Nutrition and the IGF System in Reproduction

  • Frank A. Simmen
  • Inseok Kwak
  • Jason L. Blum
  • Rosalia C. M. Simmen
Part of the Nutrition and Health book series (NH)


  • Nutrition interacts with the IGF system to modify reproductive processes.

  • The relative roles of the circulating vs tissue IGF systems in nutritional control of reproduction remains to be elucidated.

  • There are profound species differences in IGF system expression and actions in reproduction.

  • Use of multiple models and approaches is required to elucidate fundamental aspects of IGFs in nutrition and reproduction of humans and domestic animals.


Estrous Cycle Corpus Luteum Dietary Energy Restriction Bovine Seminal Plasma 
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  1. 1.
    Wang H-S, Chard T. IGFs and IGF-binding proteins in the regulation of human ovarian and endometrial function. J Endocrinol 1999; 161: 1–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Drummond-Barbosa D, Spradling AC. Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol 2001; 231: 265–278.PubMedCrossRefGoogle Scholar
  3. 3.
    Thou J, Kumar TR, Matzuk MM, Bondy C. Insulin-like growth factor I regulates gonadotropin responsiveness in the mutine ovary. Mol Endocrinol 1997; 11: 1924–1933.CrossRefGoogle Scholar
  4. 4.
    Besnard N, Pisselet C, Zapf J, Hornebeck W, Monniaux D, Monget P. Proteolytic activity is involved in changes in intrafollicular insulin-like growth factor-binding protein levels during growth and atresia of ovine ovarian follicles. Endocrinology 1996; 137: 1599–1607.PubMedCrossRefGoogle Scholar
  5. 5.
    Besnard N, Pisselet C, Monniaux D, Monget P. Proteolytic activity degrading insulin-like growth factor-binding protein-2, -3, -4, and -5 in healthy growing and atretic follicles in the pig ovary. Biol Reprod 1997; 56: 1050–1058.PubMedCrossRefGoogle Scholar
  6. 6.
    Nakatani A, Shimasaki S, Erickson GF, Ling N. Tissue-specific expression of four insulin-like growth factor-binding proteins (1, 2, 3, and 4) in the rat ovary. Endocrinology 1991; 129: 1521–1529.PubMedCrossRefGoogle Scholar
  7. 7.
    Quesnel H, Pasquier A, Mounier AM, Prunier A. Influence of feed restriction during lactation on gonadotropic hormones and ovarian development in prinúparous sows. J Anim Sci 1998; 76: 856–863.PubMedGoogle Scholar
  8. 8.
    Bossis I, Wettemann RP, Welty SD, Vizcarra JA, Spicer LJ, Diskin MG. Nutritionally induced anovulation in beef heifers: ovarian and endocrine function preceding cessation of ovulation. J Anim Sci 1999; 77: 1536–1546.PubMedGoogle Scholar
  9. 9.
    Vandehaar MJ, Sharma BK, Fogwell RL. Effect of dietary energy restriction on the expression of insulin-like growth factor-I in liver and corpus luteum of heifers. J Dairy Sci 1995; 78: 832–841.PubMedCrossRefGoogle Scholar
  10. 10.
    O’Callaghan D, Yaakub H, Hyttel P, Spicer LJ, Boland MP. Effect of nutrition and superovulation on oocyte morphology, follicular fluid composition and systemic hormone concentrations in ewes. J Reprod Fertil 2000; 118: 303–313.PubMedCrossRefGoogle Scholar
  11. 11.
    Simmen FA, Simmen RCM, Geisert RD, Martinat-Botte F, Bazer FW, Terqui M. Differential expression, during the estrous cycle and pre-and postimplantation conceptus development, of messenger ribonucleic acids encoding components of the pig uterine insulin-like growth factor system. Endocrinology 1992; 130: 1547–1556.PubMedCrossRefGoogle Scholar
  12. 12.
    Giudice LC, Dsupin BA, Irwin JC, Eckert RL. Identification of insulin-like growth factor binding proteins in human oviduct. Fertil Steril 1992; 57: 294–301.PubMedGoogle Scholar
  13. 13.
    Carlsson B, Hillsjö T, Nilsson A, Törnell J, Billig H. Expression of insulin-like growth factor-I (IGF-I) in the rat Fallopian tube: possible autocrine and paracrine action of Fallopian tube-derived IGF-I on the Fallopian tube and on the preimplantation embryo. Endocrinology 1993; 133: 2031–2039.PubMedCrossRefGoogle Scholar
  14. 14.
    Erickson GF, Girvigian MR, Sadighian AR, Nakatani A, Ling N, Shimasaki S. Tissue specific and cyclic expression of insulin-like growth factor binding proteins -1, -2, -3, -4, -5, -6 in the rat oviduct. Endocrine 1995; 3: 667–676.PubMedCrossRefGoogle Scholar
  15. 15.
    Wiseman DL, Henricks DM, Eberhardt DM, Bridges WC. Identification and content of insulin-like growth factors in porcine oviductal fluid. Biol Reprod 1992; 47: 126–132.PubMedCrossRefGoogle Scholar
  16. 16.
    Stevenson KR, Wathes DC. Insulin-like growth factors and their binding proteins in the ovine oviduct during the oestrous cycle. J Reprod Fertil 1996; 108: 31–40.PubMedCrossRefGoogle Scholar
  17. 17.
    Geisert RD, Lee C-Y, Simmen FA, Zavy MT, Fliss AE, Bazer FW, Simmen RCM. Expression of messenger RNAs encoding insulin-like growth factor-I, -II, and insulin-like growth factor binding protein-2 in bovine endometrium during the estrous cycle and early pregnancy. Biol Reprod 1991; 45: 975–983.PubMedCrossRefGoogle Scholar
  18. 18.
    Girvigian MR, Nakatani A, Ling N, Shimasaki S, Erickson GF. Insulin-like growth factor-binding proteins show distinct patterns of expression in the rat uterus. Biol Reprod 1994; 51: 296–302.PubMedCrossRefGoogle Scholar
  19. 19.
    Stevenson KR, Gilmour RS, Wathes DC. Localization of insulin-like growth factor-I (IGF-I) and -II messenger ribonucleic acids and type 1 IGF receptors in the ovine uterus during the estrous cycle and early pregnancy. Endocrinology 1994; 134: 1655–1664.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou J, Dsupin BA, Giudice LC, Bondy CA. Insulin-like growth factor system gene expression in human endometrium during the menstrual cycle. J Clin Endocrinol Metab 1994; 79: 1723–1734.PubMedCrossRefGoogle Scholar
  21. 21.
    Cann CH, Fairclough RJ, Sutton R, Gow CB. Endometrial expression of mRNA encoding insulin-like growth factors I and II and IGF-binding proteins 1 and 2 in early pregnant ewes. J Reprod Fertil 1997; 111: 7–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Keller ML, Roberts AJ, Seidel GE Jr. Characterization of insulin-like growth factor-binding proteins in the uterus and conceptus during early conceptus elongation in cattle. Biol Reprod 1998; 59: 632–642PubMedCrossRefGoogle Scholar
  23. 23.
    Rutanen EM. Insulin-like growth factors in endometrial function. Gynecol Endocrinol 1998; 12: 399–406.PubMedCrossRefGoogle Scholar
  24. 24.
    Robinson RS, Mann GE, Gadd TS, Lamming GE, Wathes DC. The expression of the IGF system in the bovine uterus throughout the oestrous cycle and early pregnancy. J Endocrinol 2000; 165: 231–243.PubMedCrossRefGoogle Scholar
  25. 25.
    Murphy LJ, Ghahary A. Uterine IGF-I: regulation of expression and its role in estrogen-induced uterine proliferation. Endocr Rev 1990; 11: 443–453.PubMedCrossRefGoogle Scholar
  26. 26.
    Klotz DM, Curtis-Hewitt SC, Ciana P, Raviscioni M, Lindzey JK, Foley J, et al. Requirement of estrogen receptor-alpha in insulin-like growth factor-1(IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. J Biol Chem 2002; 277: 8531–8537.PubMedCrossRefGoogle Scholar
  27. 27.
    Badinga L, Song S, Simmen RCM, Clarke JB, Clemmons DR, Simmen FA. Complex mediation of uterine endometrial epithelial cell growth by insulin-like growth factor-II (IGF-II) and IGF-binding protein-2. J Mol Endocrinol 1999; 23: 277–285.PubMedCrossRefGoogle Scholar
  28. 28.
    Giudice LC. Multifaceted roles for IGFBP-1 in human endometrium during implantation and pregnancy. Ann N Y Acad Sci 1997; 828: 146–156.PubMedCrossRefGoogle Scholar
  29. 29.
    Sterle JA, Boyd C, Peacock JT, Koenigsfeld AT, Lamberson WR, Gerrard DE, Lucy MC. Insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein-2 and pregnancy-associated glycoprotein mRNA in pigs with somatotropin-enhanced fetal growth. J Endocrinol 1998; 159: 441–450.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee CY, Green ML, Simmen RCM, Simmen FA. Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) within the pig uterine lumen associated with peri-implantation conceptus development. J Reprod Fertil 1998; 112: 369–377.PubMedCrossRefGoogle Scholar
  31. 31.
    Peterson M, Ledgard AM, Hodgkinson SC. The proteolysis of insulin-like growth factor binding proteins in ovine uterine fluid. Reprod Fertil Dev 1998; 10: 309–314.PubMedCrossRefGoogle Scholar
  32. 32.
    Cann CH, Fairclough RJ, Browne CA, Gow CB. Uterine luminal content of insulin-like growth factor (IGF)-I and endometrial expression of mRNA encoding IGF-binding proteins 1 and 2 during the oestrus cycle and early pregnancy in the ewe. Reprod Fertil Dev 1998; 10: 155–163.PubMedCrossRefGoogle Scholar
  33. 33.
    Gibson JM, Aplin JD, White A, Westwood M. Regulation of IGF bioavailability in pregnancy. Mol Hum Reprod 2001; 7: 79–87.PubMedCrossRefGoogle Scholar
  34. 34.
    Adam CL, Findlay PA. Effect of nutrition on testicular growth and plasma concentrations of gonadotrophins, testosterone and insulin-like growth factor I (IGF-I) in pubertal male Soay sheep. J Reprod Fertil 1997; 111: 121–125.PubMedCrossRefGoogle Scholar
  35. 35.
    Plymate SR, Rosen CJ, Paulsen CA, Ware JL, Chen J, Vessella RE, Birnbaum RS. 1996. Proteolysis of insulin-like growth factor-binding protein-3 in the male reproductive tract. J Clin Endocrinol Metab 1996; 81: 618–624.CrossRefGoogle Scholar
  36. 36.
    Henricks DM, Kouba AJ, Lackey BR, Boone WR, Gray SL. Identification of insulin-like growth factor I in bovine seminal plasma and its receptor on spermatozoa: influence on sperm motility. Biol Reprod 1998; 59: 330–337.PubMedCrossRefGoogle Scholar
  37. 37.
    Lackey BR, Boone WR, Gray SL, Henricks DM. Computer-assisted sperm motion analysis of bovine sperm treated with insulin-like growth factor I and II: implications as motility regulators and chemokinetic factors. Arch Androl 1998; 41: 115–125.PubMedCrossRefGoogle Scholar
  38. 38.
    Hull KL, Harvey S. Growth hormone: a reproductive endocrine-paracrine regulator? Rev Reprod 2000; 5: 175–182.PubMedCrossRefGoogle Scholar
  39. 39.
    Funston RN, Moss GE, Roberts AJ. Insulin-like growth factor-I (IGF-I) and IGF-binding proteins in bovine sera and pituitaries at different stages of the estrous cycle. Endocrinology 1995; 136: 62–68.PubMedCrossRefGoogle Scholar
  40. 40.
    Roberts AJ, Nugent RA III, Klindt J, Jenkins TG. Circulating insulin-like growth factor I, insulin-like growth factor binding proteins, growth hormone, and resumption of estrus in postpartum cows subjected to dietary energy restriction. J Anim Sci 1997; 75: 1909–1917.PubMedGoogle Scholar
  41. 41.
    Sohlstrom A, Katsman A, Kind KL, Grant PA, Owens PC, Robinson JS, Owens JA. Effects of acute and chronic food restriction on the insulin-like growth factor axis in the guinea pig. J Endocrinol 1998; 157: 107–114.PubMedCrossRefGoogle Scholar
  42. 42.
    Rhoads RP, Greenwood PL, Bell AW, Boisclair YR. Nutritional regulation of the genes encoding the acid-labile subunit and other components of the circulating insulin-like growth factor system in the sheep. J Anim Sci 2000; 78: 2681–2689.PubMedGoogle Scholar
  43. 43.
    Danilovich N, Wernsing D, Coschigano KT, Kopchick JJ, Bartke A. Deficits in female reproductive function in GH-R-KO mice: role of IGF-I. Endocrinology 1999; 140: 2637–2640.PubMedCrossRefGoogle Scholar
  44. 44.
    Chandrashekar V, Bartke A, Awoniyi CA, Tsai-Morris CH, Dufau ML, Russell LD, Kopchick JJ. Testicular endocrine function in GH receptor gene disrupted mice. Endocrinology 2001; 142: 3443–3450.PubMedCrossRefGoogle Scholar
  45. 45.
    Baker J, Liu J-P, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993; 75: 73–82.PubMedGoogle Scholar
  46. 46.
    Baker J, Hardy MP, Zhou J, Bondy C, Lupu F, Bellvé AR, Efstratiadis A. Effects of an IGF] gene null mutation on mouse reproduction. Mol Endocrinol 1996; 10: 903–918.PubMedCrossRefGoogle Scholar
  47. 47.
    Yakar S, Liu J-L, Stannard B, Butler A, Accili D, Sauer B, LeRoith D. 1999. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 1999; 96: 7324–7329.CrossRefGoogle Scholar
  48. 48.
    Liu J-L, Yakar S, LeRoith D. Conditional knockout of mouse insulin-like growth factor-1 gene using the Cre/loxP system. Proc Soc Exp Biol Med 2000; 223: 344–351.PubMedCrossRefGoogle Scholar
  49. 49.
    Ueki I, Ooi GT, Tremblay ML, Hurst KR, Bach LA, Boisclair YR. Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc Natl Acad Sci USA 2000; 97: 6868–6873.PubMedCrossRefGoogle Scholar
  50. 50.
    Schneider MR, Lahm H, Wu M, Hoeflich A, Wolf E. Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins. FASEB J 2000; 14: 629–640.PubMedGoogle Scholar
  51. 51.
    Wood TL, Rogler LE, Czick ME, Schuller AGP, Pintar JE. Selective alterations in organ sizes with a targeted disruption of the insulin-like growth factor binding protein-2 gene. Mol Endocrinol 2000; 14: 1472–1482.PubMedCrossRefGoogle Scholar
  52. 52.
    Hoeflich A, Wu M, Mohan S, Föll J, Wanke R, Froehlich T, Arnold GJ, Lahm H, Kolb HJ, Wolf E. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal body weight gain. Endocrinology 1999; 140: 5488–5496.PubMedCrossRefGoogle Scholar
  53. 53.
    Gallaher BW, Breier BH, Keven CL, Harding JE, Gluckman PD. Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep. J Endocrinol 1998; 159: 501–508.PubMedCrossRefGoogle Scholar
  54. 54.
    Brameld JM, Mostyn A, Dandrea J, Stephenson TJ, Dawson JM, Buttery PJ, Symonds ME. Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle. J Endocrinol 2000; 167: 429–437.PubMedCrossRefGoogle Scholar
  55. 55.
    Vickers MH, Ikenasio BA, Breier BH. IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming Endocrinology 2001; 142: 3964–3973.PubMedCrossRefGoogle Scholar
  56. 56.
    Osgerby JC, Wathes DC, Howard D, Gadd TS. The effect of maternal undernutrition on ovine fetal growth. J Endocrinol 2002; 173: 131–141.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Frank A. Simmen
  • Inseok Kwak
  • Jason L. Blum
  • Rosalia C. M. Simmen

There are no affiliations available

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