Maternal plasma levels of vascular endothelial growth factor and interleukin-6 in the term-pregnant and non-pregnant rats
Mohammed Alotaibi
Abstract
Female reproductive functions are associated with changes in the level of systemic cytokines which play pivotal roles during ovulation, development of corpus luteum, embryo implantation, and labor. Although many studies reported elevated level of VEGF during early pregnancy and IL-6 at the onset of labors, there is still incomplete elucidation of the level of these systemic cytokines in the very-late pregnancy or in the non-pregnant states. The purpose of this study was to determine the maternal plasma level of vascular endothelial growth factor (VEGF) and interleukin-6 (IL6) in the term-pregnant and non-pregnant rats to see if their levels are changed at the very end of pregnancy. Blood samples were collected from twelve termpregnant rats and compared by aged-matched seven non-pregnant rats. Plasma was separated carefully from all samples and the concentrations of VEGF and IL-6 were determined by ELISA techniques. The plasma concentration of VEGF was significantly higher in the non-pregnant rats (0.237 pg/ ml) than in the termpregnant (0.2 pg/ ml; P < 0.001). The plasma concentration of IL-6 was significantly higher in the term-pregnant rats (50.12 pg/ ml) than in the nonpregnant ones (40.19 pg/ ml; P < 0.05). These findings suggest that the level of VEGF is decreased few days before labor possibly to decrease the ovarian blood flow and to cause luteolysis while the level of IL-6 is increased at the end of pregnancy possibly to cause a local inflammation. Together, these changes are necessary to stimulate the onset of labor.
Keywords
References
Augustin HG. 2005. Angiogenesis in the female reproductive system. In: Clauss M, Breier G (Ed.). Mechanisms of Angiogenesis. Basel, Switzerland: Birkhäuser Basel. pp.35-52
Bergqvist A, Bruse C, Carlberg MCarlström K. 2001. Interleukin 1β, interleukin-6, and tumor necrosis factor-α in endometriotic tissue and in endometrium. Fertil Steril, 75:489-495.
Bowen J, Chamley L, Mitchell MKeelan J. 2002. Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion and roles in establishment of pregnancy in women. Placenta, 23:239-256.
Chakraborty I, Das SDey S. 1995. Differential expression of vascular endothelial growth factor and its receptor mRNAs in the mouse uterus around the time of implantation. J Endocrinol, 147:339-352.
Das S, Chakraborty I, Wang J, Dey SHoffman L. 1997. Expression of vascular endothelial growth factor (VEGF) and VEGF-receptor messenger ribonucleic acids in the peri-implantation rabbit uterus. Biol Reprod, 56:1390-1399.
Espey LL. 1980. Ovulation as an inflammatory reaction-a hypothesis. Biol Reprod, 22:73-106.
Ferrara N. 2004. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev, 25:581- 611.
Greig PC, Murtha AP, Jimmerson CJ, Herbert WN, Roitman-Johnson BAllen J. 1997. Maternal serum interleukin-6 during pregnancy and during term and preterm labor. Obstet Gynecol, 90:465-469.
Guerin LR, Prins JRRobertson SA. 2009. Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update, 15:517-535.
Harrison-Woolrych ML, Sharkey AM, CharnockJones DSmith S. 1995. Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol & Metab, 80:1853-1858.
Hess A, Hamilton A, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O, Mavrogianis P, Ferrer KKruessel J. 2007. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod, 76:102-117.
Hickey MFraser I. 2000. The structure of endometrial microvessels. Hum Reprod, 15:57-66.
Ishihara KHirano T. 2002. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev, 13:357-368.
Kaczmarek M, Kiewisz J, Schams DZiecik A. 2009. Expression of VEGF-receptor system in conceptus during peri-implantation period and endometrial and luteal expression of soluble VEGFR-1 in the pig. Theriogenology, 71:1298-1306.
Kashida S, Sugino N, Takiguchi S, Karube A, Takayama H, Yamagata Y, Nakamura YKato H. 2001. Regulation and role of vascular endothelial growth factor in the corpus luteum during midpregnancy in rats. Biol Reprod, 64:317-323.
Kothari P, Pestana R, Mesraoua R, Elchaki R, Khan KF, Dannenberg AJFalcone DJ. 2014. IL-6–mediated induction of matrix metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages. J Immunol, 192:349-357.
Ledingham M, Thomson A, Jordan F, Young A, Crawford MNorman J. 2001. Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition. Obstet Gynecol, 97:235-242.
Lockwood CJ, Murk WK, Kayisli UA, Buchwalder LF, Huang SJ, Arcuri F, Li M, Gopinath ASchatz F. 2010. Regulation of interleukin-6 expression in human decidual cells and its potential role in chorioamnionitis. Am J Pathol, 177:1755-1764.
Lyall F, Greer IA, Boswell FFleming R. 1997. Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre‐eclampsia. BJOG, 104:223-228.
Lygnos M, Pappa K, Papadaki H, Relakis C, Koumantakis E, Anagnou NEliopoulos G. 2006. Changes in maternal plasma levels of VEGF, bFGF, TGF-β1, ET-1 and sKL during uncomplicated pregnancy, hypertensive pregnancy and gestational diabetes. In Vivo, 20:157-163.
Mesiano S. 2004. Myometrial progesterone responsiveness and the control of human parturition. J Soc Gynecol Investig, 11:193-202.
Mitchell BFTaggart MJ. 2009. Are animal models relevant to key aspects of human parturition? Am J Physiol Regul Integr Comp Physiol, 297:R525-R545.
Mohr E, Serre K, Manz RA, Cunningham AF, Khan M, Hardie DL, Bird RMacLennan IC. 2009.
Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature. J Immunol, 182:2113-2123.
Molnár M, Romero RHertelendy F. 1993. Interleukin-1 and tumor necrosis factor stimulate arachidonic acid release and phospholipid metabolism in human myometrial cells. Am J Obstet Gynecol, 169:825-829.
Osman I, Young A, Ledingham MA, Thomson AJ, Jordan F, Greer IANorman JE. 2003. Leukocyte density and pro‐inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod, 9:41-45.
Pauli SA, Tang H, Wang J, Bohlen P, Posser R, Hartman T, Sauer MV, Kitajewski JZimmermann RC. 2005. The vascular endothelial growth factor (VEGF)/VEGF receptor 2 pathway is critical for blood vessel survival in corpora lutea of pregnancy in the rodent. Endocrinology, 146:1301-1311.
Ratajczak CK, Fay JCMuglia LJ. 2010. Preventing preterm birth: the past limitations and new potential of animal models. Dis Model Mech, 3:407-414.
Redmer DAReynolds LP. 1996. Angiogenesis in the ovary. Rev Reprod, 1:182-192.
Sennström MB, Ekman G, Westergren-Thorsson G, Malmström A, Byström B, Endrésen U, Mlambo N, Norman M, Ståbi BBrauner A. 2000. Human cervical ripening, an inflammatory process mediated by cytokines. Mol Hum Reprod, 6:375-381.
Shynlova O, Nedd‐Roderique T, Li Y, Dorogin ALye SJ. 2013. Myometrial immune cells contribute to term parturition, preterm labour and post‐partum involution in mice. J Cell Mol Med, 17:90-102.
Smith S. 1998. Angiogenesis, vascular endothelial growth factor and the endometrium. Hum Reprod Update, 4:509-519.
Sugino N, Kashida S, Karube-Harada A, Takiguchi SKato H. 2002. Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy. Reproduction, 123:379-387.
Szarka A, Rigó J, Lázár L, Bekő GMolvarec A. 2010a. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol, 11:1.
Szarka A, Rigó J, Lázár L, Bekő GMolvarec A. 2010b. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol, 11:59.
Tjwa M, Luttun A, Autiero MCarmeliet P. 2003. VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res, 314:5-14.
Turner M, Shaikh SGreenwood S. 2002. Secretion of interleukin-1β and interleukin-6 by fragments of Term Human Placental Villi: Signalling Pathways and effects of Tumour Necrosis factor α and Mode of Delivery. Placenta, 23:467-474. Vassiliadis S, Ranella A, Papadimitriou L, Makrygiannakis AAthanassakis I. 1998. Serum levels of pro-and anti-inflammatory cytokines in non-pregnant women, during pregnancy, labour and abortion. Mediators Inflamm, 7:69-72.
Von Wolff M, Thaler C, Zepf C, Becker V, Beier HStrowitzki T. 2002. Endometrial expression and secretion of interleukin-6 throughout the menstrual cycle. Gynecol Endocrinol, 16:121-129.
Wada Y, Ozaki H, Abe N, Mori A, Sakamoto K, Nagamitsu T, Nakahara TIshii K. 2013. Role of vascular endothelial growth factor in maintenance of pregnancy in mice. Endocrinology, 154:900-910.
Young A, Thomson AJ, Ledingham M, Jordan F, Greer IANorman JE. 2002. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod, 66:445-449.
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email