title: Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.
abstract: Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.
authors.affiliation: Department of Maternal and Child Health Care, Centers for Disease Control and Prevention of Suzhou Industrial Park, Suzhou 215021, China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: S C
authors.initials: SC
authors.lastname: Qu
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Feng
authors.forename: X L
authors.initials: XL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005312:Fetal Blood; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D011284:Pregnenolone / Q000097:blood; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050497:Stillbirth; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000633:toxicity
chemical_list: D018765:Dopamine Uptake Inhibitors; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C580807:Stard3nl protein, rat; D050656:Transcription Factor AP-2; D014662:Vasoconstrictor Agents; D011374:Progesterone; D011284:Pregnenolone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003042:Cocaine