Fetal survivin Fetal survivin concentrations in normal concentrations in normal and complicated and complicated pregnancies at term pregnancies at term Ariadne Malamitsi-Puchner Ariadne Malamitsi-Puchner 1 1 , Maria Boutsikou , Maria Boutsikou 1 1 , Sophia , Sophia Liosi Liosi 1 1 , Dimitrios Gourgiotis , Dimitrios Gourgiotis 2 2 , Venetia-Maria Vraila , Venetia-Maria Vraila 2 2 , , Dimitrios Hassiakos Dimitrios Hassiakos 1 1 , Stavroula Baka , Stavroula Baka 1 1 , Despina D. , Despina D. Briana Briana 1 1 1. 1. Neonatal Division, 2nd Department of Obstetrics and Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece Gynecology, Athens University Medical School, Athens, Greece 2.Research Laboratories, 2nd Department of Pediatrics, Athens 2.Research Laboratories, 2nd Department of Pediatrics, Athens University Medical School, Athens, Greece University Medical School, Athens, Greece
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Fetal survivin Fetal survivin concentrations in normal concentrations in normal
and complicated and complicated pregnancies at termpregnancies at term
1.1. Neonatal Division, 2nd Department of Obstetrics and Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens University Medical School, Athens, GreeceGynecology, Athens University Medical School, Athens, Greece2.Research Laboratories, 2nd Department of Pediatrics, Athens 2.Research Laboratories, 2nd Department of Pediatrics, Athens
University Medical School, Athens, GreeceUniversity Medical School, Athens, Greece
ApoptosisApoptosis
• Programmed cell deathProgrammed cell death• regulates cell proliferation regulates cell proliferation • contributes to tissue and organ contributes to tissue and organ
homeostasis homeostasis • important for the development of normal important for the development of normal
human placenta human placenta
Disturbances in feto-placental Disturbances in feto-placental apoptosis seem to be associated apoptosis seem to be associated with abnormal pregnancy outcomewith abnormal pregnancy outcome
• fetal macrosomia, due to maternal fetal macrosomia, due to maternal diabetes mellitus (DM) diabetes mellitus (DM)
• IUGRIUGR is correlated withis correlated with --increased incidence of apoptosis in IUGR-affected fetal increased incidence of apoptosis in IUGR-affected fetal
membranesmembranes -abnormal -abnormal expression of proteins involved in apoptosis expression of proteins involved in apoptosis
and cell turnover and cell turnover
• Fetal macrosomiaFetal macrosomia is correlated withis correlated with -decreased apoptosis in placental cells-decreased apoptosis in placental cells
SurvivinSurvivin
• 16.5 kD protein16.5 kD protein • member of the inhibitors of apoptosis (IAP) member of the inhibitors of apoptosis (IAP)
familyfamily • prominently expressed in fetal tissues and over-prominently expressed in fetal tissues and over-
expressed in cancer cells expressed in cancer cells • important for normal fetal development important for normal fetal development • plays critical roles in placental cell survival and plays critical roles in placental cell survival and
• Umbilical cord blood Umbilical cord blood concentrations of survivin in concentrations of survivin in IUGR and large-for-gestational-age (LGA-due to IUGR and large-for-gestational-age (LGA-due to gestational DM) cases may differ from gestational DM) cases may differ from respective concentrations in appropriate-for-respective concentrations in appropriate-for-gestational-age (AGA) controls, since the former gestational-age (AGA) controls, since the former are associated with excessive and reduced are associated with excessive and reduced feto-placental apoptosis, respectively. feto-placental apoptosis, respectively.
AIM OF THE STUDYAIM OF THE STUDY
• Investigate cord blood survivin concentrations in IUGR, LGA and AGA pregnancies at birth
• Correlate determined concentrations with gestational age, gender and mode of delivery..
CAUSES OF INTRAUTERINE CAUSES OF INTRAUTERINE GROWTH RESTRICTIONGROWTH RESTRICTION
• Preeclampsia (Preeclampsia ( n=19 )n=19 ) • Hypertensive disease of pregnancy Hypertensive disease of pregnancy (n=16(n=16 ))• Various diseases : Various diseases : severe type I DMsevere type I DM
(( n=2) , iron deficiency anemia (n=4), n=2) , iron deficiency anemia (n=4), hypothyroidismhypothyroidism (n=4)(n=4)
• Determination of plasma survivinDetermination of plasma survivin concentrations by enzyme immunoassayconcentrations by enzyme immunoassay ((Human Total Survivin EIAHuman Total Survivin EIA , , Assay Assay Designs, Designs, 5777 Hines Drive, Ann Arbor, 5777 Hines Drive, Ann Arbor, MI 48108, U.S.AMI 48108, U.S.A ))
Fig. 1.Fig. 1. Cord blood survivin concentrations Cord blood survivin concentrations in AGA, IUGR and LGA pregnanciesin AGA, IUGR and LGA pregnancies ..
LGA IUGRAGA
Su
rviv
in c
once
ntr
atio
ns
(p
g/m
l)
400
300
200
100
0
ResultsResults
• NoNo statistically significant differences in statistically significant differences in cord blood survivin concentrations cord blood survivin concentrations between IUGR, LGA and AGA groups.between IUGR, LGA and AGA groups.
ResultsResults
• In the three groupsIn the three groups• The effect of group (IUGR, LGA, AGA) The effect of group (IUGR, LGA, AGA) (Fig.1)(Fig.1), ,
birthweight, cbirthweight, customized customized centile, gestational age, gender, entile, gestational age, gender, mode of deliverymode of delivery and parity and parity on circulating survivin on circulating survivin
concentrations concentrations was not significantwas not significant • Reference survivin values (median, range): 138.49 Reference survivin values (median, range): 138.49
pg/mL and 71.54 - 349.89 pg/mL, respectivelypg/mL and 71.54 - 349.89 pg/mL, respectively
Conclusions 1Conclusions 1
• Cord blood survivin concentrationsCord blood survivin concentrations in full-term in full-term pregnancies are independent of intrauterine pregnancies are independent of intrauterine growthgrowth
• Cord blood survivin concentrations probably do Cord blood survivin concentrations probably do not reflect the disturbances of feto-placental not reflect the disturbances of feto-placental apoptosis expected in IUGR and fetal apoptosis expected in IUGR and fetal macrosomia, due to gestational DMmacrosomia, due to gestational DM
Conclusions 2Conclusions 2
• PParity, gender and mode of delivery arity, gender and mode of delivery (vaginal or elective cesarean section) do (vaginal or elective cesarean section) do not seem to have any impact on umbilical not seem to have any impact on umbilical cord blood survivin concentrationscord blood survivin concentrations
Conclusions 3Conclusions 3
• Reference values (median) for Reference values (median) for cord blood survivin concentrations cord blood survivin concentrations at term were 138.49 pg/mLat term were 138.49 pg/mL