Profiles of cytokines secreted by isolated human endometrial cells under the influence of chorionic gonadotropin during the window of embryo implantation

Akhilesh Srivastava, Jayasree Sengupta, Alka Kriplani, Kallol K Roy, Debabrata Ghosh, Akhilesh Srivastava, Jayasree Sengupta, Alka Kriplani, Kallol K Roy, Debabrata Ghosh

Abstract

Background: Several studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin (hCG) may influence the implantation process by its action on human endometrial epithelial and stromal cells. Despite reports indicating that hCG acts on these cells to affect the production of several cytokines and growth factors (e.g., MIF, IGF-I, VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2), our understanding of the integral influence of hCG on paracrine interactions between endometrial stromal and epithelial cells during implantation is very limited.

Methods: In the present study, we examined the profile of 48 cytokines in the conditioned media of primary cell cultures of human implantation stage endometrium. Endometrial epithelial cells (group 1; n = 20), stromal cells (group 2; n = 20), and epithelial plus stromal cells (group 3; n = 20) obtained from mid-secretory stage endometrial samples (n = 60) were grown on collagen and exposed to different doses (0, 1, 10 and 100 IU/ml) of rhCG for 24 h in vitro. Immunochemical and qRT-PCR methods were used to determine cytokine profiles. Enrichment and process networks analyses were implemented using a list of cytokines showing differential secretion in response to hCG.

Results: Under basal conditions, endometrial epithelial and stromal cells exhibited cell type-specific profiles of secreted cytokines. Administration of hCG (100 IU) resulted in significantly (P < 0.05) different cytokine secretion profiles indicative of macropinocytic transport (HGF, MCSF) in epithelial cells, signal transduction (CCL4, FGF2, IL-1b, IL-6, IL-17, VEGF) in stromal cells, and epithelial-mesenchymal transition (FGF2, HGF, IL-1b, TNF) in mixed cells. Overall, the administration of hCG affected cytokines involved in the immune response, chemotaxis, inflammatory changes, proliferation, cell adhesion and apoptosis.

Conclusions: CG can influence the function of the endometrium during blastocyst implantation via its differential action on endometrial epithelial and stromal cells. CG may also affect complex paracrine processes in the different endometrial cell types.

Figures

Figure 1
Figure 1
Immunocytochemical characterisation of isolated endometrial cell populations in primary culture. Isolated human mid-luteal phase endometrial epithelial cells (A, D, G, J, M, P), stromal cells (B, E, H, K, N, Q) and mixed cells (C, F, I, L, O, R) were allowed to attach to the collagen biomatrix and subjected to immunostaining for cytokeratin (green;A-C), vimentin (red;D-F), CD45 (green; G-I), vW factor (red; J-L), and hCG binding (green; M-O) (detected with biotinylated rhCG) was determined in each cell type and in non-immune sera from mouse and goat (P) and non-immune sera from mouse and rabbit (Q) and biotinylated rhCG alone (R) followed by immunofluorescence detection was performed as described in the Methods section. Nuclei were counterstained with DAPI (blue). Bars = 50 μm.
Figure 2
Figure 2
Representative Western blot analysis of selected cytokines. Immunopositive images of CCL2, GMCSF, IL-6, LIF, PDGFBB and VEGF in conditioned media with isolated human endometrial epithelial cells (Group 1), stromal cells (Group 2) and mixed cells (Group 3) treated without or with rhCG (100 IU/ml) are shown. Conditioned media from different groups (20 μg of protein determined by Bradford assay) were subjected to electrophoretic separation followed by immunoblot analysis. The relative optical densities were measured by integrated image analysis per μg of protein.
