Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening.
Female; Animals; Immunohistochemistry; Pregnancy; Rats; Microcirculation; Phosphorylation; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Reverse Transcriptase Polymerase Chain Reaction; Cervical Ripening/*metabolism; Cervix Uteri/blood supply/innervation/*metabolism; Denervation; Nitric Oxide Synthase Type III; Nitric Oxide Synthase/biosynthesis; Protein Isoforms/biosynthesis/metabolism; Protein-Serine-Threonine Kinases/biosynthesis; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins/biosynthesis; Vascular Endothelial Growth Factor A/biosynthesis/*metabolism; Vascular Endothelial Growth Factor Receptor-2/biosynthesis; Wistar; Animal/*metabolism
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; Jesmin S; Sakuma I; Usip S; Togashi H; Yoshioka M; Hattori Y; Papka R
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
2004
2004-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1369/jhc.4A6455.2004" target="_blank" rel="noreferrer noopener">10.1369/jhc.4A6455.2004</a>
Sensory nerves and neuropeptides in uterine cervical ripening.
Animal; Animals; Calcitonin Gene-Related Peptide/biosynthesis; Capsaicin/pharmacology; Cervical Ripening/*metabolism; Cervix Uteri/*innervation/*metabolism; Complementary/metabolism; Female; Genetic; Immunohistochemistry; Labor; Messenger/metabolism; Neurokinin-1/biosynthesis; Neurons/metabolism; Neuropeptides/*biosynthesis; Nitric Oxide Synthase/biosynthesis; Obstetric; Plasmids/metabolism; Postpartum Period; Pregnancy; Rats; Receptors; RNA; Secretogranin II; Sprague-Dawley; Substance P/biosynthesis; Transcription
At the time of parturition (fetal delivery) the uterine cervix must "ripen," becoming soft, pliable, and dilated to accommodate the fetus' delivery. The fundamental processes underlying cervical ripening remain poorly understood. Knowledge that abundant autonomic and sensory nerves supply the uterine cervix, that transection of afferent nerves supplying the cervix blocks parturition, and that some of the changes in the cervix resemble those seen in inflammatory reactions suggests nerves may have a role in the cervical ripening changes. The present study utilized immunohistochemistry, plasma extravasation, and solution hybridization-nuclease protection assay to elucidate the complement of primary afferent nerves and some receptors in the rat cervix during pregnancy, and to determine if they may have roles in the ripening process at term. This study revealed an abundance of nerves associated with the cervical vasculature and myometrial smooth muscle containing immunoreactivity for substance P, calcitonin gene-related peptide, secretoneurin, and nitric oxide synthase throughout pregnancy. Many of these are small unmyelinated capsaicin-sensitive C-fibers. Substance P- (NK1-) and calcitonin gene-related peptide receptors were apparent on uterine cervix vasculature from pregnant, parturient, and postpartum rats. NK1 receptor mRNA was maximal at 20 days of pregnancy. Plasma extravasation of i.v. administered Evans Blue or Monastral Blue was most pronounced at parturition (shortly after NK1 mRNA is maximal); this was similar to plasma extravasation evoked by i.v. administration of substance P or capsaicin-treatment. This study revealed new data about the nervous system of the rat uterine cervix and that these nerves and their transmitters could very well be part of a neurogenic inflammatory process involved in cervical ripening.
Collins J J; Usip S; McCarson K E; Papka R E
Peptides
2002
2002-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0196-9781(01)00593-9" target="_blank" rel="noreferrer noopener">10.1016/s0196-9781(01)00593-9</a>