Increased production of tumor necrosis factor-alpha TNF-alpha by IUGR human placentae.
OBJECTIVE
To evaluate the effect of pathological placental conditions such as intrauterine growth restriction (IUGR) or exposure to angiotensin II (AII) on TNF-alpha secretion in the vasculature of isolated human placental cotyledons.


METHODS
Isolated placental cotyledons from 10 normal and four intrauterine growth restricted fetuses were dually perfused. Perfusate samples from the fetal circulation were collected every 30 min during 120 min. TNF-alpha levels in the fetal-placental perfusate were evaluated using specific commercial ELISA kits. In three additional normal placentae, bolus injections of angiotensin II (10(-9)-10(-4) mol/l) were given into the fetal-placental circulation and perfusate samples were collected. Statistical significance of difference TNF-alpha levels between different conditions was determined by analysis of variance (ANOVA) and paired t-test.


RESULTS
TNF-alpha levels were significantly higher in the perfusate of IUGR placentae as compared with normal placentae after 120 min of perfusion (mean 410+/-121 vs. 39+/-14 pg/ml, P=0.005). There was a significant dose-dependent increase in TNF-alpha levels in the placental perfusate after a bolus injection of AII 66 pg/ml with AII 10(-9) mol/l vs. 97 pg/ml with AII 10(-5) mol/l (P=0.004), respectively.


CONCLUSIONS
Placental pathology related to condition IUGR might induce the secretion of proinflammatory cytokines such as TNF-alpha, which may enhance the vasoconstriction of the fetal placental vascular bed.
Holcberg
G
G
Division of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 151, 84101, Beer Sheva, Israel. holcberg@bgumail.bgu.ac.il
Huleihel
M
M
Sapir
O
O
Katz
M
M
Tsadkin
M
M
Furman
B
B
Mazor
M
M
Myatt
L
L
D000804:Angiotensin II / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D021041:Placental Circulation / Q000187:drug effects; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II