Figure 3
Figure 3
Bar diagram showing fold increase in protein and transcript levels from cells treated in vitro with and without hCG. Fold increase in protein levels between cultures treated without or with rhCG (100 IU/ml) in conditioned media (grey bar) and relative abundance of transcripts (black bar) in cultured (A) endometrial epithelial cells, (B) endometrial stromal cells, and (C) endometrial mixed cells are shown. The pattern of regulation by hCG depending on cell type and cytokine is evident. For example, the protein level of CCL2 is high but shows very little change at the transcript level, whereas levels of IL-6 at both the protein and transcript level are high following rhCG treatment only in epithelial cells (A). Similarly, the protein levels of FGF2 and GMCSF are high but show very little change at the transcript level in stromal cells (B), whereas both protein and transcript levels are high in the mixed cells (C); these cytokines were unaffected in epithelial cells following hCG treatment. The pattern of changes in IFNG gene expression and protein secretion is very similar between endometrial stromal cells (B) and endometrial mixed cells (C) following administration of hCG.
Figure 4
Figure 4
A proposed model of the paracrine action mediated by hCG that involves different cell types in the endometrium and that affects the implantation-stage embryo and endometrium. The pre-implantation embryo- and endometrium-derived CG may specifically act on endometrial surface epithelium alone (A) or may act on both the endometrial epithelial cells and stromal fibroblasts (B), resulting in up-regulation of a specific cohort of cytokines, chemokines and growth factors. Many of these factors (e.g., CCL3, CCL4, CCL5, CXCL10, FGF2, GMCSF, IFNG, IL-1b, IL-6, IL-13, LIF, PDGFb, TNF and VEGF) are reportedly embryotropic, some (e.g., IL-6 and LIF) are primarily secreted by endometrial epithelial cells, and a few (e.g., FGF2, GMCSF, INFG, IL-1b and VEGF) are secreted primarily by endometrial fibroblasts in response to hCG. In contrast, many of the secreted factors are known to regulate stromal fibroblasts (e.g., FGF2, GCSF, GMCSF, IFNG, IL-1b, IL-6, LIF, MIF, TNF and TRAIL), vascular physiology (e.g., CCL2, CXCL10, GMCSF, IL-1b, IL-6, LIF, MIF, PDGFb, TNF and VEGF) and glandular physiology (e.g., LIF, MIF, PDGFb, and TNF). Only a few of the factors (e.g., CCL2, IL-6, LIF and MIF) are secreted by isolated endometrial epithelial cells in response to hCG. Interestingly, many of these factors directly and indirectly regulate the functions of immunocompetent cells. A large number of reports [21,32-53,57-78,80] and the results of the present study have been used to develop this model. BV (blood vessel), FB (fibroblast), GL (gland), IC (immunocompetent cells), PIE (pre-implantation embryo). There is no quantitative aspect to the length and thickness of arrows.

References

    1. Banerjee P, Fazleabas AT. Endometrial responses to embryonic signals in the primate. Int J Dev Biol. 2010;11:295–302. doi: 10.1387/ijdb.082829pb.
    1. Fishel SB, Edwards RG, Evans CJ. Human chorionic gonadotropin secreted by preimplantation embryos cultured in vitro. Science. 1984;11:816–818. doi: 10.1126/science.6546453.
    1. Jurisicova A, Antenos M, Kapasi K, Meriano J, Casper RF. Variability in the expression of trophectodermal markers beta-human chorionic gonadotrophin, human leukocyte antigen-G and pregnancy specific beta-1 glycoprotein by the human blastocyst. Hum Reprod. 1999;11:1852–1858. doi: 10.1093/humrep/14.7.1852.
    1. Zimmermann G, Ackermann W, Alexander H. Epithelial human chorionic gonadotropin is expressed and produced in human secretory endometrium during the normal menstrual cycle. Biol Reprod. 2009;11:1053–1065. doi: 10.1095/biolreprod.108.069575.
    1. Zimmermann G, Ackermann W, Alexander H. Expression and production of human chorionic gonadotropin (hCG) in the normal secretory endometrium: evidence of CGB7 and/or CGB6 beta hCG subunit gene expression. Biol Reprod. 2012;11:87. doi: 10.1095/biolreprod.111.092429.
    1. Licht P, von Wolff M, Berkholz A, Wildt L. Evidence for cycle-dependent expression of full-length human chorionic gonadotropin/luteinizing hormone receptor mRNA in human endometrium and decidua. Fertil Steril. 2003;11(Suppl 1):718–723.
    1. Perrier d’Hauterive S, Charlet-Renard C, Berndt S, Dubois M, Munaut C, Goffin F, Hagelstein MT, Noël A, Hazout A, Foidart JM, Geenen V. Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium. Hum Reprod. 2004;11:2633–2643. doi: 10.1093/humrep/deh450.
    1. Fazleabas AT, Donnelly KM, Srinivasan S, Fortman JD, Miller JB. Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity. Proc Natl Acad Sci U S A. 1999;11:2543–2548. doi: 10.1073/pnas.96.5.2543.
    1. Akoum A, Metz CN, Morin M. Marked increase in macrophage migration inhibitory factor synthesis and secretion in human endometrial cells in response to human chorionic gonadotropin hormone. J Clin Endocrinol Metab. 2005;11:2904–2910. doi: 10.1210/jc.2004-1900.
    1. Licht P, Russu V, Wildt L. On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: implications for differentiation and implantation. Semin Reprod Med. 2001;11:37–47. doi: 10.1055/s-2001-13909.
    1. Fluhr H, Bischof-Islami D, Krenzer S, Licht P, Bischof P, Zygmunt M. Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells. Fertil Steril. 2008;11(Suppl 4):1390–1395.
    1. Sherwin JR, Sharkey AM, Cameo P, Mavrogianis PM, Catalano RD, Edassery S, Fazleabas AT. Identification of novel genes regulated by chorionic gonadotropin in baboon endometrium during the window of implantation. Endocrinology. 2007;11:618–626.
    1. Fogle RH, Li A, Paulson RJ. Modulation of HOXA10 and other markers of endometrial receptivity by age and human chorionic gonadotropin in an endometrial explant model. Fertil Steril. 2010;11:1255–1259. doi: 10.1016/j.fertnstert.2008.11.002.
    1. Paiva P, Hannan NJ, Hincks C, Meehan KL, Pruysers E, Dimitriadis E, Salamonsen LA. Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Hum Reprod. 2011;11:1153–1162. doi: 10.1093/humrep/der027.
    1. Kajihara T, Uchino S, Suzuki M, Itakura A, Brosens JJ, Ishihara O. Human chorionic gonadotropin confers resistance to oxidative stress-induced apoptosis in decidualizing human endometrial stromal cells. Fertil Steril. 2011;11:1302–1307. doi: 10.1016/j.fertnstert.2010.05.048.
    1. Kajihara T, Tochigi H, Uchino S, Itakura A, Brosens JJ, Ishihara O. Differential effects of urinary and recombinant chorionic gonadotropin on oxidative stress responses in decidualizing human endometrial stromal cells. Placenta. 2011;11:592–597. doi: 10.1016/j.placenta.2011.05.002.
    1. Fluhr H, Ramp K, Krenzer S, Licht P, Zygmunt M. Inverse regulation of the interferon-gamma receptor and its signaling in human endometrial stromal cells during decidualization. Fertil Steril. 2009;11(Suppl 5):2131–2136.
    1. Bentin-Ley U, Pedersen B, Lindenberg S, Larsen JF, Hamberger L, Horn T. Isolation and culture of human endometrial cells in a three-dimensional culture system. J Reprod Fertil. 1994;11:327–332. doi: 10.1530/jrf.0.1010327.
    1. Ghosh D, Sengupta J. Morphological characteristics of human endometrial epithelial cells cultured on rat-tail collagen matrix. Hum Reprod. 1995;11:785–790.
    1. Evron A, Goldman S, Shalev E. Effect of primary human endometrial stromal cells on epithelial cell receptivity and protein expression is dependent on menstrual cycle stage. Hum Reprod. 2011;11:176–190. doi: 10.1093/humrep/deq296.
    1. COPE Cytokines & Cells Online Pathfinder EncyclopediaVersion 31.4. ]
    1. Ghosh D, Danielson KG, Alston JT, Heyner S. Functional differentiation of mouse uterine epithelial cells grown on collagen gels or reconstituted basement membranes. In Vitro Cell Dev Biol. 1991;11:713–719. doi: 10.1007/BF02633216.
    1. Sengupta J, Given RL, Carey JB, Weitlauf HM. Primary culture of mouse endometrium on floating collagen gels: a potential in vitro model for implantation. Ann N Y Acad Sci. 1986;11:75–94. doi: 10.1111/j.1749-6632.1986.tb20924.x.
    1. Sengupta J, Khan MA, Huppertz B, Ghosh D. In-vitro effects of the antimicrobial peptide Ala8,13,18-magainin II amide on isolated human first trimester villous trophoblast cells. Reprod Biol Endocrinol. 2011;11:49. doi: 10.1186/1477-7827-9-49.
    1. Sengupta S, Sengupta J, Mittal S, Kumar S, Ghosh D. Effect of human chorionic gonadotropin (hCG) on expression of vascular endothelial growth factor a (VEGF-a) in human mid-secretory endometrial cells in three-dimensional primary culture. Indian J Physiol Pharmacol. 2008;11:19–30.
    1. de Jager W, Rijkers GT. Solid-phase and bead-based cytokine immunoassay: a comparison. Methods. 2006;11:294–303. doi: 10.1016/j.ymeth.2005.11.008.
    1. Khan MA, Sengupta J, Mittal S, Ghosh D. Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis. Reprod Biol Endocrinol. 2012;11:84. doi: 10.1186/1477-7827-10-84.
    1. Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;11:3. doi: 10.1186/1471-2199-7-3.
    1. MetaCorebio manual 5.0. .
    1. Bentin-Ley U, Lopata A. In vitro models of human blastocyst implantation. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;11:765–774. doi: 10.1053/beog.2000.0117.
    1. Lalitkumar PG, Lalitkumar S, Meng CX, Stavreus-Evers A, Hambiliki F, Bentin-Ley U, Gemzell-Danielsson K. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Hum Reprod. 2007;11:3031–3037. doi: 10.1093/humrep/dem297.
    1. Tanaka T, Miyama M, Masuda M, Mizuno K, Sakamoto T, Umesaki N, Ogita S. Production and physiological function of granulocyte colony-stimulating factor in non-pregnant human endometrial stromal cells. Gynecol Endocrinol. 2000;11:399–404. doi: 10.3109/09513590009167710.
    1. Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertil Steril. 2011;11:2123.e13–2123.e17.
    1. Dimitriadis E, White CA, Jones RL, Salamonsen LA. Cytokines, chemokines and growth factors in endometrium related to implantation. Hum Reprod Update. 2005;11:613–630. doi: 10.1093/humupd/dmi023.
    1. Fahey JV, Schaefer TM, Channon JY, Wira CR. Secretion of cytokines and chemokines by polarized human epithelial cells from the female reproductive tract. Hum Reprod. 2005;11:1439–1446. doi: 10.1093/humrep/deh806.
    1. Guzeloglu-Kayisli O, Kayisli UA, Taylor HS. The role of growth factors and cytokines during implantation: endocrine and paracrine interactions. Semin Reprod Med. 2009;11:62–79. doi: 10.1055/s-0028-1108011.
    1. Hannan NJ, Stoikos CJ, Stephens AN, Salamonsen LA. Depletion of high-abundance serum proteins from human uterine lavages enhances detection of lower-abundance proteins. J Proteome Res. 2009;11:1099–1103. doi: 10.1021/pr800811y.
    1. Boomsma CM, Kavelaars A, Eijkemans MJ, Amarouchi K, Teklenburg G, Gutknecht D, Fauser BJ, Heijnen CJ, Macklon NS. Cytokine profiling in endometrial secretions: a non-invasive window on endometrial receptivity. Reprod Biomed Online. 2009;11:85–94. doi: 10.1016/S1472-6483(10)60429-4.
    1. Licht P, Lösch A, Dittrich R, Neuwinger J, Siebzehnrübl E, Wildt L. Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis. Hum Reprod Update. 1998;11:532–538. doi: 10.1093/humupd/4.5.532.
    1. Nasu K, Matsui N, Narahara H, Tanaka Y, Miyakawa I. Effects of interferon-gamma on cytokine production by endometrial stromal cells. Hum Reprod. 1998;11:2598–2601. doi: 10.1093/humrep/13.9.2598.
    1. Nasu K, Narahara H, Matsui N, Kawano Y, Tanaka Y, Miyakawa I. Platelet-activating factor stimulates cytokine production by human endometrial stromal cells. Mol Hum Reprod. 1999;11:548–553. doi: 10.1093/molehr/5.6.548.
    1. Lebovic DI, Chao VA, Martini JF, Taylor RN. IL-1beta induction of RANTES (regulated upon activation, normal T cell expressed and secreted) chemokine gene expression in endometriotic stromal cells depends on a nuclear factor-kappaB site in the proximal promoter. J Clin Endocrinol Metab. 2001;11:4759–4764. doi: 10.1210/jc.86.10.4759.
    1. Akoum A, Kong J, Metz C, Beaumont MC. Spontaneous and stimulated secretion of monocyte chemotactic protein-1 and macrophage migration inhibitory factor by peritoneal macrophages in women with and without endometriosis. Fertil Steril. 2002;11:989–994. doi: 10.1016/S0015-0282(02)03082-0.
    1. Caballero-Campo P, Domínguez F, Coloma J, Meseguer M, Remohí J, Pellicer A, Simón C. Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation. Mol Hum Reprod. 2002;11:375–384. doi: 10.1093/molehr/8.4.375.
    1. Kang J, Akoum A, Chapdelaine P, Laberge P, Poubelle PE, Fortier MA. Independent regulation of prostaglandins and monocyte chemoattractant protein-1 by interleukin-1beta and hCG in human endometrial cells. Hum Reprod. 2004;11:2465–2473. doi: 10.1093/humrep/deh458.
    1. Cao WG, Morin M, Metz C, Maheux R, Akoum A. Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NF-kappaB. Biol Reprod. 2005;11:565–570. doi: 10.1095/biolreprod.104.038331.
    1. Cao WG, Morin M, Sengers V, Metz C, Roger T, Maheux R, Akoum A. Tumour necrosis factor-alpha up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-kappaB. Hum Reprod. 2006;11:421–428.
    1. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Hiraki K, Sekine I, Matsuyama T, Ishimaru T. Interleukin-6- and tumour necrosis factor alpha-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis. Hum Reprod. 2005;11:2715–2723. doi: 10.1093/humrep/dei156.
    1. Roberts M, Luo X, Chegini N. Differential regulation of interleukins IL-13 and IL-15 by ovarian steroids, TNF-alpha and TGF-beta in human endometrial epithelial and stromal cells. Mol Hum Reprod. 2005;11:751–760. doi: 10.1093/molehr/gah233.
    1. Kitaya K, Yasuo T, Yamaguchi T, Fushiki S, Honjo H. Genes regulated by interferon-gamma in human uterine microvascular endothelial cells. Int J Mol Med. 2007;11:689–697.
    1. Kawano Y, Fukuda J, Nasu K, Matsumoto H, Narahara H, Miyakawa I. Synergistic effect of interleukin (IL)-1alpha and ceramide analogue on the production of IL-6, IL-8, and macrophage colony-stimulating factor by endometrial stromal cells. Fertil Steril. 2004;11(Suppl 3):1043–1047.
    1. Kawano Y, Furukawa Y, Kawano Y, Nasu K, Narahara H. Thrombin-induced chemokine production in endometrial stromal cells. Hum Reprod. 2011;11:407–413. doi: 10.1093/humrep/deq347.
    1. Robertson SA, Seamark RF. Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. Reprod Fertil Dev. 1992;11:435–448. doi: 10.1071/RD9920435.
    1. Ishiwata I, Tokieda Y, Kiguchi K, Sato K, Ishikawa H. Effects of embryotrophic factors on the embryogenesis and organogenesis of mouse embryos in vitro. Hum Cell. 2000;11:185–195.
    1. Orsi NM, Ekbote UV, Walker JJ, Gopichandran N. Uterine and serum cytokine arrays in the mouse during estrus. Anim Reprod Sci. 2007;11:301–310. doi: 10.1016/j.anireprosci.2006.08.016.
    1. Boomsma CM, Kavelaars A, Eijkemans MJ, Lentjes EG, Fauser BC, Heijnen CJ, Macklon NS. Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Hum Reprod. 2009;11:1427–1435. doi: 10.1093/humrep/dep011.
