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice
Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice
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DOI：
10.1095/biolreprod56.5.1097
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发表时间：
1997-05-01
影响因子：
3.6
通讯作者：
Markoff, E
中科院分区：
文献类型：
--
作者：
Gendron, RL;Paradis, H;Markoff, E
在这里，我们详细描述了HOXA-11在野生型小鼠子宫中的表达以及导致HOXA-11基因缺失雌性小鼠母体生殖失败的缺陷。Hoxa-11基因在动情后期子宫基质细胞中的表达水平达到高峰。HOXA-11转录本在妊娠第2天开始在子宫上皮下的基质细胞中被诱导，并在妊娠第6天至第8天出现在次级蜕膜区。在妊娠早期，Hoxa-11缺失子宫与野生型相比，间质、蜕膜和腺细胞发育不足，根据组织学和蜕膜细胞标志物表位阶段特异性胚胎抗原-3(SSEA-3)的免疫组织化学定位。在诱导假孕后，激素诱导的子宫间质和腺体细胞的增殖以及油诱导的间质蜕膜形成在突变子宫中都是缺乏的。此外，免疫组织化学和Western blotting均显示，HOXA-11基因缺陷的子宫腺白血病抑制因子(LIF)在妊娠4.5天的正常子宫中缺失。在双侧卵巢切除、激素刺激的Hoxa-11突变体的子宫中也没有观察到LIF爆发。这些结果表明，HOXA-11基因是正常的子宫基质细胞和孕期腺体分化所必需的，类固醇诱导的腺体LIF爆裂启动胚胎着床也是如此。
Here we describe in detail both the expression of Hoxa-11 in the wild-type mouse uterus and the defects resulting in maternal reproductive failure of Hoxa-11 null female mice. The Hoxa-11 gene is expressed at peak levels in uterine stromal cells during metestrus. Hoxa-11 transcripts were induced beginning on Day 2 of gestation in the stromal cells underlying the uterine epithelium and appeared in the secondary decidual zone between Days 6 and 8 of gestation. At early gestational stages, stromal, decidual, and glandular cell development were deficient in Hoxa-11 null uteri in comparison to wild-type as assessed by histology and immunohistochemical localization of the decidual cell marker epitope, stage-specific embryonic antigen-3 (SSEA-3). Both steroid-induced uterine stromal and glandular cell proliferation as well as oil-induced stromal decidualization after induction of pseudopregnancy were deficient in mutant uteri. Moreover, both Western blotting and immunohistochemistry demonstrated that the burst of glandular leukemia inhibitory factor (LIF) found in normal pregnant uteri at Day 4.5 of gestation was absent in Hoxa-11-deficient uteri. The LIF burst was also not observed in the uteri of bilaterally ovariectomized, hormonally stimulated Hoxa-11 mutants. These results demonstrate that the Hoxa-11 gene is required for normal uterine stromal cell and glandular differentiation during pregnancy, as is the presence of the steroid-induced glandular LIF burst initiating embryo implantation.