Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation
Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation
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DOI：
10.1002/dvdy.1209
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发表时间：
2001-11-01
影响因子：
2.5
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Bagot, CN;Kliman, HJ;Taylor, HS
Hoxa 10是一个同源异型盒基因，在泌尿生殖道胚胎发生和成人生殖道中都有表达。母体Hoxa 10的表达是子宫内膜接受胚泡植入所必需的。Hoxa 10诱导子宫内膜发育到容受性状态的机制尚不清楚，因为Hoxa 10缺陷的子宫内膜在组织学上表现正常。我们改变了Hoxa 10在周期性成年雌性小鼠子宫中的表达，并在植入时通过透射电子显微镜检查子宫上皮形态的改变。胞饮足是子宫内膜上皮细胞表面的突起，在子宫内膜容受性时短暂发育。通过在着床前将Hoxa 10反义基因转染到周期性小鼠子宫中来阻断Hoxa 10表达，显著降低了胞饮足的数量。组成型表达Hoxa 10在子宫之前的正常时间pinopod形成导致pinopod数量增加。因此，Hoxa 10是松足类发育所必需的。Hox基因参与细胞增殖的调节和发育命运的决定。Hoxa 10通过调节子宫内膜间质细胞增殖和上皮细胞形态发生来证实子宫中的这种双重作用。综上所述，这些结果表明，母体Hoxa 10在pinopod发育中具有重要作用，Hoxa 10的这种功能可能有助于子宫内膜的容受性，以实现胚泡植入的目的。(C)2001 Wiley-Liss，Inc.
Hoxa10 is a homeobox gene that is expressed both during the embryogenesis of the genitourinary tract and in the adult reproductive tract. Maternal Hoxa10 expression is necessary for endometrial receptivity to blastocyst implantation. The mechanism by which Hoxa10 induces endometrial development to a state of receptivity is unknown as Hoxa10-deficient endometrium appears histologically normal. We altered the expression of Hoxa10 in the uterus of cycling adult female mice and examined the uterus at the time of implantation by transmission electron microscopy for alterations in epithelial morphology. Pinopods are projections on the surface of the uterine endometrial epithelial cells that develop transiently at the time of endometrial receptivity. Blocking Hoxa10 expression by transfection of Hoxa10 antisense into the cycling mouse uterus before implantation dramatically decreased pinopod number. Constitutively expressing Hoxa10 in the uterus just before the normal time of pinopod formation resulted in increased pinopod number. Therefore, Hoxa10 is necessary for pinopod development. Hox genes have been implicated in both the regulation of cellular proliferation and the determination of developmental fate. Hoxa10 exemplifies this dual role in the uterus by regulating both endometrial stromal cell proliferation and epithelial cell morphogenesis. Taken together, these results demonstrate that maternal Hoxa10 has an essential role in pinopod development and this function of Hoxa10 likely contributes to endometrial receptivity for the purpose of blastocyst implantation. (C) 2001 Wiley-Liss, Inc.