Conditional system of controllable fertility through targeting implantation

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The purpose of this study was to develop a conditional animal model whose fertility could be controlled through internal and external modification of implantation-associated genes. We employed two different approaches : 1) generation of genetically engineered mice (OPG-creTG) whose endometrial genes could be modulated spatially and temporally by doxycycline (DOX)- driven Cre-loxP system, and 2) introduction of DNA harboring the gene of interest into the uterine cavity by ultrasound exposure in the presence of microbubbles (sonoporation). Cre recombinase was successfully induced in the presence of DOX in the uterine tissue excised from OPG-creTG. Furthermore, OPG-creTG were crossed with the Rosa26R reporter mouse, which possessed a floxed repressor element associated with a lacZ transgene, in order to validate the functional efficacy of the conditionally expressed Cre. The results demonstrated that excision of the floxed element could be achieved specifically and conditionally in the endometrium, in particular, endometrial glandular cells; however, the conditions for maximal and reproducible induction of Cre remained to be improved and optimized. We found that genes could be introduced into the endometrium, in particular, luminal and glandular epithelium, much more efficiently by sonoporation than by liposome-based transfection. Thus, our animal model may be applicable as a conditional system of controllable fertility through targeting implantation, i.e., interaction between embryo and surface epithelium of the endometrium.