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Association of cord blood des-acyl ghrelin with birth weight, and placental GHS-R1 receptor expression in SGA, AGA, and LGA newborns

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Abstract

Although ghrelin in cord blood has been associated to birth weight, its role in fetal and postnatal growth has not been elucidated. The aim of this study was to analyze total ghrelin, acyl ghrelin (AG), and des-acyl ghrelin (DAG) in cord blood of newborns with idiopathic birth weight alterations, and to evaluate protein expression of placental GHS-R1, in order to investigate their correlation with birth weight and placental weight. We performed a cross-sectional comparative study in umbilical cord blood and placentas from healthy mothers of SGA, AGA, and LGA (small, adequate and large for gestational age) term newborns (n = 20 per group). Cord blood total ghrelin, AG, and DAG were measured by ELISA, and placental GHS-R1 expression was evaluated by Western blot. Cord blood DAG was higher in SGA compared to AGA newborns (902.1 ± 109.1 and 597.4 ± 58.2 pg/ml, respectively, p = 0.01) while LGA and AGA showed similar values (627.2 ± 76.4 pg/ml for LGA, p = 0.80). DAG negatively correlated with birthweight (r = −0.31, p = 0.02) and placental weight (r = −0.33, p = 0.02). No differences in AG or total ghrelin were found. GHS-R1 protein in placenta was not differentially expressed among SGA, AGA, and LGA. Our results suggest a role of DAG in intrauterine growth. Further studies are needed in order to elucidate the mechanisms by which DAG participates in fetal growth.

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References

  1. U.G. Das, G.D. Sysyn, Abnormal fetal growth: intrauterine growth retardation, small for gestational age, large for gestational age. Pediatr. Clin. North Am. 51(3), 639–654, viii (2004). doi:10.1016/j.pcl.2004.01.004

  2. J. Mairesse, J. Lesage, C. Breton, B. Breant, T. Hahn, M. Darnaudery, S.L. Dickson, J. Seckl, B. Blondeau, D. Vieau, S. Maccari, O. Viltart, Maternal stress alters endocrine function of the feto-placental unit in rats. Am. J. Physiol. Endocrinol. Metab. 292(6), E1526–1533 (2007). doi:10.1152/ajpendo.00574.2006

    Article  CAS  PubMed  Google Scholar 

  3. M. Manikkam, E.J. Crespi, D.D. Doop, C. Herkimer, J.S. Lee, S. Yu, M.B. Brown, D.L. Foster, V. Padmanabhan, Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology 145(2), 790–798 (2004). doi:10.1210/en.2003-0478

    Article  CAS  PubMed  Google Scholar 

  4. D.J. Barker, P.D. Gluckman, K.M. Godfrey, J.E. Harding, J.A. Owens, J.S. Robinson, Fetal nutrition and cardiovascular disease in adult life. Lancet 341(8850), 938–941 (1993). doi:10.1016/0140-6736(93)91224-A

    Article  CAS  PubMed  Google Scholar 

  5. A. Carrascosa, D. Yeste, A. Copil, L. Audi, M. Gusinye, E. Vicens-Calvet, M. Clemente, Fetal growth regulation and intrauterine growth retardation. J. Pediatr. Endocrinol. Metab. 17(Suppl 3), 435–443 (2004)

    PubMed  Google Scholar 

  6. N. Xita, A. Tsatsoulis, Fetal origins of the metabolic syndrome. Ann. N. Y. Acad. Sci. 1205, 148–155 (2010). doi:10.1111/j.1749-6632.2010.05658.x

    Article  PubMed  Google Scholar 

  7. H.A. de Boo, J.E. Harding, The developmental origins of adult disease (Barker) hypothesis. Aust. N. Z. J. Obstet. Gynaecol. 46(1), 4–14 (2006). doi:10.1111/j.1479-828X.2006.00506.x

