Evidence that absence of endometrial gland secretions in uterine gland knockout ewes compromises conceptus survival and elongation
Evidence that absence of endometrial gland secretions in uterine gland knockout ewes compromises conceptus survival and elongation
复制标题
DOI：
10.1530/rep.0.1240289
复制
发表时间：
2002-08-01
期刊：
影响因子：
3.8
通讯作者：
Spencer, TE
中科院分区：
文献类型：
--
作者：
Gray, CA;Burghardt, RC;Spencer, TE
子宫内膜腺是孕体着床和生长所必需的。在绵羊子宫腺敲除（UGKO）模型中，囊胚正常孵化，但无法存活或伸长。 UGKO 母羊的这种围着床缺陷可能是由于缺乏子宫内膜腺体，或者是由于缺乏某些上皮粘附分子或子宫内膜无法对来自孕体的信号做出反应。进行了两项研究来检验这些假设。在研究一中，正常 (n = 8) 和 UGKO (n = 12) 母羊在发情时（第 0 天）与完整的公羊交配，并在发情后 14 天冲洗其子宫。正常母羊（n = 4）也在发情后14天进行冲洗。正常繁殖母羊的子宫冲洗含有丝状受孕体（n = 8 只中的 7 只），而 UGKO 母羊的子宫冲洗物不含受孕体（n = 12 只中的 5 只）、生长迟缓的管状受孕体（12 只中 n = 6 只）或破碎的丝状受孕体（12 只中 n = 1 只）。在所有组中，粘蛋白1和整合素α(v)、α(5)、β(3)和β(5)的表达均位于子宫内膜腔上皮的顶端表面，正常和UGKO母羊之间没有可检测到的差异。怀孕母羊（但不是周期性或 UGKO 母羊）的子宫潮红含有丰富的免疫反应性干扰素 tau 和细胞粘附蛋白、骨桥蛋白和糖基化依赖性细胞粘附分子之一。在研究二中，UGKO母羊在发情后5天安装子宫导管，在发情后11至15天输注重组羊干扰素T或对照蛋白，并在发情后16天接受子宫切除术。注射干扰素 tau 的 UGKO 母羊子宫内膜中几种干扰素 tau 刺激基因（ISG17、STAT1、STAT2 和 IRF-1）的表达增加。这些结果支持这样的假设：UGKO母羊的概念伸长和存活的缺陷是由于子宫内膜腺体及其分泌物的缺乏，而不是由于子宫内膜腔上皮上抗粘附或粘附分子表达的改变或子宫内膜对概念妊娠识别信号的反应性的改变。
Endometrial glands are necessary for conceptus implantation and growth. In the ovine uterine gland knockout (UGKO) model, blastocysts hatch normally but fail to survive or elongate. This peri-implantation defect in UGKO ewes may be due to the absence of endometrial glands or, alternatively, to the lack of certain epithelial adhesion molecules or the inability of the endometrium to respond to signals from the conceptus. Two studies were performed to examine these hypotheses. In study one, normal (n = 8) and UGKO (n = 12) ewes were mated at oestrus (day 0) with intact rams and their uteri were flushed 14 days after oestrus. Normal ewes (n = 4) were also flushed on 14 days after oestrus. Uterine flushes from bred normal ewes contained filamentous conceptuses (n = 7 of 8), whereas those from UGKO ewes contained no conceptus (n = 5 of 12), a growth-retarded, tubular conceptus (n = 6 of 12), or a fragmented, filamentous conceptus (n = 1 of 12). In all groups, expression of mucin 1 and integrin alpha(v), alpha(5), beta(3) and beta(5) was localized at the apical surface of the endometrial luminal epithelium with no detectable differences between normal and UGKO ewes. Uterine flushes from pregnant ewes, but not cyclic or UGKO ewes, contained abundant immunoreactive interferon tau and the cell adhesion proteins, osteopontin and glycosylation-dependent cell adhesion molecule one. In study two, UGKO ewes were fitted with uterine catheters 5 days after oestrus, infused with recombinant ovine interferon T or control proteins from 11 to 15 days after oestrus, and underwent hysterectomy 16 days after oestrus. Expression of several interferon tau-stimulated genes (ISG17, STAT1, STAT2 and IRF-1) was increased in the endometrium from interferon tau-infused UGKO ewes. These results support the hypothesis that the defects in conceptus elongation and survival in UGKO ewes are due to the absence of endometrial glands and their secretions rather than to alterations in expression of anti-adhesive or adhesive molecules on the endometrial luminal epithelium or to the responsiveness of the endometrium to the conceptus pregnancy recognition signal.