Department of Animal Science, Texas A&M University, College Station, TX, USA.
Biol Reprod. 2011 Aug;85(2):386-96. doi: 10.1095/biolreprod.111.091769. Epub 2011 Apr 20.
The success of postnatal uterine morphogenesis dictates, in part, the embryotrophic potential and functional capacity of the adult uterus. The definitive role of Wnt7a in postnatal uterine development and adult function requires a conditional knockout, because global deletion disrupts müllerian duct patterning, specification, and cell fate in the fetus. The Wnt7a-null uterus appears to be posteriorized because of developmental defects in the embryo, as evidenced by the stratified luminal epithelium that is normally found in the vagina and the presence of short and uncoiled oviducts. To understand the biological role of WNT7A after birth and allow tissue-selective deletion of Wnt7a, we generated loxP-flanked exon 2 mice and conditionally deleted Wnt7a after birth in the uterus by crossing them with Pgr(Cre) mice. Morphological examination revealed no obvious differences in the vagina, cervix, oviduct, or ovary. The uteri of Wnt7a mutant mice contained no endometrial glands, whereas all other uterine cell types appeared to be normal. Postnatal differentiation of endometrial glands was observed in control mice, but not in mutant mice, between Postnatal Days 3 and 12. Expression of morphoregulatory genes, particularly Foxa2, Hoxa10, Hoxa11, Msx1, and Wnt16, was disrupted in the Wnt7a mutant uteri. Conditional Wnt7a mutant mice were not fertile. Although embryos were present in uteri of mutant mice on Day 3.5 of pregnancy, blastocyst implantation was not observed on Day 5.5. Furthermore, expression of several genes (Foxa2, Lif, Msx1, and Wnt16) was reduced or absent in adult Wnt7a-deleted uteri on Day 3.5 postmating. These results indicate that WNT7A plays a critical role in postnatal uterine gland morphogenesis and function, which are important for blastocyst implantation and fertility in the adult uterus.
产后子宫形态发生的成功在一定程度上决定了成年子宫的胚胎营养潜力和功能能力。Wnt7a 在产后子宫发育和成年功能中的明确作用需要条件性敲除，因为全局缺失会破坏胎儿中缪勒管的模式形成、特化和细胞命运。Wnt7a 缺失的子宫似乎向后移位，这是由于胚胎发育缺陷，表现为正常存在于阴道的分层腔上皮和短而未卷曲的输卵管。为了了解 WNT7A 出生后的生物学作用并允许组织选择性删除 Wnt7a，我们生成了loxP 侧翼的外显子 2 小鼠，并通过与 Pgr(Cre) 小鼠杂交在子宫中出生后条件性删除 Wnt7a。形态学检查显示阴道、宫颈、输卵管或卵巢没有明显差异。Wnt7a 突变小鼠的子宫没有子宫内膜腺，而所有其他子宫细胞类型似乎正常。在对照小鼠中，在产后第 3 天到第 12 天之间观察到子宫内膜腺的产后分化，但在突变小鼠中没有观察到。形态调节基因的表达，特别是 Foxa2、Hoxa10、Hoxa11、Msx1 和 Wnt16，在 Wnt7a 突变子宫中受到干扰。条件性 Wnt7a 突变小鼠不能生育。尽管在妊娠第 3.5 天，突变小鼠的子宫中有胚胎，但在第 5.5 天没有观察到胚泡着床。此外，在产后第 3.5 天交配后的成年 Wnt7a 缺失子宫中，一些基因（Foxa2、Lif、Msx1 和 Wnt16）的表达减少或缺失。这些结果表明，WNT7A 在产后子宫腺形态发生和功能中发挥关键作用，这对于成年子宫中的胚泡着床和生育能力很重要。
