Transplacental antiretroviral therapy with 9-(2-phosphonylmethoxyethyl)adenine is embryotoxic in transgenic mice.
Transgenic Mov-14 mice, which carry the provirus of Moloney murine leukemia virus (Mo-MuLV) in the germ line and begin to produce infectious virus on embryonic day 14, were used to evaluate the ability of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) to cross the placenta and protect embryos from viremia. We have used the Mov-14 model previously to demonstrate the antiviral efficacy and lack of teratogenicity of transplacental therapy with 3'-azido-3'-deoxythymidine (zidovudine, ZDV). PMEA was administered to pregnant females by daily intraperitoneal injection or by osmotic pump. In contrast to ZDV, PMEA was either noneffective in preventing viremia in the offspring or embryotoxic, depending on the dose. The specific toxic effects seen were resorption of pregnancy, low birth weight, and neonatal death. Histopathological analysis of neonatal mice exposed to PMEA showed severe lymphoid depletion of the thymus. We conclude that PMEA therapy is contraindicated for use during pregnancy.
Lee
J S
JS
Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Boston, MA 02115.
Mullaney
S
S
Bronson
R
R
Sharpe
A H
AH
Jaenisch
R
R
Balzarini
J
J
De Clercq
E
E
Ruprecht
R M
RM
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption; D008098:Litter Size / Q000187:drug effects*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics*; D063065:Organophosphonates; D011247:Pregnancy; D014766:Viremia / Q000517:prevention & control*; D015215:Zidovudine / Q000627:therapeutic use / Q000633:toxicity*
D000998:Antiviral Agents; D063065:Organophosphonates; D015215:Zidovudine; C053001:adefovir; D000225:Adenine