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Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

Effects of resistin on porcine ovarian follicle steroidogenesis in prepubertal animals: an in vitro study

Authors: Agnieszka Rak-Mardyła, Martyna Durak, Ewa Łucja Gregoraszczuk

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

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Abstract

Background

Resistin was first reported to be an adipocyte-specific hormone, but recent studies have indicated a connection between resistin and reproductive function. However, it is not yet known if resistin is expressed by the ovary and if it can affect steroidogenesis in ovarian follicles from prepubertal pigs.

Methods

In this study, using real time PCR, immunoblotting, and ELISA, we quantified resistin expression and concentration in maturing ovarian follicles (small, 3–4 mm; medium, 4–5 mm; large, 6–7 mm) collected from prepubertal pigs. In addition, the dose-responsive effects of recombinant human resistin (0.1, 1, 10, and 100 ng/ml) on steroid hormone (i.e., progesterone [P4], androstendione [A4], testosterone [T], and estradiol [E2]) secretion in culture medium and steroidogenic enzyme (i.e., CYP11A1, 3betaHSD, CYP17A1, 17betaHSD, and CYP19A1) expression in ovarian follicles were determined.

Results

We observed that resistin gene and protein expression increased significantly (P < 0.05) during follicular growth, with large follicles expressing the highest level of this adipokine. Recombinant resistin also increased P4, A4, and T secretion by up-regulating the steady state levels of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. Recombinant resistin had no effects on E2 secretion and CYP19A1 expression in ovarian follicles.

Conclusion

Our results show resistin expression in ovarian follicles from prepubertal pigs for the first time. We also show that recombinant resistin stimulates steroidogenesis in ovarian follicles by increasing the expression of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. The presence of resistin in the porcine ovary and its direct effects on steroidogenesis suggest that resistin is a new regulator of ovary function in prepubertal animals.
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Literature
1.
go back to reference Otero M, Lago R, Lago F, Casanueva FF, Dieguez C, Gómez-Reino JJ, Gualillo O: Leptin, from fat to inflammation: old questions and new insights. FEBS Lett. 2005, 579: 295-301. 10.1016/j.febslet.2004.11.024.CrossRefPubMed Otero M, Lago R, Lago F, Casanueva FF, Dieguez C, Gómez-Reino JJ, Gualillo O: Leptin, from fat to inflammation: old questions and new insights. FEBS Lett. 2005, 579: 295-301. 10.1016/j.febslet.2004.11.024.CrossRefPubMed
2.
go back to reference Trayhurn P, Wood IS: Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutri. 2004, 92: 347-355. 10.1079/BJN20041213.CrossRef Trayhurn P, Wood IS: Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutri. 2004, 92: 347-355. 10.1079/BJN20041213.CrossRef
3.
go back to reference Trayhurn P, Wood IS: Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans. 2005, 33: 1078-1081. 10.1042/BST20051078.CrossRefPubMed Trayhurn P, Wood IS: Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans. 2005, 33: 1078-1081. 10.1042/BST20051078.CrossRefPubMed
4.
go back to reference Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA: A family of tissue specific resistin-like molecules. Proc Natl Acad Sci U S A. 2001, 98: 502-506. 10.1073/pnas.98.2.502.PubMedCentralCrossRefPubMed Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA: A family of tissue specific resistin-like molecules. Proc Natl Acad Sci U S A. 2001, 98: 502-506. 10.1073/pnas.98.2.502.PubMedCentralCrossRefPubMed
5.
go back to reference McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S: Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab. 2002, 87: 2407-2410. 10.1210/jc.87.5.2407.CrossRefPubMed McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S: Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab. 2002, 87: 2407-2410. 10.1210/jc.87.5.2407.CrossRefPubMed
6.
go back to reference Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S: Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001, 50: 2199-2202. 10.2337/diabetes.50.10.2199.CrossRefPubMed Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S: Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001, 50: 2199-2202. 10.2337/diabetes.50.10.2199.CrossRefPubMed
7.
go back to reference Kim KH, Zhao L, Moon Y, Kang C, Sul HS: Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc Natl Acad Sci U S A. 2004, 101: 6780-6785. 10.1073/pnas.0305905101.PubMedCentralCrossRefPubMed Kim KH, Zhao L, Moon Y, Kang C, Sul HS: Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc Natl Acad Sci U S A. 2004, 101: 6780-6785. 10.1073/pnas.0305905101.PubMedCentralCrossRefPubMed
8.
go back to reference Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS: Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004, 53: 1671-1679. 10.2337/diabetes.53.7.1671.CrossRefPubMed Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS: Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004, 53: 1671-1679. 10.2337/diabetes.53.7.1671.CrossRefPubMed
9.
go back to reference Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patek HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature. 2001, 409: 307-312. 10.1038/35053000.CrossRefPubMed Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patek HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature. 2001, 409: 307-312. 10.1038/35053000.CrossRefPubMed
10.
go back to reference Lazar MA: Resistin- and obesity-associated metabolic diseases. Horm Metab Res. 2007, 39: 710-716. 10.1055/s-2007-985897.CrossRefPubMed Lazar MA: Resistin- and obesity-associated metabolic diseases. Horm Metab Res. 2007, 39: 710-716. 10.1055/s-2007-985897.CrossRefPubMed
11.
go back to reference Nogueiras R, Barreiro ML, Caminos JE, Gaytán F, Suominen JS, Navarro VM, Casanueva FF, Aguilar E, Toppari J, Diéguez C, Tena-Sempere M: Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors. J Cell Sci. 2004, 117: 3247-3257. 10.1242/jcs.01196.CrossRefPubMed Nogueiras R, Barreiro ML, Caminos JE, Gaytán F, Suominen JS, Navarro VM, Casanueva FF, Aguilar E, Toppari J, Diéguez C, Tena-Sempere M: Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors. J Cell Sci. 2004, 117: 3247-3257. 10.1242/jcs.01196.CrossRefPubMed
12.
go back to reference Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Diéguez CR: Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res. 2003, 11: 408-414. 10.1038/oby.2003.55.CrossRefPubMed Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Diéguez CR: Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res. 2003, 11: 408-414. 10.1038/oby.2003.55.CrossRefPubMed
13.
go back to reference Morash BA, Ur E, Wiesner G, Roy J, Willkinson M: Pituitary resistin gene expression: effects of age, gender and obesity. Neuroendocrinology. 2004, 79: 149-156. 10.1159/000077273.CrossRefPubMed Morash BA, Ur E, Wiesner G, Roy J, Willkinson M: Pituitary resistin gene expression: effects of age, gender and obesity. Neuroendocrinology. 2004, 79: 149-156. 10.1159/000077273.CrossRefPubMed
14.
go back to reference Seow KM, Juan CC, Wu LY, Hsu YP, Yang WM, Tsai YL, Hwang JL, Ho LT: Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance. Hum Reprod. 2004, 19: 48-53. 10.1093/humrep/deh010.CrossRefPubMed Seow KM, Juan CC, Wu LY, Hsu YP, Yang WM, Tsai YL, Hwang JL, Ho LT: Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance. Hum Reprod. 2004, 19: 48-53. 10.1093/humrep/deh010.CrossRefPubMed
15.
go back to reference Dafopoulos K, Sourlas D, Kallitsaris A, Pournaras S, Messinis IE: Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle. Fertil Steril. 2009, 92: 1389-1394. 10.1016/j.fertnstert.2008.07.1773.CrossRefPubMed Dafopoulos K, Sourlas D, Kallitsaris A, Pournaras S, Messinis IE: Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle. Fertil Steril. 2009, 92: 1389-1394. 10.1016/j.fertnstert.2008.07.1773.CrossRefPubMed
16.
go back to reference Maillard V, Froment P, Ramé C, Uzbekova S, Elis S, Dupont J: Expression and effect of resistin on bovine and rat granulosa cell steroidogenesis and proliferation. Reproduction. 2011, 141: 467-479. 10.1530/REP-10-0419.CrossRefPubMed Maillard V, Froment P, Ramé C, Uzbekova S, Elis S, Dupont J: Expression and effect of resistin on bovine and rat granulosa cell steroidogenesis and proliferation. Reproduction. 2011, 141: 467-479. 10.1530/REP-10-0419.CrossRefPubMed
17.
go back to reference Jones AM, Rodgers J, Antibus D, Knoop A, Bruot B, Marcinkiewicz J: Relative ovarian resistin expression in normal cycling rats and rats with cystic ovaries. Biol Reprod. 2009, 81 (1): 532- Jones AM, Rodgers J, Antibus D, Knoop A, Bruot B, Marcinkiewicz J: Relative ovarian resistin expression in normal cycling rats and rats with cystic ovaries. Biol Reprod. 2009, 81 (1): 532-
18.
go back to reference Spicer LJ, Schreiber NB, Lagaly DV, Aad PY, Douthit LB, Grado-Ahuir JA: Effect of resistin on granulosa and theca cell function in cattle. Anim Reprod Sci. 2011, 124: 19-27. 10.1016/j.anireprosci.2011.01.005.CrossRefPubMed Spicer LJ, Schreiber NB, Lagaly DV, Aad PY, Douthit LB, Grado-Ahuir JA: Effect of resistin on granulosa and theca cell function in cattle. Anim Reprod Sci. 2011, 124: 19-27. 10.1016/j.anireprosci.2011.01.005.CrossRefPubMed
19.
go back to reference Munir I, Yen HW, Baruth T, Tarkowski R, Azziz R, Magoffin DA, Jakimiuk AJ: Resistin stimulation of 17alpha-hydroxylase activity in ovarian theca cells in vitro: relevance to polycystic ovary syndrome. J Clin Endocrinol Metab. 2005, 90: 4852-4857. 10.1210/jc.2004-2152.CrossRefPubMed Munir I, Yen HW, Baruth T, Tarkowski R, Azziz R, Magoffin DA, Jakimiuk AJ: Resistin stimulation of 17alpha-hydroxylase activity in ovarian theca cells in vitro: relevance to polycystic ovary syndrome. J Clin Endocrinol Metab. 2005, 90: 4852-4857. 10.1210/jc.2004-2152.CrossRefPubMed
20.
go back to reference Adeghate E: An update on the biology and physiology of resistin. Cell Mol Life Sci. 2004, 61: 2485-2496. 10.1007/s00018-004-4083-2.CrossRefPubMed Adeghate E: An update on the biology and physiology of resistin. Cell Mol Life Sci. 2004, 61: 2485-2496. 10.1007/s00018-004-4083-2.CrossRefPubMed
21.
go back to reference Rak-Mardyla A, Gregoraszczuk EL: Expression of ghrelin and its receptor in porcine ovarian follicles collected from prepubertal and estrous cycle animals. J Physiol Pharmacol. 2012, 63: 195-199.PubMed Rak-Mardyla A, Gregoraszczuk EL: Expression of ghrelin and its receptor in porcine ovarian follicles collected from prepubertal and estrous cycle animals. J Physiol Pharmacol. 2012, 63: 195-199.PubMed
22.
go back to reference Gregoraszczuk EL, Rak A, Wójtowicz A, Ptak A, Wojciechowicz T, Nowak KW: GH and IGF-I increase leptin receptor expression in prepubertal pig ovaries: the role of leptin in steroid secretion and cell apoptosis. Acta Vet Hung. 2006, 54: 413-426. 10.1556/AVet.54.2006.3.12.CrossRefPubMed Gregoraszczuk EL, Rak A, Wójtowicz A, Ptak A, Wojciechowicz T, Nowak KW: GH and IGF-I increase leptin receptor expression in prepubertal pig ovaries: the role of leptin in steroid secretion and cell apoptosis. Acta Vet Hung. 2006, 54: 413-426. 10.1556/AVet.54.2006.3.12.CrossRefPubMed
23.
go back to reference Webb R, Garnsworthy PC, Gong JG, Armstrong DG: Control of follicular growth: local interactions and nutritional influences. J Anim Sci. 2004, 82 (Suppl): E63-E74.PubMed Webb R, Garnsworthy PC, Gong JG, Armstrong DG: Control of follicular growth: local interactions and nutritional influences. J Anim Sci. 2004, 82 (Suppl): E63-E74.PubMed
24.
go back to reference Sarkar M, Schilffarth S, Schams D, Meyer HH, Berisha B: The expression of leptin and its receptor during different physiological stages in the bovine ovary. Mol Reprod Dev. 2010, 77: 174-181.PubMed Sarkar M, Schilffarth S, Schams D, Meyer HH, Berisha B: The expression of leptin and its receptor during different physiological stages in the bovine ovary. Mol Reprod Dev. 2010, 77: 174-181.PubMed
25.
go back to reference Kikuchi N, Andoh K, Abe Y, Yamada K, Mizunuma H, Ibuki Y: Inhibitory action of leptin on early follicular growth differs in immature and adult female mice. Biol Reprod. 2001, 65: 66-71. 10.1095/biolreprod65.1.66.CrossRefPubMed Kikuchi N, Andoh K, Abe Y, Yamada K, Mizunuma H, Ibuki Y: Inhibitory action of leptin on early follicular growth differs in immature and adult female mice. Biol Reprod. 2001, 65: 66-71. 10.1095/biolreprod65.1.66.CrossRefPubMed
26.
go back to reference Duggal PS, Van Der Hoek KH, Milner CR, Ryan NK, Armstrong DT, Magoffin DA, Norman RJ: The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology. 2000, 141: 1971-1976. 10.1210/en.141.6.1971.PubMed Duggal PS, Van Der Hoek KH, Milner CR, Ryan NK, Armstrong DT, Magoffin DA, Norman RJ: The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology. 2000, 141: 1971-1976. 10.1210/en.141.6.1971.PubMed
27.
go back to reference Ruiz-Cortés ZT, Men T, Palin MF, Downey BR, Lacroix DA, Murphy BD: Porcine leptin receptor: molecular structure and expression in the ovary. Mol Reprod Dev. 2000, 56: 465-474. 10.1002/1098-2795(200008)56:4<465::AID-MRD4>3.0.CO;2-Q.CrossRefPubMed Ruiz-Cortés ZT, Men T, Palin MF, Downey BR, Lacroix DA, Murphy BD: Porcine leptin receptor: molecular structure and expression in the ovary. Mol Reprod Dev. 2000, 56: 465-474. 10.1002/1098-2795(200008)56:4<465::AID-MRD4>3.0.CO;2-Q.CrossRefPubMed
28.
go back to reference Nicklin LT, Robinson RS, Marsters P, Campbell BK, Mann GE, Hunter MG: Leptin in the bovine corpus luteum: receptor expression and effects on progesterone production. Mol Reprod Dev. 2007, 74: 724-729. 10.1002/mrd.20671.CrossRefPubMed Nicklin LT, Robinson RS, Marsters P, Campbell BK, Mann GE, Hunter MG: Leptin in the bovine corpus luteum: receptor expression and effects on progesterone production. Mol Reprod Dev. 2007, 74: 724-729. 10.1002/mrd.20671.CrossRefPubMed
29.
30.
