title: Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector.
abstract: The uterus is obviously critical in implantation, development of the fetus and parturition. Endometrial cancer derived from endometrial epithelium is one of the common malignancies in the female reproductive tract. In order to clarify the local mechanisms of reproductive physiology and establish a non-systemic therapeutic strategy for reproductive failure as well as for endometrial cancer, we applied haemagglutinating virus of Japan envelope (HVJ-E) vector to in-vivo gene transfer into the uterine cavity of IVCS mice. Injection of HVJ-E vector into mouse uterine cavity on day 1.5 post coitum (p.c.) introduced a reporter gene approximately 120-fold more efficiently than introduction using the cationic liposome method. The expression of the introduced gene continued for at least 3 days. The plasmid vector was localized in the endometrial epithelium, whereas oligo deoxynucleotides were distributed throughout the epithelium, stromal cells and myometrium. HVJ-E vector did not affect the pregnancy rate, course of pregnancy, litter size, fetal growth in utero or parturition, and did not transfect the exogenous gene to the fetus. These results indicate that gene transfer into the uterus using HVJ-E vector is highly efficient and safe during pregnancy, and results in a well controlled distribution of the exogenous DNA. We believe that this procedure should be widely applicable for investigations of reproductive physiology as well as for methods of local gene therapy in the uterus.
authors.affiliation: Division of Obstetrics and Gynecology, Department of Specific Organ Regulation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ikegami
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogita
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Koyama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shimoya
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsujie
authors.forename: Masayasu
authors.initials: M
authors.lastname: Koyama
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Murata
mesh_terms: D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D029082:Sendai virus / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014599:Uterus / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D008156:Luciferases; D001616:beta-Galactosidase