    1. Bourdiec A, Shao R, Rao CV, Akoum A. Human chorionic gonadotropin triggers angiogenesis via the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism underlying embryo implantation. Biol Reprod. 2012;11:66. doi: 10.1095/biolreprod.112.100370.
    1. Selam B, Kayisli UA, Akbas GE, Basar M, Arici A. Regulation of FAS ligand expression by chemokine ligand 2 in human endometrial cells. Biol Reprod. 2006;11:203–209. doi: 10.1095/biolreprod.105.045716.
    1. Kitaya K, Nakayama T, Daikoku N, Fushiki S, Honjo H. Spatial and temporal expression of ligands for CXCR3 and CXCR4 in human endometrium. J Clin Endocrinol Metab. 2004;11:2470–2476. doi: 10.1210/jc.2003-031293.
    1. Rainczuk A, Rao J, Gathercole J, Stephens AN. The emerging role of CXC chemokines in epithelial ovarian cancer. Reproduction. 2012;11:303–317. doi: 10.1530/REP-12-0153.
    1. Möller B, Rasmussen C, Lindblom B, Olovsson M. Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle. Mol Hum Reprod. 2001;11:65–72. doi: 10.1093/molehr/7.1.65.
    1. Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004;11:1738–1750. doi: 10.1095/biolreprod.103.024109.
    1. Sjöblom C, Roberts CT, Wikland M, Robertson SA. Granulocyte-macrophage colony-stimulating factor alleviates adverse consequences of embryo culture on fetal growth trajectory and placental morphogenesis. Endocrinology. 2005;11:2142–2153. doi: 10.1210/en.2004-1260.
    1. Boomsma CM, Kavelaars A, Eijkemans MJ, Fauser BC, Heijnen CJ, Macklon NS. Ovarian stimulation for in vitro fertilization alters the intrauterine cytokine, chemokine, and growth factor milieu encountered by the embryo. Fertil Steril. 2010;11:1764–1768. doi: 10.1016/j.fertnstert.2009.10.044.
    1. Masuhiro K, Matsuzaki N, Nishino E, Taniguchi T, Kameda T, Li Y, Saji F, Tanizawa O. Trophoblast-derived interleukin-1 (IL-1) stimulates the release of human chorionic gonadotropin by activating IL-6 and IL-6-receptor system in first trimester human trophoblasts. J Clin Endocrinol Metab. 1991;11:594–601. doi: 10.1210/jcem-72-3-594.
    1. Li Y, Matsuzaki N, Masuhiro K, Kameda T, Taniguchi T, Saji F, Yone K, Tanizawa O. Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6-receptor-dependent system in the normal human trophoblasts. J Clin Endocrinol Metab. 1992;11:184–191. doi: 10.1210/jc.74.1.184.
    1. Uzumcu M, Coskun S, Jaroudi K, Hollanders JM. Effect of human chorionic gonadotropin on cytokine production from human endometrial cells in vitro. Am J Reprod Immunol. 1998;11:83–88. doi: 10.1111/j.1600-0897.1998.tb00395.x.
    1. Arruvito L, Giulianelli S, Flores AC, Paladino N, Barboza M, Lanari C, Fainboim L. NK cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis. J Immunol. 2008;11:5746–5753.
    1. Lai T, Wang K, Hou Q, Zhang J, Yuan J, Yuan L, You Z, Xi M. Interleukin 17 induces up-regulation of chemokine and cytokine expression via activation of the nuclear factor κB and extracellular signal-regulated kinase 1/2 pathways in gynecologic cancer cell lines. Int J Gynecol Cancer. 2011;11:1533–1539. doi: 10.1097/IGC.0b013e31822d2abd.
    1. Hatayama H, Kanzaki H, Iwai M, Kariya M, Fujimoto M, Higuchi T, Kojima K, Nakayama H, Mori T, Fujita J. Progesterone enhances macrophage colony-stimulating factor production in human endometrial stromal cells in vitro. Endocrinology. 1994;11:1921–1927. doi: 10.1210/en.135.5.1921.
    1. Tanaka T, Sakamoto T, Umesaki N, Ogita S. Regulation of human endometrial stromal decidualization by macrophage colony-stimulating factor. Gynecol Obstet Invest. 2001;11:124–127. doi: 10.1159/000052907.
    1. Arcuri F, Ricci C, Ietta F, Cintorino M, Tripodi SA, Cetin I, Garzia E, Schatz F, Klemi P, Santopietro R, Paulesu L. Macrophage migration inhibitory factor in the human endometrium: expression and localization during the menstrual cycle and early pregnancy. Biol Reprod. 2001;11:1200–1205. doi: 10.1095/biolreprod64.4.1200.
    1. Lalitkumar PG, Sengupta J, Ghosh D. Endometrial tumor necrosis factor alpha (TNFalpha) is a likely mediator of early luteal phase mifepristone-mediated negative effector action on the preimplantation embryo. Reproduction. 2005;11:323–335. doi: 10.1530/rep.1.00433.
    1. Haider S, Knöfler M. Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta. 2009;11:111–123. doi: 10.1016/j.placenta.2008.10.012.
    1. Sengupta J, Lalitkumar PG, Najwa AR, Charnock-Jones DS, Evans AL, Sharkey AM, Smith SK, Ghosh D. Immunoneutralization of vascular endothelial growth factor inhibits pregnancy establishment in the rhesus monkey (Macaca mulatta) Reproduction. 2007;11:1199–1211. doi: 10.1530/rep.1.01228.
    1. Hannan NJ, Paiva P, Meehan KL, Rombauts LJF, Gardner DK, Salamonsen LA. Analysis of fertility-related soluble mediators in human uterine fluid identifies VEGF as a key regulator of embryo implantation. Endocrinology. 2011;11:4948–4956. doi: 10.1210/en.2011-1248.
    1. Berndt S, Perrier d’Hauterive S, Blacher S, Péqueux C, Lorquet S, Munaut C, Applanat M, Hervé MA, Lamandé N, Corvol P, van den Brûle F, Frankenne F, Poutanen M, Huhtaniemi I, Geenen V, Noël A, Foidart JM. Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium. FASEB J. 2006;11:2630–2632. doi: 10.1096/fj.06-5885fje.
    1. Abbas MM, Evans JJ, Sykes PH, Benny PS. Modulation of vascular endothelial growth factor and thymidine phosphorylase in normal human endometrial stromal cells. Fertil Steril. 2004;11(Suppl 3):1048–1053.
    1. Edwards RG. Physiological and molecular aspects of human implantation. Hum Reprod. 1995;11(Suppl 2):1–13. doi: 10.1093/humrep/10.suppl_2.1.
    1. Perrier D’Hauterive S, Berndt S, Tsampalas M, Charlet-Renard C, Dubois M, Bourgain C, Hazout A, Foidart JM, Geenen V. Dialogue between blastocyst hCG and endometrial LH/hCG receptor: which role in implantation? Gynecol Obstet Invest. 2007;11:156–160. doi: 10.1159/000101740.
    1. Learn CA, Mizel SB, McCall CE. mRNA and protein stability regulate the differential expression of pro- and anti-inflammatory genes in endotoxin-tolerant THP-1 cells. J Biol Chem. 2000;11:12185–12193. doi: 10.1074/jbc.275.16.12185.
    1. Pratt JM, Petty J, Riba-Garcia I, Robertson DHL, Gaskell SJ, Oliver SG, Beynon RJ. Dynamics of protein turnover, a missing dimension in proteomics. Mol Cell Proteomics. 2002;11:579–591. doi: 10.1074/mcp.M200046-MCP200.
    1. Fournier ML, Paulson A, Pavelka N, Mosley AL, Gaudenz K, Bradford WD, Glynn E, Li H, Sardiu ME, Fleharty B, Seidel C, Florens L, Washburn MP. Delayed correlation of mRNA and protein expression in repamycin-treated cells and a role for Ggc1 in cellular sensitivity to repmycin. Mol Cell Proteomics. 2010;11:271–284. doi: 10.1074/mcp.M900415-MCP200.
    1. Kristensen AR, Gsponer J, Foster LJ. Protein synthesis rate is the predominant regulator of protein expression during differentiation. Mol Syst Biol. 2013;11:689. 10.1038/msb.2013.47.

Source: PubMed

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