Potential role of intermedin/adrenomedullin 2 in early embryonic development in rats.

Potential role of intermedin/adrenomedullin 2 in early embryonic development in rats.
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DOI:
10.1016/j.regpep.2011.05.011
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发表时间:
2011-10-10
影响因子:
--
通讯作者:
Yallampalli, Chandra
Yallampalli, Chandra
中科院分区:
其他
文献类型:
--
作者:
Chauhan, Madhu;Elkins, Rebekah;Balakrishnan, Meena;Yallampalli, Chandra

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肾上腺髓质素2 (ADM2),又称间质素(IMD),在人胎盘滋养细胞中表达,可促进妊娠前期HTR-8/SV-neo细胞的侵袭和迁移。最近,我们证明在妊娠大鼠中输注IMD拮抗剂会导致胎儿-胎盘生长受限,这表明IMD在维持妊娠成功中起着重要作用。因此,本研究旨在评估IMD在大鼠胚胎植入模型中是否具有功能作用。我们发现IMD mRNA在大鼠着床部位表达,其在胎盘中的表达在第15天显著高于第18 - 22天。从妊娠第3天开始输注IMD拮抗剂IMD17-47,可显著降低第9天着床部位的体重,降低血清17β-雌二醇、孕酮、一氧化氮水平,降低血清MMP2和MMP9明胶酶活性。此外,MMP2、MMP9、VEGF和PLGF蛋白的表达水平在IMD拮抗剂处理的大鼠着床部位显著下调。这项研究表明,IMD可能参与调节对胚胎着床和生长至关重要的因素,从而建立正常的大鼠妊娠。
Adrenomedullin2 (ADM2), also referred to as Intermedin (IMD) is expressed in trophoblast cells in human placenta and enhances the invasion and migration of first trimester HTR-8/SV-neo cells. Recently we demonstrated that infusion of IMD antagonist in pregnant rats causes feto-placental growth restriction suggesting a role for IMD in maintaining a successful pregnancy. Therefore, this study was undertaken to assess if IMD has a functional role in embryo implantation in a rat model. We show that IMD mRNA is expressed in rat implantation sites and its expression is significantly higher on day 15 in placenta compared to days 18 – 22. Infusion of IMD antagonist IMD17–47 from day 3 of pregnancy causes a significant decrease in the weights of day 9 implantation sites as well as serum levels of 17β-estradiol, progesterone, nitric oxide and serum MMP2 and MMP9 gelatinase activity. Further, expression of MMP2,MMP9, VEGF and PLGF protein levels are significantly downregulated in the implantation sites of IMD antagonist treated rats. This study suggests a potential involvement of IMD in regulating the factors that are critical for implantation and growth of the embryo and thus in establishment of normal rat pregnancy.
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