Effects of Zidovudine (AZT) and dideoxyinosine (ddI) on human trophoblast cells

The anti-MN agents AZT (zidovudine) and ddI (dideoxyinosine) are being used clinically during pregnancy. The toxicity of these agents to the fetus and placenta remains a concern because few human pregnancy exposure data are a vailable, and pregnant rodent studies with AZT indicate increased embryonic resorptions and developmental arrest. The current study used a human chori ocarcinoma cell line (JAr), which exhibits many characteristics of the earl y placenta, to assess the effects of a single 24 h exposure of 7.6 or 0.076 mM AZT, and the effects of a single 24 h exposure of 7.6 or 0.076 mM ddI u pon cell proliferation and hormone production of human chorionic gonadotrop in (hCG), estradiol (E-2), and progesterone (P-4). The higher concentration of AZT and ddI produced significant (P < 0.025) reductions in cell numbers and growth rate while producing significant increases in hormone productio n (hCG, E-2, and P-4). The lower concentration of AZT and ddI produced sign ificant increases in E-2 production, but no changes in cell numbers, hCG, o r P-4. Because placental cells require androgen precursor for E-2 synthesis , exogenous androstenedione was added to confirm observations of increased estradiol synthesis after AZT or ddI exposure. These results demonstrate th at single 24 h high dose exposures of AZT or ddI produce significant inhibi tion of eel proliferation and alterations in hormone production in this par adigm of human placental cells. (C) 1999 Elsevier Science Inc. All rights r eserved.