Effect of zidovudine on human placental trophoblast and Hofbauer cell functions.
We have optimized a procedure to isolate placental trophoblasts and Hofbauer cells simultaneously in a quantity sufficient for short-term cultures and then used these placental cells to investigate the effects of zidovudine (ZDV) on trophoblast and Hofbauer cell functions. Of more than 10 term placentas tested, ZDV inhibits DNA synthesis of trophoblasts in a concentration-dependent manner with half the maximal inhibitory concentration (IC50) of 9.88 +/- 1.35 microM. Of the hormones evaluated, production of progesterone by trophoblasts is most sensitive to ZDV (IC50 = 3.65 +/- 0.29 microM). The inhibitory effect of ZDV on the secretion of placental lactogen and choriogonadotropin by the trophoblasts was detected only at a much higher concentration (> or = 60 microM). ZDV does not affect trophoblast or Hofbauer cell protein synthesis. Collectively, our results indicate that at clinically relevant concentrations (< or = 10 microM), ZDV significantly inhibits both the DNA synthesis of placental trophoblasts and their production of progesterone, while having a minimal effect on protein synthesis of both types of placental cells.
Bui
T
T
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle.
Bark
D
D
Perkins
M
M
Vu
H
H
Unadkat
J D
JD
Ho
R J
RJ
D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D011388:Prolactin / Q000096:biosynthesis; D014176:Protein Biosynthesis; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*
D006063:Chorionic Gonadotropin; D015215:Zidovudine; D011374:Progesterone; D011388:Prolactin