Diabetes-induced fetal growth retardation is associated with suppression of NF-kappaB activity in embryos.
BACKGROUND
Mechanisms underlying diabetes-induced fetal growth retardation remain largely undefined. Two events such as the persistent activation of apoptosis or suppression of cell proliferation in embryos might directly result in fetal growth retardation. Evidence implicating the transcription factor NF-kappaB in the regulation of the physiological and teratogen-induced apoptosis as well as cell proliferation suggests that it may be a component of mechanisms underlying this pathology. To address this issue, this study was designed to test: 1) whether diabetes-induced fetal growth retardation is preceded by the modulation of NF-kappaB activity in embryos at the late stage of organogenesis and 2) whether apoptosis is altered in these embryos.


METHODS
The embryos and placentas of streptozotocin-induced diabetic mice collected on days 13 and 15 of pregnancy were used to evaluate the expression of NF-kappaB, IkappaBalpha and phosphorylated (p)-IkappaBalpha proteins by Western blot analysis and NF-kappaB DNA binding by an ELISA-based method. The detection of apoptotic cells was performed by the TUNEL assay and the expression of a proapoptotic protein Bax was evaluated by the Western blot.


RESULTS
The embryos of diabetic mice were significantly growth retarded, whereas the placental weight did not differ in diabetic or control females. Levels of NF-kappaB and p-IkappaBalpha proteins as well as the amount of NF-kappaB DNA binding was lower in embryos of diabetic mice as compared to those in controls. However, neither excessive apoptosis nor an increased Bax expression was found in growth-retarded embryos and their placentas.


CONCLUSIONS
The study herein revealed that diabetes-induced fetal growth retardation is associated with the suppression of NF-kappaB activity in embryos, which seems to be realized at the level of IkappaB degradation.
Mammon
Keren
K
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Keshet
Rotem
R
Savion
Shoshana
S
Pekar
Olga
O
Zaslavsky
Zeev
Z
Fein
Amos
A
Toder
Vladimir
V
Torchinsky
Arkady
A