Effect of ethanol on thromboxane and prostacyclin production in the human placenta.
Fetal alcohol syndrome (FAS) is frequently associated with intrauterine growth retardation (IUGR). One cause of ethanol-induced IUGR is thought to be related to increased pressor activity in the human placenta, resulting in decreased oxygenation and nutrient transport to the fetus. Thus, we have investigated the effect of ethanol on paracrine substances, such as thromboxane and prostacyclin, that act as vasoregulators within the intrauterine tissues. In these studies we have utilized the perfused single human cotyledon system to study the effect of ethanol on placental prostanoid production. We assessed the effect of longer (240 min) and more acute (60 min) exposure to ethanol on release of thromboxane B(2) (TxB(2)) and 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) at the maternal and fetal sides of the placenta. Thromboxane was increased by both longer and shorter ethanol exposure, especially on the fetal side of the placenta. Prostacyclin was essentially unchanged with exposure to ethanol. The thromboxane:prostacyclin ratio also tended to increase with both 60- and 240-min ethanol exposure, but a statistically significant increase was seen only at a few time points. In the 60-min ethanol exposure, an increase in thromboxane was observed both during and following exposure to ethanol. The increase in the thromboxane milieu observed with ethanol exposure may lead, at least in part, to the IUGR which is frequently associated with FAS. Prevention of this effect of ethanol on thromboxane production might be a beneficial intervention for FAS.
Siler-Khodr
T M
TM
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, Room 416E, 7703 Floyd Curl Drive, San Antonio, TX 78284, USA. silerkhodr@uthscsa.edu
Yang
Y
Y
Grayson
M H
MH
Henderson
G I
GI
Lee
M
M
Schenker
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D013929:Thromboxane B2 / Q000096:biosynthesis*
D000431:Ethanol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha