Skip to main content Accessibility help

Spontaneous intrauterine growth restriction due to increased litter size in the guinea pig programmes postnatal growth, appetite and adult body composition

  • D. M. Horton (a1) (a2), D. A. Saint (a2), J. A. Owens (a1) (a2), K. L. Kind (a1) (a3) and K. L. Gatford (a1) (a2)...


Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in the programming of increased appetite, adiposity and cardiometabolic diseases. Guinea pigs provide an alternate small animal model to rodents to investigate mechanisms underlying prenatal programming, being relatively precocial at birth, with smaller litter sizes and undergoing neonatal catch-up growth after IUGR. The current study, therefore, investigated postnatal consequences of spontaneous IUGR due to varying litter size in this species. Size at birth, neonatal, juvenile (post-weaning, 30–60 days) and adolescent (60–90 days) growth, juvenile and adolescent food intake, and body composition of young adults (120 days) were measured in 158 male and female guinea pigs from litter sizes of one to five pups. Compared with singleton pups, birth weight of pups from litters of five was reduced by 38%. Other birth size measures were reduced to lesser degrees with head dimensions being relatively conserved. Pups from larger litters had faster fractional neonatal growth and faster absolute and fractional juvenile growth rates (P<0.005 for all). Relationships of post-weaning growth, feed intakes and adult body composition with size at birth and neonatal growth rate were sex specific, with neonatal growth rates strongly and positively correlated with adiposity in males only. In conclusion, spontaneous IUGR due to large litter sizes in the guinea pig causes many of the programmed sequelae of IUGR reported in other species, including human. This may therefore be a useful model to investigate the mechanisms underpinning perinatal programming of hyperphagia, obesity and longer-term metabolic consequences.


Corresponding author

*Address for correspondence: Dr K. L. Gatford, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, SA 5005, Australia. (Email


Hide All
1. Barker, DJ, Hales, CN, Fall, CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993; 36, 6267.
2. Gluckman, PD, Hanson, MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305, 17331736.
3. Kind, KL, Simonetta, G, Clifton, PM, Robinson, JS, Owens, JA. Effect of maternal feed restriction on blood pressure in the adult guinea pig. Exp Physiol. 2002; 87, 469477.
4. Kind, KL, Simonetta, G, Clifton, PM, et al. Effect of maternal feed restriction on glucose tolerance in the adult guinea pig. Am J Physiol. 2003; 284, R140R152.
5. Kind, KL, Clifton, PM, Katsman, AI, et al. Restricted fetal growth and the response to dietary cholesterol in the guinea pig. Am J Physiol. 1999; 277, R1675R1682.
6. Bertin, E, Gangnerau, M, Bailbe, D, Portha, B. Glucose metabolism and beta-cell mass in adult offspring of rats protein and/or energy restricted during the last week of pregnancy. Am J Physiol. 1999; 277, E11E17.
7. Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol. 2000; 279, E83E87.
8. Fernandez-Twinn, DS, Wayman, A, Ekizoglou, S, et al. Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring. Am J Physiol. 2005; 288, 368373.
9. Ozanne, SE, Hales, CN. Poor fetal growth followed by rapid postnatal catch-up growth leads to premature death. Mech Ageing Dev. 2005; 126, 852854.
10. Woods, LL, Weeks, DA, Rasch, R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004; 65, 13391348.
11. Desai, M, Crowther, NJ, Lucas, A, Hales, CN. Organ-selective growth in the offspring of protein-restricted mothers. Br J Nutr. 1996; 76, 591603.
12. Bleker, OP, Buimer, M, van der Post, JAM, van der Veen, F. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index. Placenta. 2006; 27, 10521054.
13. Pardi, G, Marconi, AM, Cetin, I. Pathophysiology of intrauterine growth retardation: role of the placenta. Acta Paediatr Suppl. 1997; 423, 170172.
14. Simmons, R, Templeton, L, Gertz, S. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes. 2001; 50, 22792286.
15. Engelbregt, MJT, van Weissenbruch, MM, Lips, P, et al. Body composition and bone measurements in intra-uterine growth retarded and early postnatally undernourished male and female rats at the age of 6 months: comparison with puberty. Bone. 2004; 34, 180186.
16. Jansson, T, Lambert, GW. Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous activity in the rat at 3-4 months of age. J Hypertens. 1999; 17, 12391248.
17. Houdijk, E, Engelbregt, M, Popp-Snijders, C, Delemarre-Van der Waal, H. Endocrine regulation and extended follow up of longitudinal growth in intrauterine growth-retarded rats. J Endocrinol. 2000; 166, 599608.
18. Eriksson, JG, Forsen, T, Tuomilehto, J, Osmond, C, Barker, DJ. Size at birth, childhood growth and obesity in adult life. Int J Obes Relat Metab Disord. 2001; 25, 735740.
19. Eriksson, JG, Forsen, T, Tuomilehto, J, et al. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. Br Med J. 1999; 318, 427431.
20. Law, CM, Shiell, AW, Newsome, CA, et al. Fetal, infant and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation. 2002; 105, 10881092.
21. Fagerberg, B, Bondjers, L, Nilsson, P. Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at middle age: the Atherosclerosis and Insulin Resistance study. J Intern Med. 2004; 256, 254259.
22. Eckstein, P, McKeown, T. The influence of maternal age, parity and weight on litter size in the guinea-pig. J Endocrinol. 1955; 12, 115119.
23. Eckstein, P, McKeown, T, Record, RG. Variation in placental weight according to litter size in the guinea-pig. J Endocrinol. 1955; 12, 108114.
24. Engle, WA, Lemons, JA. Composition of the fetal and maternal guinea pig throughout gestation. Pediatr Res. 1986; 20, 11561160.
25. Arbeeny, CM, Nordin, C, Edelstein, D, et al. Hyperlipoproteinemia in spontaneous diabetic guinea pigs. Metabolism. 1989; 38, 895900.
26. Vannevel, J. Diabetes mellitus in a 3-year-old, intact, female guinea pig. Can Vet J. 1998; 39, 503.
27. Kind, KL, Roberts, CT, Sohlstrom, A, et al. Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig. Am J Physiol. 2005; 288, R119R126.
28. Roberts, CT, Sohlstrom, A, Kind, KL, et al. Maternal food restriction reduces the exchange surface area and increases the barrier thickness of the placenta in the guinea-pig. Placenta. 2001; 22, 177186.
29. Roberts, CT, Sohlstrom, A, Kind, KL, et al. Altered placental structure induced by maternal food restriction in guinea pigs: a role for circulating IGF-II and IGFBP-2 in the mother? Placenta . 2001; 22(Suppl. A), S77S82.
30. Gilbert, JS, Nijland, MJ. Sex differences in the developmental origins of hypertension and cardiorenal disease. Am J Physiol. 2008; 295, R1941R1952.
31. Sarr, O, Thompson, JA, Zhao, L, Lee, TY, Regnault, TRH. Low birth weight male guinea pig offspring display increased visceral adiposity in early adulthood. PLoS One. 2014; 9, e98433.
32. Palliser, HK, Kelleher, MA, Welsh, TN, Zakar, T, Hirst, JJ. Mechanisms leading to increased risk of preterm birth in growth-restricted guinea pig pregnancies. Reprod Sci. 2014; 21, 269276.
33. Turner, AJ, Trudinger, BJ. A modification of the uterine artery restriction technique in the guinea pig fetus produces asymmetrical ultrasound growth. Placenta. 2009; 30, 236240.