    Article  PubMed  Google Scholar 

  8. S.M. Donahue, K.P. Kleinman, M.W. Gillman, E. Oken, Trends in birth weight and gestational length among singleton term births in the United States: 1990–2005. Obstet. Gynecol. 115(2 Pt 1), 357–364 (2010). doi:10.1097/AOG.0b013e3181cbd5f5

    Article  PubMed  PubMed Central  Google Scholar 

  9. O. Gualillo, J. Caminos, M. Blanco, T. Garcia-Caballero, M. Kojima, K. Kangawa, C. Dieguez, F. Casanueva, Ghrelin, a novel placental-derived hormone. Endocrinology 142(2), 788–794 (2001). doi:10.1210/endo.142.2.7987

    CAS  PubMed  Google Scholar 

  10. S. Kitamura, I. Yokota, H. Hosoda, Y. Kotani, J. Matsuda, E. Naito, M. Ito, K. Kangawa, Y. Kuroda, Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance. J. Clin. Endocrinol. Metab. 88(11), 5473–5477 (2003). doi:10.1210/jc.2002-021350

    Article  CAS  PubMed  Google Scholar 

  11. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa, Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762), 656–660 (1999). doi:10.1038/45230

    Article  CAS  PubMed  Google Scholar 

  12. J.P. Chanoine, K. De Waele, P. Walia, Ghrelin and the growth hormone secretagogue receptor in growth and development. Int. J. Obes. (Lond.) 33(Suppl 1), S48–52 (2009). doi:10.1038/ijo.2009.17

    Article  CAS  Google Scholar 

  13. T.D. Muller, R. Nogueiras, M.L. Andermann, Z.B. Andrews, S.D. Anker, J. Argente, R.L. Batterham, S.C. Benoit, C.Y. Bowers, F. Broglio, F.F. Casanueva, D. D’Alessio, I. Depoortere, A. Geliebter, E. Ghigo, P.A. Cole, M. Cowley, D.E. Cummings, A. Dagher, S. Diano, S.L. Dickson, C. Dieguez, R. Granata, H.J. Grill, K. Grove, K.M. Habegger, K. Heppner, M.L. Heiman, L. Holsen, B. Holst, A. Inui, J.O. Jansson, H. Kirchner, M. Korbonits, B. Laferrere, C.W. LeRoux, M. Lopez, S. Morin, M. Nakazato, R. Nass, D. Perez-Tilve, P.T. Pfluger, T.W. Schwartz, R.J. Seeley, M. Sleeman, Y. Sun, L. Sussel, J. Tong, M.O. Thorner, A.J. van der Lely, L.H. van der Ploeg, J.M. Zigman, M. Kojima, K. Kangawa, R.G. Smith, T. Horvath, M.H. Tschop, Ghrelin. Mol. Metab. 4(6), 437–460 (2015). doi:10.1016/j.molmet.2015.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. P.J. Delhanty, S.J. Neggers, A.J. van der Lely, Mechanisms in endocrinology: ghrelin: the differences between acyl- and des-acyl ghrelin. Eur. J. Endocrinol. 167(5), 601–608 (2012). doi:10.1530/EJE-12-0456

    Article  CAS  PubMed  Google Scholar 

  15. K.B. Chow, J. Sun, K.M. Chu, W. Tai Cheung, C.H. Cheng, H. Wise, The truncated ghrelin receptor polypeptide (GHS-R1b) is localized in the endoplasmic reticulum where it forms heterodimers with ghrelin receptors (GHS-R1a) to attenuate their cell surface expression. Mol. Cell. Endocrinol. 348(1), 247–254 (2012). doi:10.1016/j.mce.2011.08.034

    Article  PubMed  Google Scholar 

  16. E.E. Onal, P. Cinaz, Y. Atalay, C. Turkyilmaz, A. Bideci, A. Akturk, N. Okumus, S. Unal, E. Koc, E. Ergenekon, Umbilical cord ghrelin concentrations in small- and appropriate-for-gestational age newborn infants: relationship to anthropometric markers. J. Endocrinol. 180(2), 267–271 (2004). JOE05447 [pii]

    Article  CAS  PubMed  Google Scholar 

  17. J. Farquhar, M. Heiman, A.C. Wong, R. Wach, P. Chessex, J.P. Chanoine, Elevated umbilical cord ghrelin concentrations in small for gestational age neonates. J. Clin. Endocrinol. Metab. 88(9), 4324–4327 (2003). doi:10.1210/jc.2003-030265

    Article  CAS  PubMed  Google Scholar 

  18. S. Gnanapavan, B. Kola, S.A. Bustin, D.G. Morris, P. McGee, P. Fairclough, S. Bhattacharya, R. Carpenter, A.B. Grossman, M. Korbonits, The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metab. 87(6), 2988 (2002). doi:10.1210/jcem.87.6.8739

    Article  CAS  PubMed  Google Scholar 

  19. B. Telejko, M. Kuzmicki, A. Zonenberg, A. Modzelewska, K. Niedziolko-Bagniuk, A. Ponurkiewicz, N. Wawrusiewicz-Kurylonek, A. Nikolajuk, J. Szamatowicz, P. Laudanski, A. Kretowski, M. Gorska, Ghrelin in gestational diabetes: serum level and mRNA expression in fat and placental tissue. Exp. Clin. Endocrinol. Diabetes 118(2), 87–92 (2010). doi:10.1055/s-0029-1238313

    Article  CAS  PubMed  Google Scholar 

  20. S. Flores-Huerta, H. Martínez-Salgado, Birth weight of male and female infants born in hospitals affiliated with the Instituto Mexicano del Seguro Social. Bol. Med. Hosp. Infant. MEx 69(1), 30–39 (2012)

    Google Scholar 

  21. Z. Yu, S. Han, J. Zhu, X. Sun, C. Ji, X. Guo, Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS ONE 8(4), e61627 (2013). doi:10.1371/journal.pone.0061627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. E. Haeussner, C. Schmitz, F. von Koch, H.G. Frank, Birth weight correlates with size but not shape of the normal human placenta. Placenta 34(7), 574–582 (2013). doi:10.1016/j.placenta.2013.04.011

    Article  CAS  PubMed  Google Scholar 

  23. F. Ouyang, M. Parker, S. Cerda, C. Pearson, L. Fu, M.W. Gillman, B. Zuckerman, X. Wang, Placental weight mediates the effects of prenatal factors on fetal growth: the extent differs by preterm status. Obesity (Silver Spring) 21(3), 609–620 (2013). doi:10.1002/oby.20254

    Article  Google Scholar 

  24. J. Fuglsang, C. Skjaerbaek, U. Espelund, J. Frystyk, S. Fisker, A. Flyvbjerg, P. Ovesen, Ghrelin and its relationship to growth hormones during normal pregnancy. Clin. Endocrinol. (Oxf.) 62(5), 554–559 (2005). doi:10.1111/j.1365-2265.2005.02257.x

    Article  CAS  Google Scholar 

  25. J. Fuglsang, P. Sandager, N. Moller, S. Fisker, J. Frystyk, P. Ovesen, Peripartum maternal and foetal ghrelin, growth hormones, IGFs and insulin interrelations. Clin. Endocrinol. (Oxf.) 64(5), 502–509 (2006). doi:10.1111/j.1365-2265.2006.02498.x

    Article  CAS  Google Scholar 

  26. G. Valsamakis, D.C. Papatheodorou, A. Naoum, A. Margeli, I. Papassotiriou, E. Kapantais, G. Creatsas, S. Kumar, G. Mastorakos, Neonatal birth waist is positively predicted by second trimester maternal active ghrelin, a pro-appetite hormone, and negatively associated with third trimester maternal leptin, a pro-satiety hormone. Early Human Dev. 90(9), 487–492 (2014). doi:10.1016/j.earlhumdev.2014.07.001

