In-vivo gene transfer to the uterine endometrium.
Therapeutic interventions in reproductive biology have relied largely on steroids and antisteroids which act to regulate gene expression in target tissues. Whilst their use has transformed women's lives, few conceptual advances have been made in contraceptive technology, no means identified to improve human implantation and no new strategies developed for the treatment of benign gynaecology. A novel alternative is direct gene transfer to the organ of interest. As a first step to achieving this goal in the uterus, we used reporter gene constructs to transfect mouse endometrium in vivo and human endometrial epithelial cells in vitro. We injected DNA-liposome complexes into the uterine lumen of mice on day 2 of pseudopregnancy and detected reporter gene activity 2 days later. The liposomes used were a 3:1 (w/w) mixture of 2,3-dioleyloxy-N-[2(sperminecarboxamido) ethyl]-N-N-dimethyl-1-propanaminium trifluoroacetate and dioleoylphosphatidyl ethanolamine. Freshly isolated human endometrial epithelial cells were successfully transfected in vitro with similar DNA-liposome complexes. These data suggest that endometrial gene transfer may be effective in humans. This may lead to the development of new therapeutic agents, including contraceptives, for the improvement of women's health.
Charnock-Jones
D S
DS
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, UK.
Sharkey
A M
AM
Jaggers
D C
DC
Yoo
H J
HJ
Heap
R B
RB
Smith
S K
SK
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage; D004717:Endometrium / Q000201:enzymology*; D004848:Epithelium / Q000201:enzymology; D005260:Female; D018014:Gene Transfer Techniques; D006651:Histocytochemistry; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011555:Pseudopregnancy; D001616:beta-Galactosidase / Q000235:genetics*
D008081:Liposomes; D004247:DNA; D001616:beta-Galactosidase