Abstract
Background
The placenta plays an important role during pregnancy providing maternal blood supply from the uterus to the developing fetus. The structure and function of the placenta changes with gestation, as the fetus develops and its demands change. This study aims to elucidate changes in cytokine and chemokine gene expression throughout mid-to-late gestation in rat placenta.
Methods
Sprague Dawley rats were time-mated, and placentae were obtained from 6 pregnant dams at 4 different gestational periods: E14.25, E15.25, E17.25, and E20. Changes in placental gene expression were measured by microarray analysis. Differentially expressed inflammatory genes were functionally categorized by pathway analysis. To validate the microarray results, a subset of genes was analyzed by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort of 22 rats.
Results
Changes in messenger RNA (mRNA) expression of various cytokines, chemokines, and genes of the tumor growth factor (3 and tumor necrosis factor family were analyzed in rat placentae at E14.25, E15.25, E17.25, and E20. Forty-six genes were differentially expressed, and of these 21 genes had increased expression in late gestation (E20). The gestational age pattern of gene expression was confirmed by qPCR in the validation cohort.
Conclusion
The observed acute, prelabor changes in the expression of these genes during gestation warrant further investigation to elucidate their role in pregnancy and parturition.
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References
Sitras V, Fenton C, Paulssen R, Vartun A, Acharya G. Differences in gene expression between first and third trimester human placenta: a microarray study. PloS One. 2012;7(3):e33294.
Gu Y, Sun J, Groome LJ, Wang Y. Differential miRNA expression profiles between the first and third trimester human placentas. Am J Physiol Endocrinol Metab. 2013;304(8):E836–E843.
Tessier DR, Raha S, Holloway AC. Yockell-Lelievre J, Tayade C, Gruslin A. Characterization of immune cells and cytokine localization in the rat utero-placental unit mid- to late gestation. J Reprod Immunol. 2015;110:89–101.
Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta. 2006;27(8):794–798.
Szukiewicz D. Cytokines in placental physiology and disease. Mediators Inflamm. 2012;2012:640823.
Bell MJ, Hallenbeck JM, Gallo V. Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats. Pediatr Res. 2004;56(4):541–546.
Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi GN. The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Mol Psychiatry. 2006;11(1):47–55.
Wang Y, Zhang X, Zhang Y, Xu H, Fang G. Expression and localization of IL-18 in the hypothalamic-pituitary-ovarian axis of non-pregnant, pregnant, and abortive rats. J Reprod Immunol. 2011;92(1-2):45–53.
Boles JL, Ross MG, Beloosesky R, Desai M, Belkacemi L. Placental-mediated increased cytokine response to lipopolysac-charides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus. J Inflamm Res. 2012;5:67–75.
Soares MJ, Chakraborty D, Karim Rumi MA, Konno T, Renaud SJ. Rat placentation: an experimental model for investigating the hemochorial maternal-fetal interface. Placenta. 2012;33(4):233–243.
de Rijk EP, van Esch E, Flik G. Pregnancy dating in the rat: placental morphology and maternal blood parameters. Toxicol Pathol. 2002;30(2):271–282.
Vaswani K, Chan HW, Peiris HN, et al. Gestation Related Gene Expression of the Endocannabinoid Pathway in Rat Placenta. Mediators Inflam. 2015;2015:850471.
Vaswani K, Chan HW, Verma P, et al. The rat placental renin-angiotensin system - a gestational gene expression study. Reprod Biol Endocrino. 2015;13:89.
Vaswani K, Hum MW, Chan HW, et al. The effect of gestational age on angiogenic gene expression in the rat placenta. PloS One. 2013;8(12):e83762.
Hebisch G, Neumaier-Wagner PM, Huch R, von Mandach U. Maternal serum interleukin-1 beta, -6 and -8 levels and potential determinants in pregnancy and peripartum. J Perinat Med. 2004;32(6):475–480.
Sato TA, Gupta DK, Keelan JA, Marvin KW, Mitchell MD. Expression of interleukin-1 beta mRNA in murine uterine and gestational tissues: relationship with gestational age. Am J Reprod Immunol. 2001;46(6):413–419.
Mark PJ, Lewis JL, Jones ML, Keelan JA, Waddell BJ. The inflammatory state of the rat placenta increases in late gestation and is further enhanced by glucocorticoids in the labyrinth zone. Placenta. 2013;34(7):559–566.
Mitchell MD, Rice GE, Vaswani K, Kvaskoff D, Peiris HN. Differential regulation of ricosanoid and endocannabinoid production by inflammatory mediators in human choriodecidua. PloS One. 2016;11(2):e0148306.
Ren K, Torres R. Role of interleukin-1 beta during pain and inflammation. Brain Res Rev. 2009;60(1):57–64.
Brown NL, Alvi SA, Elder MG, Bennett PR, Sullivan MH. A spontaneous induction of fetal membrane prostaglandin production precedes clinical labour. J Endocrinol. 1998;157(2):R1–R6.
Kolinska J, Lisa V, Clark JA, et al. Constitutive expression of IL-18 and IL-18 R in differentiated IEC-6 cells: effect of TNF-alpha and IFN-gamma treatment. J Interferon Cytokine Res. 2008;28(5):287–296.
Li W, Yamamoto H, Kubo S, Okamura H. Modulation of innate immunity by IL-18. J Reprod Immunol. 2009;83(1-2):101–105.
Klimkiewicz-Blok D, Florjanski J, Zalewski J, Blok R. Analysis of the concentrations of interleukin 18 in amniotic fluid in the second and the third trimesters of pregnancy. Adv Clin Exp Med. 2013;22(5):699–703.
Ida A, Tsuji Y, Muranaka J, et al. IL-18 in pregnancy; the elevation of IL-18 in maternal peripheral blood during labour and complicated pregnancies. J Reprod Immunol. 2000;47(1):65–74.
Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians. 1996;108(5):374–381.
Elenkov IJ, Wilder RL, Bakalov VK, et al. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times. J Clin Endocrinol Metab. 2001;86(10):4933–4938.
Phillips TA, Ni J, Hunt JS. Cell-specific expression of B lymphocyte (APRIL, BLyS)- and Th2 (CD30L/CD153)-promoting tumor necrosis factor superfamily ligands in human placentas. J Leukoc Biol. 2003;74(1):81–87.
Romero R, Miranda J, Chaemsaithong P, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm pre-labor rupture ofmembranes. J Matern Fetal Neonatal Med. 2015;28(12):1394–1409.
Lonergan M, Aponso D, Marvin KW, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm. J Clin Endocrinol Metab. 2003;88(8):3835–3844.
Bizargity P, Del Rio R, Phillippe M, Teuscher C, Bonney EA. Resistance to lipopolysaccharide-induced preterm delivery mediated by regulatory T cell function in mice. Biol Reprod. 2009;80(5):874–881.
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Vaswani, K., Nitert, M.D., Chan, HW. et al. Mid-to-Late Gestational Changes in Inflammatory Gene Expression in the Rat Placenta. Reprod. Sci. 25, 222–229 (2018). https://doi.org/10.1177/1933719117741375
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DOI: https://doi.org/10.1177/1933719117741375