Transduction patterns and efficiencies in rabbit uterine tissues after intraluminal uterine adenovirus administration vary with the reproductive cycle.
BACKGROUND
The options for destroying the full thickness of endometrium are very limited, relying mainly on surgical endometrial ablation. A nonsurgical, safe method would benefit many women in clinical settings. This study was undertaken to investigate the potential of gene therapy to transfect and destroy endometriun at different stages of the reproductive cycle in rabbits.


METHODS
We used adenoviruses carrying the LacZ (AdvLacZ) marker gene, indicating the transfection efficiency, and adenoviruses carrying thymidine kinase (AdvTK) followed by intravenous ganciclovir therapy as a potential treatment for excess endometrial growth. Ganciclovir was given intravenously after AdvTK treatment. Adenoviruses were injected intraluminally into the uterus of nonpregnant, pseudopregnant, and pregnant New Zealand White rabbits (n=25).


RESULTS
After AdvLacZ gene transfer into the uterus of intact rabbits, transduced cells were observed in uterine muscle and endometrial stroma. In pseudopregnant and pregnant rabbits the endometrium was proliferative and transduction was restricted to endometrial epithelium. However, no treatment effect was observed after AdvTK gene therapy although the transduction with AdvLacZ was clearly detectable.


CONCLUSIONS
It is concluded that the transduction pattern of uterine tissues varies significantly with the reproductive cycle. Secondly, although the transduction efficiency was relatively high in the endometrial epithelium, the effect of the AdvTK and ganciclovir treatment was poor and not sufficient for clinical applications.
Laurema
Anniina
A
A.I. Virtanen Institute, Kuopio, Finland.
Lumme
Satu
S
Heinonen
Suvi E
SE
Heinonen
Seppo
S
Ylä-Herttuala
Seppo
S
D000256:Adenoviridae / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis; D004717:Endometrium / Q000201:enzymology / Q000473:pathology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007763:Lac Operon / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011817:Rabbits; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods*; D014162:Transfection / Q000379:methods; D014599:Uterus / Q000378:metabolism / Q000473:pathology
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir