Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation.
Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation.
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DOI：
10.1210/endo.139.1.5707
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发表时间：
1998
期刊：
影响因子：
4.8
通讯作者：
Li Ji Zhu;M. Bagchi;I. Bagchi
中科院分区：
文献类型：
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作者：
Li Ji Zhu;M. Bagchi;I. Bagchi
肽激素降钙素在许多组织（如骨和肾）中的钙稳态中起关键作用。我们以前的研究表明，降钙素的表达显着诱导大鼠子宫腺上皮细胞之间的第3-5天的怀孕前第5天的胚泡植入的发病。一旦植入进展到第6天，降钙素表达被关闭。时间上的巧合表明降钙素可能在导致着床的早期事件中作为子宫中的调节信号发挥作用。在这里，我们报告说，植入阶段特异性表达的降钙素可以特异性衰减管理针对降钙素信使RNA的外显子IV的反义寡核苷酸（ODNs）到子宫角在妊娠第2天。反义ODN治疗后降钙素信使RNA和蛋白表达的丧失伴随着胚胎植入的严重损害。基于以下观察结果：1）用具有不同碱基组成的两种不同反义ODNs处理产生相似的表型; 2）用互补正义ODNs处理不影响降钙素表达或植入，我们得出结论，反义ODNs对降钙素表达和植入的作用是特异性的且在功能上相关。我们的研究加强了这一假设，即降钙素在植入前期子宫的瞬时表达是至关重要的胚泡植入。
The peptide hormone calcitonin plays a key role in calcium homeostasis in many tissues, such as bone and kidney. Our previous studies revealed that the expression of calcitonin is dramatically induced in the glandular epithelium of rat uterus between days 3-5 of pregnancy before the onset of blastocyst implantation on day 5. Calcitonin expression is switched off once implantation has progressed to day 6. The coincidence in timing suggested that calcitonin may function as a regulatory signal in the uterus during the early events leading to implantation. Here we report that the implantation stage-specific expression of calcitonin can be specifically attenuated by administering antisense oligodeoxynucleotides (ODNs) directed against exon IV of calcitonin messenger RNA into the uterine horns on day 2 of gestation. The loss of calcitonin messenger RNA and protein expression upon antisense ODN treatment is accompanied by a severe impairment in implantation of embryos. Based on the observations that 1) treatment with two different antisense ODNs possessing different base compositions produced similar phenotypes; and 2) treatment with the complementary sense ODNs did not affect either calcitonin expression or implantation, we conclude that the effects of antisense ODNs on calcitonin expression and implantation are specific and functionally linked. Our study strengthens the hypothesis that a transient expression of calcitonin in the preimplantation phase uterus is critical for blastocyst implantation.