This study investigated transforming growth factor beta 1 (TGF-β1) concentrations in umbilical cord blood from pregnancies complicated by intrauterine growth restriction (IUGR) compared to appropriate-for-gestational-age (AGA) controls. The study found no significant differences in TGF-β1 concentrations between the IUGR and AGA groups. Higher TGF-β1 concentrations were associated with vaginal delivery and lower infant growth percentiles in the IUGR group. The results suggest TGF-β1 may be related to fetal growth but not directly involved in pathophysiological processes leading to IUGR.
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Tgf β1 europaediatrics 2009
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. 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. 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. 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
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. 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. 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. Gestation Related Optimal
Weight (GROW) computergenerated programme
www.gestation.net
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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. Results (1)
• No statistically significant differences in
cord blood TGF -β1 concentrations
between IUGR and AGA groups .
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. Results (3)
• In the AGA group
• Cord blood TGF-β1 concentrations were
higher in primigravidas
17. Results (4)
• In the IUGR group
• Cord blood TGF- β1 concentrations
negatively correlated with infant’s
customized centiles
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. 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. Conclusions (3)
• Stress associated with vaginal delivery
may account for the higher TGF-β1
concentrations in the latter.
Hinweis der Redaktion
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