WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse
WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse
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DOI：
10.1096/fj.10-175349
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
DeMayo, Francesco J.
中科院分区：
文献类型：
--
作者：
Franco, Heather L.;Dai, Daisy;DeMayo, Francesco J.
Wnt4是Wnt配体家族中的一员，对女性生殖道的发育至关重要。对妊娠期间成年子宫中WNT4表达的分析表明，WNT4可能在子宫内膜基质细胞的增殖、存活和分化中发挥作用，这是支持发育中的胚胎所必需的。为了研究Wnt4在成年子宫生理学中的作用，使用PRcre小鼠模型进行了Wnt4的条件消融。由于胚胎着床缺陷和随后子宫内膜基质细胞存活、分化和对孕激素信号反应的缺陷，切除Wnt4使雌性小鼠不能生育。除了基质细胞功能改变外，PRCRE/+Wnt4(f/f)(Wnt4(d/d))小鼠的子宫上皮分化也发生改变，特征是子宫腺数量减少，柱状腔上皮细胞下方出现p63阳性的基底细胞层。慢性雌激素治疗进一步加剧了改变的上皮细胞表型，导致WNT4(d/d)小鼠子宫上皮鳞状上皮化生。-Franco，H.L.，Dai，D.，Lee，K.Y.，Rubel，C.S.，Roop，D.，Boerom，D.，Jeong，J.-W.，Lydon，J.-P.，Bagchi，I.C.，Bagchi，M.K.，DeMayo，F.J.Wnt4是小鼠胚胎植入和蜕膜化过程中正常出生后子宫发育和孕激素信号的关键调节因子。FASE B J.25,1176-1187(2011)。Www.fasebj.org
WNT4, a member of the Wnt family of ligands, is critical for the development of the female reproductive tract. Analysis of Wnt4 expression in the adult uterus during pregnancy indicates that it may play a role in the regulation of endometrial stromal cell proliferation, survival, and differentiation, which is required to support the developing embryo. To investigate the role of Wnt4 in adult uterine physiology, conditional ablation of Wnt4 using the PRcre mouse model was accomplished. Ablation of Wnt4 rendered female mice subfertile due to a defect in embryo implantation and subsequent defects in endometrial stromal cell survival, differentiation, and responsiveness to progesterone signaling. In addition to altered stromal cell function, the uteri of PRcre/+ Wnt4(f/f) (Wnt4(d/d)) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands and the emergence of a p63-positive basal cell layer beneath the columnar luminal epithelial cells. The altered epithelial cell phenotype was further escalated by chronic estrogen treatment, which caused squamous cell metaplasia of the uterine epithelium in the Wnt4(d/d) mice. Thus, WNT4 is a critical regulator not only of proper postnatal uterine development, but also embryo implantation and decidualization.-Franco, H. L., Dai, D., Lee, K. Y., Rubel, C. S., Roop, D., Boerboom, D., Jeong, J.-W., Lydon, J.-P., Bagchi, I. C., Bagchi, M. K., DeMayo, F. J. WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 25, 1176-1187 (2011). www.fasebj.org