go back to reference Chen YH, Lee MJ, Chang HH, Hung PF, Kao YH: 17 beta-estradiol stimulates resistin gene expression in 3 T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-alpha pathways. Endocrinology. 2006, 147: 4496-4504. 10.1210/en.2005-1655.CrossRefPubMed Chen YH, Lee MJ, Chang HH, Hung PF, Kao YH: 17 beta-estradiol stimulates resistin gene expression in 3 T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-alpha pathways. Endocrinology. 2006, 147: 4496-4504. 10.1210/en.2005-1655.CrossRefPubMed
31.
go back to reference Ling C, Kindblom J, Wennbo H, Billig H: Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. FEBS Lett. 2001, 507: 147-150. 10.1016/S0014-5793(01)02961-1.CrossRefPubMed Ling C, Kindblom J, Wennbo H, Billig H: Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. FEBS Lett. 2001, 507: 147-150. 10.1016/S0014-5793(01)02961-1.CrossRefPubMed
32.
go back to reference Delhanty PJ, Mesotten D, McDougall F, Baxter RC: Growth hormone rapidly induces resistin gene expression in white adipose tissue of spontaneous dwarf (SDR) rats. Endocrinology. 2002, 143: 2445-2448. 10.1210/en.143.6.2445.CrossRefPubMed Delhanty PJ, Mesotten D, McDougall F, Baxter RC: Growth hormone rapidly induces resistin gene expression in white adipose tissue of spontaneous dwarf (SDR) rats. Endocrinology. 2002, 143: 2445-2448. 10.1210/en.143.6.2445.CrossRefPubMed
33.
go back to reference Li M, Fisette A, Zhao XY, Deng JY, Mi J, Cianflone K: Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents. Int J Obes (Lond). 2009, 33: 424-439. 10.1038/ijo.2009.44.CrossRef Li M, Fisette A, Zhao XY, Deng JY, Mi J, Cianflone K: Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents. Int J Obes (Lond). 2009, 33: 424-439. 10.1038/ijo.2009.44.CrossRef
34.
go back to reference Dai MH, Xia T, Chen XD, Gan L, Feng SQ, Qiu H, Peng Y, Yang ZQ: Cloning and characterization of porcine resistin gene. Domest Anim Endocrinol. 2006, 30: 88-97. 10.1016/j.domaniend.2005.06.003.CrossRefPubMed Dai MH, Xia T, Chen XD, Gan L, Feng SQ, Qiu H, Peng Y, Yang ZQ: Cloning and characterization of porcine resistin gene. Domest Anim Endocrinol. 2006, 30: 88-97. 10.1016/j.domaniend.2005.06.003.CrossRefPubMed
35.
go back to reference Abbott DH, Dumesic DA, Francs S: Developmental origin of polycystic ovary syndrome - a hypothesis. J Endocrinol. 2002, 174: 1-5. 10.1677/joe.0.1740001.CrossRefPubMed Abbott DH, Dumesic DA, Francs S: Developmental origin of polycystic ovary syndrome - a hypothesis. J Endocrinol. 2002, 174: 1-5. 10.1677/joe.0.1740001.CrossRefPubMed
36.
go back to reference West C, Foster DL, Evans NP, Robinson J, Padmanabhan V: Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol. 2001, 185: 51-59. 10.1016/S0303-7207(01)00632-3.CrossRefPubMed West C, Foster DL, Evans NP, Robinson J, Padmanabhan V: Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol. 2001, 185: 51-59. 10.1016/S0303-7207(01)00632-3.CrossRefPubMed
37.
go back to reference Foecking EM, Levine JE: Effects of experimental hyperandrogenemia on the female rat reproductive axis: suppression of progesterone-receptor messenger RNA expression in the brain and blockade of luteinizing hormone surges. Gend Med. 2005, 2: 155-165. 10.1016/S1550-8579(05)80044-0.CrossRefPubMed Foecking EM, Levine JE: Effects of experimental hyperandrogenemia on the female rat reproductive axis: suppression of progesterone-receptor messenger RNA expression in the brain and blockade of luteinizing hormone surges. Gend Med. 2005, 2: 155-165. 10.1016/S1550-8579(05)80044-0.CrossRefPubMed
38.
go back to reference Sullivan SD, Moenter SM: Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder. Proc Natl Acad Sci U S A. 2004, 101: 7129-7134. 10.1073/pnas.0308058101.PubMedCentralCrossRefPubMed Sullivan SD, Moenter SM: Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder. Proc Natl Acad Sci U S A. 2004, 101: 7129-7134. 10.1073/pnas.0308058101.PubMedCentralCrossRefPubMed
Metadata
Title
Effects of resistin on porcine ovarian follicle steroidogenesis in prepubertal animals: an in vitro study
Authors
Agnieszka Rak-Mardyła
Martyna Durak
Ewa Łucja Gregoraszczuk
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-45

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