Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening.
Bilateral neurectomy of the pelvic nerve (BLPN) that carries uterine cervix-related sensory nerves induces dystocia, and administration of its vasoactive neuropeptides induces changes in the cervical microvasculature, resembling those that occur in the ripening cervix. This study was designed to test the hypothesis that (a) the cervix of pregnant rats expresses vascular endothelial growth factor (VEGF) and components of the angiogenic signaling pathway [VEGF receptors (Flt-1, KDR), activity of protein kinase B, Akt (phosphorylated Akt), and endothelial nitric oxide synthase (eNOS)] and von Willebrand Factor (vWF) and that these molecules undergo changes with pregnancy, and (b) bilateral pelvic neurectomy (BLPN) alters levels of VEGF concentration in the cervix. Using RT-PCR and sequencing, two VEGF isoforms, 120 and 164, were identified in the rat cervix. VEGF, VEGF receptor-1 (Flt-1), eNOS, and vWF immunoreactivities (ir) were localized in the microvasculature of cervical stroma. Their protein levels increased during pregnancy but decreased to control levels by 2 days postpartum. VEGF receptor-2 (KDR)-ir was confined to the epithelium of the endocervix. BLPN downregulated levels of VEGF by a third. Therefore, the components of the angiogenic signaling pathway are expressed in the cervix and change over pregnancy. Furthermore, angiogenic and sensory neuronal factors may be important in regulating the dynamic microvasculature in the ripening cervix and may subsequently play a role in cervical ripening and the birth process.
Mowa
C N
CN
Dept. of Neurobiology, Northeastern Ohio Universities College of Medicine, 4209 State Rt. 44, Rootstown, OH 44272, USA. cnmowa@neoucom.edu
Jesmin
S
S
Sakuma
I
I
Usip
S
S
Togashi
H
H
Yoshioka
M
M
Hattori
Y
Y
Papka
R
R
D000818:Animals; D020070:Cervical Ripening / Q000378:metabolism*; D002584:Cervix Uteri / Q000098:blood supply / Q000294:innervation / Q000378:metabolism*; D003714:Denervation; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008833:Microcirculation; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D040301:Vascular Endothelial Growth Factor Receptor-2; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt