Abstract
Intrauterine growth restricted (IUGR) infants have increased susceptibility to infection associated with higher risk of illness and death. Dual specificity phosphatase 1 (DUSP1), which is transcribed in the thymus, increases in quantity as T cells mature and differentiate into CD4+ cells. Little is known about how IUGR affects DUSP1 levels and T-cell subpopulations over time. We hypothesized that IUGR would decrease cell count, CD4+ and CD8+ subpopulations of T lymphocytes, and DUSP1 levels in IUGR rat thymus and spleen. Bilateral uterine artery ligation produced IUGR rats. Thymus and spleen were harvested at P0 and P21. Flow cytometry was used to compare CD4+ and CD8+ lymphocyte populations. Real-time RT-PCR and Western blotting were used to determine DUSP1 quantity. IUGR significantly decreased total cell count in P0 and P21 IUGR male and female thymus. IUGR significantly increased CD4+ cells in IUGR P0 males and females, significantly decreased CD4+ cells in P21 female thymus, and significantly altered DUSP1 levels in the IUGR female thymus at P0 and P21, although it is not yet known whether the change in DUSP1 levels is due to a change in the level per cell or to a change in cellular composition of the thymus.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- DUSP1:
-
dual specificity phosphatase 1
- LPS:
-
lipopolysaccharide
- UPI:
-
uteroplacental insufficiency
References
Gortner L, Wauer RR, Stock GJ, Reiter HL, Reiss I, Jorch G, Hentschel R, Hieronimi G 1999 Neonatal outcome in small for gestational age infants: do they really better?. J Perinat Med 27: 484–489
Witlin AG, Sibai BM 1997 Hypertension in pregnancy: current concepts of preeclampsia. Annu Rev Med 48: 115–127
Zhang J, Zeisler J, Hatch MC, Berkowitz G 1997 Epidemiology of pregnancy-induced hypertension. Epidemiol Rev 19: 218–232
Chandra RK 1979 Nutritional deficiency and susceptibility to infection. Bull World Health Organ 57: 167–177
Victora CG, Smith PG, Vaughan JP, Nobre LC, Lombardi C, Teixeira AM, Fuchs SM, Moreira LB, Gigante LP, Barros FC 1988 Influence of birth weight on mortality from infectious diseases: a case-control study. Pediatrics 81: 807–811
Moore SE, Collinson AC, Tamba N′Gom P, Aspinall R, Prentice AM 2006 Early immunological development and mortality from infectious disease in later life. Proc Nutr Soc 65: 311–318
Lira PI, Ashworth A, Morris SS 1996 Low birth weight and morbidity from diarrhea and respiratory infection in northeast Brazil. J Pediatr 128: 497–504
Ashworth A 1998 Effects of intrauterine growth retardation on mortality and morbidity in infants and young children. Eur J Clin Nutr 52: S34–S41
McDade TW, Beck MA, Kuzawa C, Adair LS 2001 Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr 74: 543–548
Moore SE, Jalil F, Ashraf R, Szu SC, Prentice AM, Hanson LA 2004 Birth weight predicts response to vaccination in adults born in an urban slum in Lahore, Pakistan. Am J Clin Nutr 80: 453–459
Cromi A, Ghezzi F, Raffaelli R, Bergamini V, Siesto G, Bolis P 2009 Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obstet Gynecol 33: 421–426
Hartge R, Jenkins DM, Kohler HG 1978 Low thymic weight in small-for-dates babies. Eur J Obstet Gynecol Reprod Biol 8: 153–155
Abbas AK, Lichtman AH, Pillai S 2007 Cellular and Molecular Immunology. Saunders Elsevier, Philadelphia, pp 114–118
Ferguson AC 1978 Prolonged impairment of cellular immunity in children with intrauterine growth retardation. J Pediatr 93: 52–56
Thilaganathan B, Plachouras N, Makrydimas G, Nicolaides KH 1993 Fetal immunodeficiency: a consequence of placental insufficiency. Br J Obstet Gynaecol 100: 1000–1004
Mustelin T, Alonso A, Bottini N, Huynh H, Rahmouni S, Nika K, Louis-dit-Sully C, Tautz L, Togo SH, Bruckner S, Mena-Duran AV, al-Khouri AM 2004 Protein tyrosine phosphatases in T cell physiology. Mol Immunol 41: 687–700
Tanzola MB, Kersh GJ 2006 The dual specificity phosphatase transcriptome of the murine thymus. Mol Immunol 43: 754–762
