Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine growth retardation in rats.
OBJECTIVE
To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1A1 (CYP1A1) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYP1A1 in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats.


METHODS
An IUGR model was produced by passive tobacco smoking from GD7 to parturition (GD21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYP1A1 and P-gp (mdr 1a and mdr 1b) were detected using a reverse transcription polymerase chain reaction and immunohistochemistry.


RESULTS
Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities of superoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYP1A1 mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD21 but not at GD14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta.


CONCLUSIONS
The expression of placental CYP1A1 and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYP1A1 can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism, upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR.
Yan
You-e
YE
Department of Pharmacology, Medical College of Wuhan University, Wuhan 430071, China.
Wang
Hui
H
Feng
Ying-hong
YH
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D019363:Cytochrome P-450 CYP1A1; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C095122:multidrug resistance protein 3