    Article  CAS  Google Scholar 

  27. G.A. Martos-Moreno, V. Barrios, V. Barrios, M. Saenz de Pipaon, J. Pozo, I. Dorronsoro, M. Martinez-Biarge, J. Quero, Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism. Eur. J. Endocrinol. 161(3), 381–389 (2009). doi:10.1530/EJE-09-0193

    Article  CAS  PubMed  Google Scholar 

  28. P. Pirazzoli, M. Lanari, S. Zucchini, M. Gennari, U. Pagotto, R. De Iasio, R. Pasquali, A. Cassio, A. Cicognani, E. Cacciari, Active and total ghrelin concentrations in the newborn. J. Pediatr. Endocrinol. Metab. 18(4), 379–384 (2005)

    Article  CAS  PubMed  Google Scholar 

  29. S. Bellone, A. Rapa, D. Vivenza, A. Vercellotti, A. Petri, G. Radetti, J. Bellone, F. Broglio, E. Ghigo, G. Bona, Circulating ghrelin levels in the newborn are positively associated with gestational age. Clin. Endocrinol. (Oxf.) 60(5), 613–617 (2004). doi:10.1111/j.1365-2265.2004.02014.x

    Article  CAS  Google Scholar 

  30. D. Cortelazzi, V. Cappiello, P.S. Morpurgo, S. Ronzoni, M.S. Nobile De Santis, I. Cetin, P. Beck-Peccoz, A. Spada, Circulating levels of ghrelin in human fetuses. Eur. J. Endocrinol. 149(2), 111–116 (2003)

    Article  CAS  PubMed  Google Scholar 

  31. G. Rindi, V. Necchi, A. Savio, A. Torsello, M. Zoli, V. Locatelli, F. Raimondo, D. Cocchi, E. Solcia, Characterisation of gastric ghrelin cells in man and other mammals: studies in adult and fetal tissues. Histochem. Cell Biol. 117(6), 511–519 (2002). doi:10.1007/s00418-002-0415-1

    Article  CAS  PubMed  Google Scholar 

  32. I. Yokota, S. Kitamura, H. Hosoda, Y. Kotani, K. Kangawa, Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation. Endocr. J. 52(2), 271–276 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. N. Ohkawa, H. Shoji, T. Kitamura, H. Suganuma, N. Yoshikawa, M. Suzuki, T. Lee, K. Hisata, T. Shimizu, IGF-I, leptin and active ghrelin levels in very low birth weight infants during the first 8 weeks of life. Acta Paediatr. 99(1), 37–41 (2010). doi:10.1111/j.1651-2227.2009.01516.x

    CAS  PubMed  Google Scholar 

  34. T. Shimizu, T. Kitamura, N. Yoshikawa, H. Suganuma, K. Hisata, K. Tanaka, K. Shinohara, Y. Yamashiro, Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures. Arch. Dis. Child. Fetal Neonatal Ed. 92(4), F291–292 (2007). doi:10.1136/adc.2005.092379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. H. Sahin, T. Erener, E. Erginoz, M. Vural, B. Ilikkan, S. Kavuncuoglu, H. Yildiz, Y. Perk, The relationship of active ghrelin levels and intrauterine growth in preterm infants. Eur. J. Endocrinol. 166(3), 399–405 (2012). doi:10.1530/EJE-11-0607

    Article  CAS  PubMed  Google Scholar 

  36. S. Bellone, F. Prodam, S. Savastio, D. Avanzo, A. Pagani, L. Trovato, G.E. Walker, G. Genoni, G. Bona, Acylated/unacylated ghrelin ratio in cord blood: correlation with anthropometric and metabolic parameters and pediatric lifespan comparison. Eur. J. Endocrinol. 166(1), 115–120 (2012). doi:10.1530/EJE-11-0346

    Article  CAS  PubMed  Google Scholar 

  37. H. Ni, P. Walia, J.P. Chanoine, Ontogeny of acylated ghrelin degradation in the rat. Peptides 31(2), 301–306 (2010). doi:10.1016/j.peptides.2009.11.016

    Article  CAS  PubMed  Google Scholar 

  38. M. Tschop, D.L. Smiley, M.L. Heiman, Ghrelin induces adiposity in rodents. Nature 407(6806), 908–913 (2000). doi:10.1038/35038090

    Article  CAS  PubMed  Google Scholar 

  39. M. Papotti, C. Ghe, P. Cassoni, F. Catapano, R. Deghenghi, E. Ghigo, G. Muccioli, Growth hormone secretagogue binding sites in peripheral human tissues. J. Clin. Endocrinol. Metab. 85(10), 3803–3807 (2000). doi:10.1210/jcem.85.10.6846

    CAS  PubMed  Google Scholar 

  40. C. Gauna, P.J. Delhanty, L.J. Hofland, J.A. Janssen, F. Broglio, R.J. Ross, E. Ghigo, A.J. van der Lely, Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J. Clin. Endocrinol. Metab. 90(2), 1055–1060 (2005). doi:10.1210/jc.2004-1069

    Article  CAS  PubMed  Google Scholar 

  41. R. Kumar, A. Salehi, J.F. Rehfeld, P. Hoglund, E. Lindstrom, R. Hakanson, Proghrelin peptides: desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets. Regul. Pept. 164(2–3), 65–70 (2010). doi:10.1016/j.regpep.2010.06.005

    Article  CAS  PubMed  Google Scholar 

  42. F. Broglio, C. Gottero, F. Prodam, C. Gauna, G. Muccioli, M. Papotti, T. Abribat, A.J. Van Der Lely, E. Ghigo, Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J. Clin. Endocrinol. Metab. 89(6), 3062–3065 (2004). doi:10.1210/jc.2003-031964

    Article  CAS  PubMed  Google Scholar 

  43. R. Granata, F. Settanni, L. Biancone, L. Trovato, R. Nano, F. Bertuzzi, S. Destefanis, M. Annunziata, M. Martinetti, F. Catapano, C. Ghe, J. Isgaard, M. Papotti, E. Ghigo, G. Muccioli, Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 148(2), 512–529 (2007). doi:10.1210/en.2006-0266

    Article  CAS  PubMed  Google Scholar 

  44. M. Sato, K. Nakahara, S. Goto, H. Kaiya, M. Miyazato, Y. Date, M. Nakazato, K. Kangawa, N. Murakami, Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord. Biochem. Biophys. Res. Commun. 350(3), 598–603 (2006). doi:10.1016/j.bbrc.2006.09.088

    Article  CAS  PubMed  Google Scholar 

  45. V. Jain, A. Singhal, Catch up growth in low birth weight infants: striking a healthy balance. Rev. Endocr. Metab. Disord. 13(2), 141–147 (2012). doi:10.1007/s11154-012-9216-6

    Article  PubMed  Google Scholar 

  46. K. Fidanci, C. Meral, S. Suleymanoglu, O. Pirgon, F. Karademir, S. Aydinoz, H. Ozkaya, M. Gultepe, I. Gocmen, Ghrelin levels and postnatal growth in healthy infants 0–3 months of age. J. Clin. Res. Pediatr. Endocrinol. 2(1), 34–38 (2010). doi:10.4274/jcrpe.v2i1.34

    Article  PubMed  PubMed Central  Google Scholar 

  47. B.C. Gohlke, A. Huber, K. Hecher, R. Fimmers, P. Bartmann, C.L. Roth, Fetal insulin-like growth factor (IGF)-I, IGF-II, and ghrelin in association with birth weight and postnatal growth in monozygotic twins with discordant growth. J. Clin. Endocrinol. Metab. 90(4), 2270–2274 (2005). doi:10.1210/jc.2004-1192

