Tgf β1 europaediatrics 2009


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  • The tgfbmrana is preferentially expressed in crypt rether than villous ,proliferation is stimulated by alpha and switched off by b1
    Most common isoform
    mRNA for TGF/3 and immunoreactive TGFb have been demonstrated in human placenta throughout pregnancy (16). In addition, receptors have been detected for TGFPbin the placenta (17,
  • The tgf-bs have diverse range of biological effects and affect almost every cell in the body
    Stimulare extracellular matrix production,prevent ecm production,inflammmatory cells
    TGF-B de®ciency resulted in severe pathology leading to deathat about 20 days of age associated with dysfunction of the immune and in¯ammatory system, indicating its essential role as a potent regulator of the immune and in¯ammatory system.
  • Tolernce implantation of embryo and gestation//
    Regulation of the local maternal immune response may be necessary to prevent immune rejection of the fetus. TGF/3 is a multifunctional peptide with potent immunosuppressive activities, including inhibition of interleukin-l/3 (IL-l/3)-induced lymphocyte proliferation, lymphokine-activated killer cell activity, cytotoxic T-cell activity,natural killer cell activity, and macrophage cytotoxicity TGFP also inhibits many of the immunostimulatory properties of IL-lp (22).
    The researchers suggested that the increase in decidual IL-l@ and HLA-DRLU during pregnancy may be involved in maternal recognition of the fetal allograft and that TGF/3 production may regulatethe local maternal immune response and prevent rejection of the fetus.
    nhibit enterocyte proliferation + induce terminal differentiation+repair of mucosal epithelium after injury+epithelial restitution…INHIBIT PROLIFERATION
  • Kauma et al. (22) found higher levels of mRNA for TGFPl in decidualized gestational endometrium compared to proliferative (5-fold less) or secretory endometrium (2.5-fold less). This could indicate that the presence of trophoblast and/or the hormonal milieu of pregnancy resulted in an induction of mRNA for TGFPl.
    An additional reported function of TGFP is one of immunosuppression.
  • Tgfb1 lower in iugr, positive correlation with birth weight(ostlund)
  • 5th customized centile
  • The Gestation Related Optimal Weight computer-generated program was used to calculate the customized centile for each pregnancy taking into consideration significant determinants of birth weight, such as maternal height and booking weight, ethnic group, parity, gestational age and gender
  • >10 cigarettes perday during pregnancy
  • Plasma preparation platelet –poor plasma
  • B1 increased in preeclampsia
    Conflict in bibliography =elevated and no difference
    Ostlund IUGR=decreased in IUGR but!!! Measured in serum and isolated IUGR NOT prreclampsia
  • Maternal system inflammatory status!!!!=conflict in bibliography
  • Tgf β1 europaediatrics 2009

    1. 1. CORD BLOOD TGF- β 1 CONCENTRATIONS IN INTRAUTERINE GROWTH RESTRICTED PREGNANCIES AT TERM Sofia Liosi 1 , Despina D. Briana 1 , Stavroula Baka 1 , Dimitrios Gourgiotis 2 , Maria Boutsikou 1 , Lamprini Stamati 2 , Dimitrios Hassiakos 1 , Ariadne Malamitsi-Puchner 1 . 1.Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece 2.Research Laboratories, 2nd Department of Pediatrics, Athens University Medical School, Athens, Greece
    2. 2. TGF – β1 • A member of the transforming growth factor beta (TGF-β) family • Three closely related isoforms TGF- β1, TGF-β2, and TGF-β3
    3. 3. TGF-β1 • inhibition of cell growth and transformation • suppression of immune response • promotion of inflammation • a critical regulator of trophoblast invasion and fetal growth.
    4. 4. Intrauterine growth restriction-IUGR • Failure of the fetus to achieve his/her intrinsic growth potential • Consequence of anatomical and/or functional disorders and diseases in the feto-placental-maternal unit • Results to increased morbidity and mortality in intra- and extrauterine life
    5. 5. IUGR • abnormal trophoblast invasion • uteroplacental vascular insufficiency • impaired fetal growth
    6. 6. HYPOTHESIS • Umbilical cord blood concentrations of TGF -β1 in IUGR cases may differ from respective concentrations in appropriatefor-gestational-age (AGA) controls, due to uteroplacental vascular insufficiency
    7. 7. AIM • Investigate cord blood TGF -β1 concentrations in IUGR and AGA pregnancies at birth • Correlate determined concentrations with gestational age, gender and mode of delivery.
    8. 8. SUBJECTS • 160 healthy, singleton full-term pregnancies - 1 10 AGA (placental weight: 480-621 g) - 50 asymmetric IUGR ( placental weight 230- 400g) • Apgar scores: > 8 in 1 st and 5 th minute
    9. 9. Gestation Related Optimal Weight (GROW) computergenerated programme d 6 5 P p E x S c l M n k o G ) h g w r i B y D e a m t s u C ( b : = W
    10. 10. DEMOGRAPHIC DATA • • • • • • IUGR Gestational age (weeks) 38 .36 ±1 .27 * BW (g) 25 07 ± 264.5 * BW centile 3 .0 (0-5) Gender (male/female) 21/29 Mode of delivery (VD/ECS)** 22/28 Parity (1st /other) 31 / 19 * values are mean ± SD **VD: vaginal delivery/ ECS: elective cesarian section AGA 3 8.98 ± 1.07 * 3 310 ± 310.5* 44.5 (20-99) 66/44 77/33 76/34
    11. 11. CAUSES OF IUGR • Preeclampsia ( n=6 ) • Pregnancy induced hypertension (n=5 ) • Various diseases : severe type I DM • ( n=5),iron deficiency anemia (n=3), hypothyroidism (n=7) Maternal smoking ( n=24 )
    12. 12. Methods • • • Blood collected from: Doubly-clamped umbilical cords (m ixed arteriovenous blood ) – reflecting fetal state Determination of plasma TGF -β1 concentrations by enzyme immunoassay ( Human TGF- β 1 ELISA, R&D OX, UK) Statistical analysis (non-parametric tests)
    13. 13. TGFB1 CONCENTRATIONS (pg/ml) Fig. 1 Box and whiskers plots of the concentrations of TGF β1 UC from AGA and IUGR cases 30000 20000 10000 0 AGA GROUP (N=110) IUGR GROUP (N=50)
    14. 14. Results (1) • No statistically significant differences in cord blood TGF -β1 concentrations between IUGR and AGA groups .
    15. 15. Results (2) • In a combined group • Cord blood TGF -β1 concentrations were significantly elevated in cases of vaginal delivery • The effect of gender, parity and maternal age on cord blood TGF-β1 concentrations was not significant.
    16. 16. Results (3) • In the AGA group • Cord blood TGF-β1 concentrations were higher in primigravidas
    17. 17. Results (4) • In the IUGR group • Cord blood TGF- β1 concentrations negatively correlated with infant’s customized centiles
    18. 18. Conclusions (1) • Lack of differences in cord blood TGF- β 1 • concentrations at term between IUGR and AGA groups possibly suggests that TGF- β 1 may not be directly involved in the pathophysiological processes resulting in IUGR Gender, parity and maternal age do not seem to have any impact on umbilical cord blood TGF- β 1 concentrations
    19. 19. Conclusions (2) • TGF-β1 may be related to fetal growth, as indicated by the higher cord blood TGF-β1 concentrations in primigravidas and their negative correlation with infants’ customized centiles in the IUGR group
    20. 20. Conclusions (3) • Stress associated with vaginal delivery may account for the higher TGF-β1 concentrations in the latter.