Liu Y, Shepherd EG, Nelin LD 2007 MAPK phosphatases—regulating the immune response. Nat Rev Immunol 7: 202–212
Hammer M, Mages J, Dietrich H, Servatius A, Howells N, Cato AC, Lang R 2006 Dual specificty phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock. J Exp Med 203: 15–20
Ogata ES, Swanson SL, Collins JW, Finley SL 1990 Intrauterine growth retardation: altered hepatic energy and redox states in the fetal rat. Pediatr Res 27: 56–63
Baserga M, Hale MA, Ke X, Wang ZM, Yu X, Callaway CW, McKnight RA, Lane RH 2006 Uteroplacental insufficiency increases p53 phosphorylation without triggering the p53-MDM2 functional circuit response in the IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol 291: R412–R418
World Medical Association American Physiological Society 2002 Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol 283: R281–R283
Klein J, Hořejšà V 1997 Immunology. Blackwell Science, Oxford, pp 32–36
Vicente A, Varas A, Acedón RS, Jiménez E, Muñoz JJ, Zapata AG 1998 Appearance and maturation of T-cell subsets during rat thymus ontogeny. Dev Immunol 5: 319–331
Götz AA, Wittlinger S, Stefanski V 2007 Maternal social stress during pregnancy alters immune function and immune cell numbers in adult male Long-Evans rat offspring during stressful life-events. J Neuroimmunol 185: 95–102
Llorente E, Brito ML, Machado P, González MC 2002 Effect of prenatal stress on the hormonal response to acute and chronic stress and on immune parameters in the offspring. J Physiol Biochem 58: 143–149
Klein SL, Rager DR 1995 Prenatal stress alters immune function in the offspring of rats. Dev Psychobiol 28: 321–336
Hashimoto M, Watanabe T, Fujioka T, Tan N, Yamashita H, Nakamura S 2001 Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress. Physiol Behav 73: 125–132
Sobrian SK, Vaughn VT, Ashe WK, Markovic B, Djuric V, Jankovic BD 1997 Gestational exposure to loud noise alters the development and postnatal responsiveness of humoral and cellular components of the immune system in offspring. Environ Res 73: 227–241
Kay G, Tarcic N, Poltyrev T, Weinstock M 1998 Prenatal stress depresses immune function in rats. Physiol Behav 63: 397–402
Götz AA, Stefanski V 2007 Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behaviour in adult male rat offspring. Physiol Behav 90: 108–115
Ogata ES, Bussey ME, LaBarbera A, Finley S 1985 Altered growth, hypoglycemia, hypoalaninemia, and ketonemia in the young rat: postnatal consequences of intrauterine growth retardation. Pediatr Res 19: 32–37
Economides DL, Nicolaides KH 1989 Blood glucose and oxygen tension levels in small-for-gestational-age fetuses. Am J Obstet Gynecol 160: 385–389
Nicolaides KH, Economides DL, Soothill PW 1989 Blood gases, pH, and lactate in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 161: 996–1001
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the Children's Health Research Center (CHRC).
Rights and permissions
About this article
Cite this article
Contreras, Y., Yu, X., Hale, M. et al. Intrauterine Growth Restriction Alters T-Lymphocyte Cell Number and Dual Specificity Phosphatase 1 Levels in the Thymus of Newborn and Juvenile Rats. Pediatr Res 70, 123–129 (2011). https://doi.org/10.1203/PDR.0b013e31821f6e75
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31821f6e75
This article is cited by
-
Dentate granule progenitor cell properties are rapidly altered soon after birth
Brain Structure and Function (2018)
-
Effects of intrauterine growth retardation and Bacillus subtilis PB6 supplementation on growth performance, intestinal development and immune function of piglets during the suckling period
European Journal of Nutrition (2017)
-
Increased Fetal Thymocytes Apoptosis Contributes to Prenatal Nicotine Exposure-induced Th1/Th2 Imbalance in Male Offspring Mice
Scientific Reports (2016)
-
Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation
Cell Stress and Chaperones (2012)