34. Ibsen, HL. Prenatal growth in guinea-pigs with special reference to environmental factors affecting weight at birth. J Exp Zool. 1928; 51, 5194.
35. McKeown, T, MacMahon, B. The influence of litter size and litter order on length of gestation and early postnatal growth in the guinea-pig. J Endocrinol. 1956; 13, 195200.
36. Sisk, DB. Physiology. In The Biology of the Guinea Pig (eds. Wagner J, Manning P), 1976; pp. 6398. Acedemic Press: New York.
37. Mittelman, SD, Van Citters, GW, Kirkman, EL, Bergman, RN. Extreme insulin resistance of the central adipose depot in vivo. Diabetes. 2002; 51, 755761.
38. Lim, KI, Yang, SJ, Kim, TN, et al. The association between the ratio of visceral fat to thigh muscle area and metabolic syndrome: the Korean Sarcopenic Obesity Study (KSOS). Clin Endocrinol. 2010; 73, 588594.
39. Ong, KK, Ahmed, ML, Emmett, PM, Preece, MA, Dunger, DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. Br Med J. 2000; 320, 967971.
40. Goy, RW, Hoar, RM, Young, WC. Length of gestation in the guinea pig with data on the frequency and time of abortion and stillbirth. Anat Rec. 1957; 128, 747757.
41. Sohlstrom, A, Katsman, A, Kind, KL, et al. Food restriction alters pregnancy-associated changes in IGF and IGFBP in the guinea pig. Am J Physiol. 1998; 274(Pt 1), E410E416.
42. Davis, SR, Mepham, TB, Lock, KL. Relative importance of pre-partum and post-partum factors in the control of milk yield in the guinea-pig. J Dairy Res. 1979; 46, 613621.
43. Mepham, TB, Beck, NFG. Variation in the yield and composition of milk throughout lactation in the guinea pig (Cavia porcellus). Comp Biochem Physiol A Physiol. 1973; 45, 273281.
44. Phillips, DI, Barker, DJP, Hales, CN, Hirst, S, Osmond, C. Thinness at birth and insulin resistance in adult life. Diabetologia. 1994; 37, 150154.
45. Law, CM, Gordon, GS, Shiell, AW, Barker, DJ, Hales, CN. Thinness at birth and glucose tolerance in seven-year-old children. Diabetic Med. 1995; 12, 2429.
46. Rosenberg, A. The IUGR newborn. Semin Perinatol. 2008; 32, 219224.
47. Ravelli, ACJ, Vandermeulen, JHP, Michels, RPJ, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet. 1998; 351, 173177.
48. De Blasio, MJ, Gatford, KL, Robinson, JS, Owens, JA. Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb. Am J Physiol. 2007; 292, 875886.
49. Kelleher, MA, Hirst, JJ, Palliser, HK. Changes in neuroactive steroid concentrations after preterm delivery in the guinea pig. Reprod Sci. 2013; 20, 13651375.
50. Ounsted, M, Sleigh, G. The infant’s self-regulation of food intake and weight gain. Difference in metabolic balance after growth constraint or acceleration in utero. Lancet. 1975; 1, 13931397.
51. Shin, BC, Dai, Y, Thamotharan, M, Gibson, LC, Devaskar, SU. Pre- and postnatal calorie restriction perturbs early hypothalamic neuropeptide and energy balance. J Neurosci Res. 2012; 90, 11691182.
52. Tenovuo, A, Kero, P, Piekkala, P, et al. Growth of 519 small for gestational age infants during the first two years of life. Acta Paediatr Scand. 1987; 76, 636646.
53. Albertsson Wikland, K, Boguszewski, M, Karlberg, J. Children born small-for-gestational age: postnatal growth and hormonal status. Horm Res. 1998; 49(Suppl. 2), 713.
54. Karlberg, J, Albertsson Wikland, K. Growth in full-term small-for-gestational-age infants: from birth to final height. Pediatr Res. 1995; 38, 733739.
55. Hokken-Koelega, AC, De Ridder, MA, Lemmen, RJ, et al. Children born small for gestational age: do they catch up? Pediatr Res. 1995; 38, 267271.
56. Holness, MJ, Sugden, MC. Antecedent protein restriction exacerbates development of impaired insulin action after high-fat feeding. Am J Physiol. 1999; 39, E85E93.
57. Benyshek, DC, Johnston, CS, Martin, JF. Post-natal diet determines insulin resistance in fetally malnourished, low birthweight rats (F1) but diet does not modify the insulin resistance of their offspring (F2). Life Sci. 2004; 74, 30333041.
58. Dobson, CC, Mongillo, DL, Brien, DC, et al. Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring. Nutr Diabetes. 2012; 2, e57.
59. Law, CM, Barker, DJ, Osmond, C, Fall, CH, Simmonds, SJ. Early growth and abdominal fatness in adult life. J Epidemiol Commun Health. 1992; 46, 184186.
60. Rogers, I, the EURO-BLCS Study Group. The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life. Int J Obes Relat Metab Disord. 2003; 27, 755777.
61. Kensara, OA, Wootton, SA, Phillips, DI, et al. Fetal programming of body composition: relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen. Am J Clin Nutr. 2005; 82, 980987.
62. Ravelli, ACJ, van der Meulen, JHP, Osmond, C, Barker, DJP, Bleker, OP. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr. 1999; 70, 811816.


Spontaneous intrauterine growth restriction due to increased litter size in the guinea pig programmes postnatal growth, appetite and adult body composition

  • D. M. Horton (a1) (a2), D. A. Saint (a2), J. A. Owens (a1) (a2), K. L. Kind (a1) (a3) and K. L. Gatford (a1) (a2)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed