title: Potential role of intermedin/adrenomedullin 2 in early embryonic development in rats.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA. mschauha@utmb.edu
authors.forename: Madhu
authors.initials: M
authors.lastname: Chauhan
authors.forename: Rebekah
authors.initials: R
authors.lastname: Elkins
authors.forename: Meena
authors.initials: M
authors.lastname: Balakrishnan
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D053607:Adrenomedullin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D005260:Female; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology*; D036361:Peptide Hormones / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D009573:Nitrites; C000608036:PGF protein, human; D010446:Peptide Fragments; D036361:Peptide Hormones; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; C561869:intermedin (17-47); C467498:vascular endothelial growth factor A, rat; D000072483:Placenta Growth Factor; D053607:Adrenomedullin; D011374:Progesterone; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9