Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells

Authors: Delphine Benaitreau, Esther Dos Santos, Marie-Christine Leneveu, Philippe De Mazancourt, René Pecquery, Marie-Noëlle Dieudonné

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

Login to get access

Abstract

Background

In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation.

Results

We showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up-regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down-regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation.

Conclusion

Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.
Appendix
Available only for authorised users
Literature
1.
Carson DD, Bagchi I, Dey SK, Enders AC, Fazleabas AT, Lessey BA, Yoshinaga K: Embryo implantation. Dev Biol. 2000, 223 (2): 217-237. 10.1006/dbio.2000.9767.CrossRefPubMed
2.
3.
Evain-Brion D, Malassine A: Human placenta as an endocrine organ. Growth Horm IGF Res. 2003, 13: S34-37. 10.1016/S1096-6374(03)00053-4.CrossRefPubMed
4.
Coutifaris C, Kao LC, Sehdev HM, Chin U, Babalola GO, Blaschuk OW, Strauss JF: E-cadherin expression during the differentiation of human trophoblasts. Development. 1991, 113 (3): 767-777.PubMed
5.
Getsios S, Chen GT, MacCalman CD: Regulation of beta-catenin mRNA and protein levels in human villous cytotrophoblasts undergoing aggregation and fusion in vitro: correlation with E-cadherin expression. J Reprod Fertil. 2000, 119 (1): 59-68. 10.1530/reprod/119.1.59.CrossRefPubMed
6.
Chang C, Chen PT, Chang GD, Huang CJ, Chen H: Functional characterization of the placental fusogenic membrane protein syncytin. Biol Reprod. 2004, 71 (6): 1956-1962. 10.1095/biolreprod.104.033340.CrossRefPubMed
7.
Chen CP, Chen LF, Yang SR, Chen CY, Ko CC, Chang GD, Chen H: Functional characterization of the human placental fusogenic membrane protein syncytin 2. Biol Reprod. 2008, 79 (5): 815-823. 10.1095/biolreprod.108.069765.CrossRefPubMed
8.
Vargas A, Moreau J, Landry S, LeBellego F, Toufaily C, Rassart E, Lafond J, Barbeau B: Syncytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol. 2009, 392 (2): 301-318. 10.1016/j.jmb.2009.07.025.CrossRefPubMed
9.
Morrish DW, Bhardwaj D, Dabbagh LK, Marusyk H, Siy O: Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta. J Clin Endocrinol Metab. 1987, 65 (6): 1282-1290. 10.1210/jcem-65-6-1282.CrossRefPubMed
10.
Cronier L, Guibourdenche J, Niger C, Malassine A: Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast. Placenta. 1999, 20 (8): 669-676. 10.1053/plac.1999.0423.CrossRefPubMed
11.
Garcia-Lloret MI, Morrish DW, Wegmann TG, Honore L, Turner AR, Guilbert LJ: Demonstration of functional cytokine-placental interactions: CSF-1 and GM-CSF stimulate human cytotrophoblast differentiation and peptide hormone secretion. Exp Cell Res. 1994, 214 (1): 46-54. 10.1006/excr.1994.1232.CrossRefPubMed
12.
Malassine A, Cronier L: Hormones and human trophoblast differentiation: a review. Endocrine. 2002, 19 (1): 3-11. 10.1385/ENDO:19:1:3.CrossRefPubMed
13.
Shi QJ, Lei ZM, Rao CV, Lin J: Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts. Endocrinology. 1993, 132 (3): 1387-1395. 10.1210/en.132.3.1387.PubMed
14.
Leisser C, Saleh L, Haider S, Husslein H, Sonderegger S, Knofler M: Tumour necrosis factor-alpha impairs chorionic gonadotrophin beta-subunit expression and cell fusion of human villous cytotrophoblast. Mol Hum Reprod. 2006, 12 (10): 601-609. 10.1093/molehr/gal066.CrossRefPubMed
15.
Morrish DW, Bhardwaj D, Paras MT: Transforming growth factor beta 1 inhibits placental differentiation and human chorionic gonadotropin and human placental lactogen secretion. Endocrinology. 1991, 129 (1): 22-26. 10.1210/endo-129-1-22.CrossRefPubMed
16.
Campos DB, Palin MF, Bordignon V, Murphy BD: The 'beneficial' adipokines in reproduction and fertility. Int J Obes (Lond). 2008, 32 (2): 223-231. 10.1038/sj.ijo.0803719.CrossRef
17.
Cong L, Gasser J, Zhao J, Yang B, Li F, Zhao AZ: Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr Relat Cancer. 2007, 14 (3): 713-720. 10.1677/ERC-07-0065.CrossRefPubMed
18.
Hoggard N, Haggarty P, Thomas L, Lea RG: Leptin expression in placental and fetal tissues: does leptin have a functional role?. Biochem Soc Trans. 2001, 29 (Pt 2): 57-63. 10.1042/BST0290057.CrossRefPubMed
19.
Takemura Y, Osuga Y, Yamauchi T, Kobayashi M, Harada M, Hirata T, Morimoto C, Hirota Y, Yoshino O, Koga K, Yano T, Kadowaki T, Taketani Y: Expression of adiponectin receptors and its possible implication in the human endometrium. Endocrinology. 2006, 147 (7): 3203-3210. 10.1210/en.2005-1510.CrossRefPubMed
20.
Alfer J, Muller-Schottle F, Classen-Linke I, von Rango U, Happel L, Beier-Hellwig K, Rath W, Beier HM: The endometrium as a novel target for leptin: differences in fertility and subfertility. Mol Hum Reprod. 2000, 6 (7): 595-601. 10.1093/molehr/6.7.595.CrossRefPubMed
21.
Gonzalez RR, Simon C, Caballero-Campo P, Norman R, Chardonnens D, Devoto L, Bischof P: Leptin and reproduction. Hum Reprod Update. 2000, 6 (3): 290-300. 10.1093/humupd/6.3.290.CrossRefPubMed
22.
Magarinos MP, Sanchez-Margalet V, Kotler M, Calvo JC, Varone CL: Leptin promotes cell proliferation and survival of trophoblastic cells. Biol Reprod. 2007, 76 (2): 203-210. 10.1095/biolreprod.106.051391.CrossRefPubMed
23.
Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G: Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003, 52 (7): 1779-1785. 10.2337/diabetes.52.7.1779.CrossRefPubMed
24.
Yamauchi T, Hara K, Kubota N, Terauchi Y, Tobe K, Froguel P, Nagai R, Kadowaki T: Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord. 2003, 3 (4): 243-254. 10.2174/1568008033340090.CrossRefPubMed
25.
Tilg H, Moschen AR: Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006, 6 (10): 772-783. 10.1038/nri1937.CrossRefPubMed
26.
Fu Y, Luo N, Klein RL, Garvey WT: Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005, 46 (7): 1369-1379. 10.1194/jlr.M400373-JLR200.CrossRefPubMed
27.
Hada Y, Yamauchi T, Waki H, Tsuchida A, Hara K, Yago H, Miyazaki O, Ebinuma H, Kadowaki T: Selective purification and characterization of adiponectin multimer species from human plasma. Biochem Biophys Res Commun. 2007, 356 (2): 487-493. 10.1016/j.bbrc.2007.03.004.CrossRefPubMed
28.
Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423 (6941): 762-769. 10.1038/nature01705.CrossRefPubMed
29.
Caminos JE, Nogueiras R, Gallego R, Bravo S, Tovar S, Garcia-Caballero T, Casanueva FF, Dieguez C: Expression and regulation of adiponectin and receptor in human and rat placenta. J Clin Endocrinol Metab. 2005, 90 (7): 4276-4286. 10.1210/jc.2004-0930.CrossRefPubMed
30.
Benaitreau D, Dieudonne MN, Dos Santos E, Leneveu MC, Mazancourt P, Pecquery R: Antiproliferative effects of adiponectin on human trophoblastic cell lines JEG-3 and BeWo. Biol Reprod. 2009, 80 (6): 1107-1114. 10.1095/biolreprod.108.070573.CrossRefPubMed
31.
Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF: T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA. 2004, 101 (28): 10308-10313. 10.1073/pnas.0403382101.PubMedCentralCrossRefPubMed
32.
Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y: Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 2000, 102 (11): 1296-1301.CrossRefPubMed
33.
Thyfault JP, Hedberg EM, Anchan RM, Thorne OP, Isler CM, Newton ER, Dohm GL, deVente JE: Gestational diabetes is associated with depressed adiponectin levels. J Soc Gynecol Investig. 2005, 12 (1): 41-45. 10.1016/j.jsgi.2004.07.003.CrossRefPubMed
34.
Lu D, Yang X, Wu Y, Wang H, Huang H, Dong M: Serum adiponectin, leptin and soluble leptin receptor in pre-eclampsia. Int J Gynaecol Obstet. 2006, 95 (2): 121-126. 10.1016/j.ijgo.2006.06.015.CrossRefPubMed
35.
Cortelazzi D, Corbetta S, Ronzoni S, Pelle F, Marconi A, Cozzi V, Cetin I, Cortelazzi R, Beck-Peccoz P, Spada A: Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies. Clin Endocrinol (Oxf). 2007, 66 (3): 447-453. 10.1111/j.1365-2265.2007.02761.x.CrossRef
36.
Ringler GE, Strauss JF: In vitro systems for the study of human placental endocrine function. Endocr Rev. 1990, 11 (1): 105-123. 10.1210/edrv-11-1-105.CrossRefPubMed
37.
Wice B, Menton D, Geuze H, Schwartz AL: Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res. 1990, 186 (2): 306-316. 10.1016/0014-4827(90)90310-7.CrossRefPubMed
38.
Strauss JF, Kido S, Sayegh R, Sakuragi N, Gafvels ME: The cAMP signalling system and human trophoblast function. Placenta. 1992, 13 (5): 389-403. 10.1016/0143-4004(92)90047-W.CrossRefPubMed
39.
Handschuh K, Guibourdenche J, Tsatsaris V, Guesnon M, Laurendeau I, Evain-Brion D, Fournier T: Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells. Placenta. 2007, 28 (2-3): 175-184. 10.1016/j.placenta.2006.01.019.CrossRefPubMed
40.
Machinal-Quelin F, Dieudonne MN, Leneveu MC, Pecquery R, Giudicelli Y: Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways. Am J Physiol Cell Physiol. 2002, 282 (4): C853-863.CrossRefPubMed
41.
Bauche IB, Ait El Mkadem S, Rezsohazy R, Funahashi T, Maeda N, Miranda LM, Brichard SM: Adiponectin downregulates its own production and the expression of its AdipoR2 receptor in transgenic mice. Biochem Biophys Res Commun. 2006, 345 (4): 1414-1424. 10.1016/j.bbrc.2006.05.033.CrossRefPubMed
42.
Mistry T, Digby JE, Chen J, Desai KM, Randeva HS: The regulation of adiponectin receptors in human prostate cancer cell lines. Biochem Biophys Res Commun. 2006, 348 (3): 832-838. 10.1016/j.bbrc.2006.07.139.CrossRefPubMed
43.
Dos Santos E, Benaitreau D, Dieudonne MN, Leneveu MC, Serazin V, Giudicelli Y, Pecquery R: Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells. Oncol Rep. 2008, 20 (4): 971-977.PubMed
44.
Keryer G, Alsat E, Tasken K, Evain-Brion D: Cyclic AMP-dependent protein kinases and human trophoblast cell differentiation in vitro. J Cell Sci. 1998, 111: 995-1004.PubMed
45.
Castellucci M, De Matteis R, Meisser A, Cancello R, Monsurro V, Islami D, Sarzani R, Marzioni D, Cinti S, Bischof P: Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod. 2000, 6 (10): 951-958. 10.1093/molehr/6.10.951.CrossRefPubMed
46.
McDonald EA, Wolfe MW: Adiponectin attenuation of endocrine function within human term trophoblast cells. Endocrinology. 2009, 150 (9): 4358-4365. 10.1210/en.2009-0058.CrossRefPubMed
47.
Maruo T, Matsuo H, Murata K, Mochizuki M: Gestational age-dependent dual action of epidermal growth factor on human placenta early in gestation. J Clin Endocrinol Metab. 1992, 75 (5): 1362-1367. 10.1210/jc.75.5.1362.PubMed
48.
Zappala G, Rechler MM: IGFBP-3, hypoxia and TNF-alpha inhibit adiponectin transcription. Biochem Biophys Res Commun. 2009, 382 (4): 785-789. 10.1016/j.bbrc.2009.03.112.PubMedCentralCrossRefPubMed
49.
Maymo JL, Perez Perez A, Sanchez-Margalet V, Duenas JL, Calvo JC, Varone CL: Up-regulation of placental leptin by human chorionic gonadotropin. Endocrinology. 2009, 150 (1): 304-313. 10.1210/en.2008-0522.CrossRefPubMed
50.
Islami D, Bischof P, Chardonnens D: Possible interactions between leptin, gonadotrophin-releasing hormone (GnRH-I and II) and human chorionic gonadotrophin (hCG). Eur J Obstet Gynecol Reprod Biol. 2003, 110 (2): 169-175. 10.1016/S0301-2115(03)00185-4.CrossRefPubMed
51.
Cameo P, Bischof P, Calvo JC: Effect of leptin on progesterone, human chorionic gonadotropin, and interleukin-6 secretion by human term trophoblast cells in culture. Biol Reprod. 2003, 68 (2): 472-477. 10.1095/biolreprod.102.006122.CrossRefPubMed
52.
Dos Santos E, Dieudonne MN, Leneveu MC, Pecquery R, Serazin V, Giudicelli Y: In vitro effects of chorionic gonadotropin hormone on human adipose development. J Endocrinol. 2007, 194 (2): 313-325. 10.1677/JOE-06-0101.CrossRefPubMed
53.
Chabrolle C, Tosca L, Dupont J: Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007, 133 (4): 719-731. 10.1530/REP-06-0244.CrossRefPubMed
54.
Fiaschi T, Cirelli D, Comito G, Gelmini S, Ramponi G, Serio M, Chiarugi P: Globular adiponectin induces differentiation and fusion of skeletal muscle cells. Cell Res. 2009, 19 (5): 584-597. 10.1038/cr.2009.39.CrossRefPubMed
55.
Huppertz B, Kingdom JC: Apoptosis in the trophoblast--role of apoptosis in placental morphogenesis. J Soc Gynecol Investig. 2004, 11 (6): 353-362. 10.1016/j.jsgi.2004.06.002.CrossRefPubMed
56.
White L, Dharmarajan A, Charles A: Caspase-14: a new player in cytotrophoblast differentiation. Reprod Biomed Online. 2007, 14 (3): 300-307. 10.1016/S1472-6483(10)60871-1.CrossRefPubMed
57.
Black S, Kadyrov M, Kaufmann P, Ugele B, Emans N, Huppertz B: Syncytial fusion of human trophoblast depends on caspase 8. Cell Death Differ. 2004, 11 (1): 90-98. 10.1038/sj.cdd.4401307.CrossRefPubMed
58.
Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R: Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2006, 345 (1): 271-279. 10.1016/j.bbrc.2006.04.076.CrossRefPubMed
59.
Nien JK, Mazaki-Tovi S, Romero R, Erez O, Kusanovic JP, Gotsch F, Pineles BL, Gomez R, Edwin S, Mazor M, Espinoza J, Yoon BH, Hassan SS: Adiponectin in severe preeclampsia. J Perinat Med. 2007, 35 (6): 503-512. 10.1515/JPM.2007.121.PubMedCentralPubMed
Metadata
Title
Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells
Authors
Delphine Benaitreau
Esther Dos Santos
Marie-Christine Leneveu
Philippe De Mazancourt
René Pecquery
Marie-Noëlle Dieudonné
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-128

Other articles of this Issue 1/2010

Reproductive Biology and Endocrinology 1/2010 Go to the issue

Research

Proto-oncogene c-erbB2 initiates rat primordial follicle growth via PKC and MAPK pathways

Research

Downregulation of both gene expression and activity of Hsp27 improved maturation of mouse oocyte in vitro

Research

Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

Research

Gene expression profile of androgen modulated genes in the murine fetal developing lung

Research

Molecular characterization and expression of DERL1 in bovine ovarian follicles and corpora lutea

Research

Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome