Endocrine Abstracts (2003) 6 P59

Vascular endothelial growth factor (VEGF), its receptors (KDR and Flt-1) and eNOS are up-regulated in the rat uterine cervix during pregnancy

CN Mowa1, S Jesmin2, I Sakuma2, Y Hattori3, H Togashi3, RE Papka1 & M Yoshioka3


1Neurobiol, NE Ohio Univ Coll Med, Rootstown,USA; 2Cardiovasc Med, Hokkaido Univ Med Sch, Sapporo, Japan; 3Pharmacol, Hokkaido Univ Med Sch, Sapporo, Japan.


The critical role played by local microvasculature in ovarian and uterine events during different functional states is well established. Surprisngly, little is known about the cervix, particularly the microvascular changes and roles associated with cervical ripening (a process of tissue remodeling, characterized by an inflammatory reaction, which facilitates passage of fetus at term). Because vascular remodeling is crucial in inflammatory responses it may (along with other factors, e.g. neuropeptides) play a critical role in cervical ripening. For this reason, the present study investigated expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR), endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF) in microvasculature of rat cervix before, during and after cervical ripening [day 8, 15, 20 and 22 of pregnancy and 2 day-postpartum (2dp)] using immunohistochemistry and Western blot analyses. VEGF was localized in the cervical stroma; Flt-1, eNOS and vWF were expressed mainly in the microvasculature of the cervical stroma, whereas KDR was largely located in the subepithelial endocervix of the cervix. VEGF levels, expressed as a percentage of day 8 levels, increased 200% at day 15 and 20, and only by 300% at day 22, but decreased to day 8 levels by 2dp (p<0.05). Changes in levels of Flt-1 and eNOS were simlar to those of VEGF (p<0.05). KDR levels increased 300% by day 15, 400% by day 20, 500% by day 22, and 300% by 2dp, when expressed as a percentage of day 8 levels (p<0.05). We conclude that the microvasculature of the cervix is dynamic and may play an important role in events associated with cervical ripening.

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