Center for Reproductive Biology, Department of Animal Sciences, Washington State University, Pullman, Washington 99164-6310, USA.
Biol Reprod. 2013 Apr 11;88(4):93. doi: 10.1095/biolreprod.113.107631. Print 2013 Apr.
Uterine glands and their secretions are hypothesized to be essential for blastocyst implantation and decidualization in the uterus of rodents and humans. One factor solely expressed by uterine glands in mice is leukemia inhibitory factor (LIF), and Lif null mice are infertile because of defective blastocyst attachment to the uterine luminal epithelium (LE). Progesterone treatment of neonatal mice permanently ablates differentiation of uterine glands, resulting in an aglandular uterus in the adult. Progesterone-induced uterine gland knockout (PUGKO) mice were used to investigate the biological role of uterine glands in blastocyst implantation and stromal cell decidualization. As compared to controls, PUGKO mice cycled normally but were infertile. Histological assessment of PUGKO uteri on Days 5.5 and 8.5 postmating found a hatched blastocyst apposed to an intact LE without evidence of implantation or stromal cell decidualization. Expression of several implantation-related factors, including Lif and PTGS2, were altered in the PUGKO uterus, whereas expression of steroid hormone receptors and their regulated genes was not different. Artificial decidualization was observed in the uteri of control but not PUGKO mice. Further, intrauterine administration of LIF failed to promote artificial decidualization in the uterus of PUGKO mice. Thus, uterine glands and their secretions have important biological roles in blastocyst implantation and stromal cell decidualization in the uterus.
子宫腺体及其分泌物被认为对啮齿动物和人类的胚胎着床和蜕膜化至关重要。在小鼠中,唯一由子宫腺体表达的一个因子是白血病抑制因子(LIF),而 Lif 基因敲除小鼠由于胚胎附着到子宫腔上皮(LE)的缺陷而不育。新生小鼠的孕激素处理可永久性地破坏子宫腺体的分化,导致成年后出现无腺子宫。利用孕激素诱导的子宫腺体敲除(PUGKO)小鼠来研究子宫腺体在胚胎着床和基质细胞蜕膜化中的生物学作用。与对照组相比,PUGKO 小鼠正常发情,但不育。交配后第 5.5 天和第 8.5 天的 PUGKO 子宫组织学评估发现,孵出的胚胎紧贴完整的 LE,但没有着床或基质细胞蜕膜化的证据。在 PUGKO 子宫中,一些与着床相关的因子(包括 Lif 和 PTGS2)的表达发生改变,而甾体激素受体及其调控基因的表达没有差异。在对照组小鼠的子宫中观察到人工蜕膜化,但在 PUGKO 小鼠的子宫中没有。此外,在 PUGKO 小鼠的子宫内给予 LIF 并不能促进人工蜕膜化。因此,子宫腺体及其分泌物在胚胎着床和基质细胞蜕膜化中具有重要的生物学作用。