WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland Development
WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland Development
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DOI：
10.1095/biolreprod.110.088161
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
MacLean, James A., II
中科院分区：
文献类型：
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作者：
Hayashi, Kanako;Yoshioka, Shin;MacLean, James A., II
WNT 是控制重要发育过程的分泌蛋白，例如胚胎模式、细胞生长、迁移和分化。在小鼠中，Wnt 基因家族的三个成员（Wnt4、Wnt5a 和 Wnt7a）已在雌性生殖道中进行了广泛研究。本研究确定了出生后一天和暴露于己烯雌酚 (DES) 对小鼠子宫中 Wnt 和 Fzd 基因表达的影响，以及 Wnt11 在出生后小鼠子宫发育和功能中的生物学作用。通过原位杂交在新生小鼠子宫中检测到 Wnt4、Wnt5a、Wnt7a、Wnt7b、Wnt11、Wnt16、Fzd6 和 Fzd10。原位杂交分析显示，Wnt4、Wnt5a 和 Wnt16 位于子宫内膜基质中，而 Wnt7a、Wnt7b、Wnt11、Fzd6 和 Fzd10 位于新生小鼠的子宫上皮中。小鼠在关键发育时期暴露于雌激素或雌激素受体激动剂会抑制子宫内膜腺发生。在本研究中，DES 诱导的子宫内膜腺体发育破坏与 Wnt4、Wnt5a、Wnt7a、Wnt11、Wnt16 和 Fzd10 的减少或抑制有关。 Wnt11（一种上皮表达的 DES 调节基因）在新生儿子宫中的消融不会影响子宫内膜腺发生或其他 Wnt 基因的表达。有趣的是，Wnt11缺失的子宫在出生后第10天有更多的子宫内膜腺体。虽然CTNNB1的表达不受Wnt11消融的影响，但Vangl2在Wnt11(d/d)小鼠的子宫中受到抑制。这些结果支持了以下观点：许多不同的 Wnt 基因是子宫形态发生的潜在调节因子。然而，Wnt11对子宫发育没有直接影响。
The WNTs are secreted proteins that control essential developmental processes, such as embryonic patterning, cell growth, migration, and differentiation. In mice, three members of the Wnt gene family (Wnt4, Wnt5a, and Wnt7a) have been studied extensively in the female reproductive tract. The present study determined effects of postnatal day and exposure to diethylstilbestrol (DES) on Wnt and Fzd gene expression in the mouse uterus as well as the biological role of Wnt11 in postnatal mouse uterine development and function. Wnt4, Wnt5a, Wnt7a, Wnt7b, Wnt11, Wnt16, Fzd6, and Fzd10 were detected by in situ hybridization in the neonatal mouse uterus. In situ hybridization analyses revealed that Wnt4, Wnt5a, and Wnt16 were localized in the endometrial stroma, whereas Wnt7a, Wnt7b, Wnt11, Fzd6, and Fzd10 were in the uterine epithelia of neonatal mice. Exposure of mice to estrogen or estrogen receptor agonists during critical development periods inhibits endometrial adenogenesis. In the present study, DES-induced disruption of endometrial gland development was associated with reduction or suppression of Wnt4, Wnt5a, Wnt7a, Wnt11, Wnt16, and Fzd10. Ablation of Wnt11, an epithelial-expressed, DES-regulated gene, in the neonatal uterus did not affect endometrial adenogenesis or expression of other Wnt genes. Interestingly, Wnt11-deleted uteri had more endometrial glands on Postnatal Day 10. Although CTNNB1 expression was not affected by ablation of Wnt11, Vangl2 was inhibited in the uteri of Wnt11(d/d) mice. These results support the idea that a number of different Wnt genes are potential regulators for uterine morphogenesis; however, Wnt11 does not have a direct effect on uterine development.