Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis

Abstract

Vascular growth of the uterine cervix during pregnancy is associated with mast cell (MC) degranulation. To better understand the mechanism underlying this process, uterine cervices of intact pregnant rats were dissected and endothelial cell proliferation was measured by a bromodeoxyuridine incorporation technique. Total vascular endothelial growth factor (VEGF) mRNA expression and the relative abundance of VEGF splice variants (120, 164, and 188) were determined by RT-PCR. VEGF protein expression was evaluated by immunohistochemistry. To investigate the role of MCs on cervical angiogenesis, a second set of pregnant animals were treated with an MC stabilizer (disodium cromoglycate) to inhibit MC degranulation. Furthermore, 17b-estradiol (E 2 ) serum levels were established by RIA. In intact pregnant rats, VEGF mRNA expression was positively correlated with endothelial cell proliferation and circulating E 2 levels. All selected splice variants of VEGF gene were detected and their relative abundance did not show any change throughout pregnancy. Animals treated with disodium cromoglycate showed a decrease in endothelial cell proliferation and in VEGF mRNA expression compared with controls. Relative abundance of VEGF mRNA splice variants and E 2 serum levels showed no differences between these experimental groups. These results show a time-dependent correlation between VEGF mRNA expression and E 2 serum levels in the uterine cervix of intact pregnant rats, while MC stabilizer-treated animals reduced the VEGF expression without modifying E 2 serum levels. We suggest that cervical angiogenesis during pregnancy could be regulated by a mechanism which involves endogenous E 2 and chemical mediators stored in MC granules via a VEGFdependent pathway.

Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation

“…Until recently, their contribution to pregnancy establishment and/or maintenance was unclear as contradictory reports could be found in the literature. In pregnant rats, MC degranulation was shown to have positive effects on cervical angiogenesis (66). In mice, Menzies et al found no role for these cells in labor in a syngeneic context when employing C57BL/6J- Kit W-sh/W-sh mice (67).…”

Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats

“…The serum samples stored at −20°C were thawed, and the serum levels of E2 and P were determined by RIA after ethyl ether and hexane (Merck, Buenos Aires, Argentina) extraction, respectively (Bosquiazzo et al, 2007). The antibodies were provided by G. D. Niswender, and the labeled hormones were purchased from PerkinElmer Life and Analytical Sciences (Boston, MA, USA).…”

The Hidden Side of Disodium Cromolyn: from Mast Cell Stabilizer to an Angiogenic Factor and Antitumor Agent

“…Sapmaz et al (2015) reported that cromolyn treatment induced a significant reduction in VEGF-a in the lung parenchyma of the male Fischer 344 rats with aspiration-induced fibrosis (Chang et al 2014). Bosquiazzo et al (2007) used disodium cromoglycate to inhibit mast cells degranulation and, related to this, to study angiogenesis variability in rat uterine cervix during pregnancy. They reported an inhibition of VEGF mRNA by disodium cromolyn and also a decreased endothelial cell proliferation.…”