    Article  CAS  PubMed  Google Scholar 

  48. G. Iniguez, K. Ong, V. Pena, A. Avila, D. Dunger, V. Mericq, Fasting and post-glucose ghrelin levels in SGA infants: relationships with size and weight gain at one year of age. J. Clin. Endocrinol. Metab. 87(12), 5830–5833 (2002). doi:10.1210/jc.2002-021206

    Article  CAS  PubMed  Google Scholar 

  49. F. Mendez-Ramirez, G. Barbosa-Sabanero, G. Romero-Gutierrez, J.M. Malacara, Ghrelin in small-for-gestational age (SGA) newborn babies: a cross-sectional study. Clin. Endocrinol. (Oxf.) 70(1), 41–46 (2009). doi:10.1111/j.1365-2265.2008.03278.x

    Article  CAS  Google Scholar 

  50. R. Barazzoni, M. Zanetti, C. Ferreira, P. Vinci, A. Pirulli, M. Mucci, F. Dore, M. Fonda, B. Ciocchi, L. Cattin, G. Guarnieri, Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J. Clin. Endocrinol. Metab. 92(10), 3935–3940 (2007). doi:10.1210/jc.2006-2527

    Article  CAS  PubMed  Google Scholar 

  51. A. Rodriguez, J. Gomez-Ambrosi, V. Catalan, M.J. Gil, S. Becerril, N. Sainz, C. Silva, J. Salvador, I. Colina, G. Fruhbeck, Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int. J. Obes. (Lond.) 33(5), 541–552 (2009). doi:10.1038/ijo.2009.40

    Article  CAS  Google Scholar 

  52. J.A. Dardzinska, S. Malgorzewicz, L. Kaska, M. Proczko, T. Stefaniak, M. Stankiewicz, Z. Sledzinski, Fasting and postprandial acyl and desacyl ghrelin levels in obese and non-obese subjects. Endokrynologia Polska 65(5), 377–381 (2014). doi:10.5603/EP.2014.0052

    Article  PubMed  Google Scholar 

  53. A. Benso, D.H. St-Pierre, F. Prodam, E. Gramaglia, R. Granata, A.J. van der Lely, E. Ghigo, F. Broglio, Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans. Eur. J. Endocrinol. 166(5), 911–916 (2012). doi:10.1530/EJE-11-0982

    Article  CAS  PubMed  Google Scholar 

  54. B. Ozcan, S.J. Neggers, A.R. Miller, H.C. Yang, V. Lucaites, T. Abribat, S. Allas, M. Huisman, J.A. Visser, A.P. Themmen, E.J. Sijbrands, P.J. Delhanty, A.J. van der Lely, Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels? Eur. J. Endocrinol. 170(6), 799–807 (2014). doi:10.1530/EJE-13-0347

    Article  PubMed  Google Scholar 

  55. P.J. Delhanty, Y. Sun, J.A. Visser, A. van Kerkwijk, M. Huisman, W.F. van Ijcken, S. Swagemakers, R.G. Smith, A.P. Themmen, A.J. van der Lely, Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS ONE 5(7), e11749 (2010). doi:10.1371/journal.pone.0011749

    Article  PubMed  PubMed Central  Google Scholar 

  56. H. Cederberg, U. Rajala, V.M. Koivisto, J. Jokelainen, H.M. Surcel, S. Keinanen-Kiukaanniemi, M. Laakso, Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention. Eur. J. Endocrinol. 165(2), 243–248 (2011). doi:10.1530/EJE-11-0334

    Article  CAS  PubMed  Google Scholar 

  57. B. Callaghan, J.B. Furness, Novel and conventional receptors for ghrelin, desacyl-ghrelin, and pharmacologically related compounds. Pharmacol. Rev. 66(4), 984–1001 (2014). doi:10.1124/pr.113.008433

    Article  CAS  PubMed  Google Scholar 

  58. C. Chiesa, J.F. Osborn, C. Haass, F. Natale, M. Spinelli, E. Scapillati, A. Spinelli, L. Pacifico, Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry? Clin. Chem. 54(3), 550–558 (2008). doi:10.1373/clinchem.2007.095299

    Article  CAS  PubMed  Google Scholar 

  59. I.F. Bocca-Tjeertes, J.M. Kerstjens, S.A. Reijneveld, K. Veldman, A.F. Bos, A.F. de Winter, Growth patterns of large for gestational age children up to age 4 years. Pediatrics 133(3), e643–649 (2014). doi:10.1542/peds.2013-0985

    Article  PubMed  Google Scholar 

  60. G. Mingrone, M. Manco, M.E. Mora, C. Guidone, A. Iaconelli, D. Gniuli, L. Leccesi, C. Chiellini, G. Ghirlanda, Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care 31(9), 1872–1876 (2008). doi:10.2337/dc08-0432

    Article  PubMed  PubMed Central  Google Scholar 

  61. L. Pacifico, E. Poggiogalle, F. Costantino, C. Anania, F. Ferraro, F. Chiarelli, C. Chiesa, Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome. Eur. J. Endocrinol. 161(6), 861–870 (2009). doi:10.1530/EJE-09-0375

    Article  CAS  PubMed  Google Scholar 

  62. F. Darendeliler, S. Poyrazoglu, F. Bas, O. Sancakli, G. Gokcay, Ghrelin levels are decreased in non-obese prepubertal children born large for gestational age. Eur. J. Endocrinol. 160(6), 951–956 (2009). doi:10.1530/EJE-08-0924

    Article  CAS  PubMed  Google Scholar 

  63. A. Rak-Mardyla, E. Gregoraszczuk, Effect of ghrelin on proliferation, apoptosis and secretion of progesterone and hCG in the placental JEG-3 cell line. Reprod. Biol. 10(2), 159–165 (2010). S1642-431X(12)60058-8 [pii]

    Article  PubMed  Google Scholar 

  64. J.L. Harrison, C.L. Adam, Y.A. Brown, J.M. Wallace, R.P. Aitken, R.G. Lea, D.W. Miller, An immunohistochemical study of the localization and developmental expression of ghrelin and its functional receptor in the ovine placenta. Reprod. Biol. Endocrinol. 5, 25 (2007). doi:10.1186/1477-7827-5-25

    Article  PubMed  PubMed Central  Google Scholar 

  65. A. Nonoshita, Y. Nishi, S. Takushima, M. Oshima, H. Hosoda, K. Kangawa, M. Kojima, H. Mifune, E. Tanaka, D. Hori, T. Kamura, Dynamics of placental ghrelin production and its receptor expression in a Dahl salt-sensitive rat model of intrauterine growth restriction. Placenta 31(5), 358–364 (2010). doi:10.1016/j.placenta.2010.02.013

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by research funds from University of Guanajuato (0095/13) and FOMIX Consejo Nacional de Ciencia y Tecnología (CONACYT)—Guanajuato State Government (GTO-2012-C03-195238). MLLVM was recipient of a postdoctoral Fellowship Scholarship from CONACYT (CVU: 217876). MIGD was recipient of a PhD CONACYT Scholarship (CVU: 217761). We are indebted to Dr. Cutberto Torres Torres, Dr. Gabriel Corona Martínez, and Dr. Olimpia Azpeitia for their invaluable support.

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Correspondence to Gloria Barbosa-Sabanero.

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This study was approved by the corresponding ethics committees, written informed consent was obtained from participants, and all procedures were performed according to the Mexican General Health Laws and the Declaration of Helsinki.

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González-Domínguez, M.I., Lazo-de-la-Vega-Monroy, ML., Zaina, S. et al. Association of cord blood des-acyl ghrelin with birth weight, and placental GHS-R1 receptor expression in SGA, AGA, and LGA newborns. Endocrine 53, 182–191 (2016). https://doi.org/10.1007/s12020-015-0833-1

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  • DOI: https://doi.org/10.1007/s12020-015-0833-1

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