Associate Professor Tetsuo Maruyama of Keio University and Tomoka Takao (Assistant Professor of Okayama University) are collaborating with Professor Moritoshi Sato of the University of Tokyo to combine blue light irradiation with a blue LED (blue light emitting diode) and genome editing. We succeeded in pinpointing the pregnancy (implantation) of mice.
Advances in assisted reproductive technology (ART) such as in vitro fertilization have dramatically improved the results of infertility treatment, but there is still no effective treatment for infertility due to implantation disorders, and the pregnancy rate and production rate of ART have peaked in recent years. is.Implantation that occurs in the womb is difficult to approach, and the mechanism is not fully understood.
Implantation is a phenomenon in which a fertilized egg (embryo) adheres to the uterus and invades the mother's body. Both the embryo and the uterus change from moment to moment, and various biological substances cooperate with each other to support the implantation phenomenon.In this study, we targeted leukemia inhibitory factor (LIF), which is essential for implantation, among these substances for optogenetic manipulation.
First, the gene for photoactivated CRISPR / Cas9 (optical Cas9), which exerts a genome editing (gene modification) function only when irradiated with blue light, is introduced into female mice mated with male mice.When the female mouse was irradiated with blue light, the genome editing of light Cas9 disrupted the LIF gene in the uterus and lowered the LIF protein, so that implantation did not occur and the mouse did not become pregnant.This mouse does not affect LIF unless exposed to blue light, and normally implants and becomes pregnant.Furthermore, when a new LIF protein was administered to the uterus of an infertile mouse whose LIF was lowered by blue light irradiation, implantation occurred almost as before and the mouse became pregnant.
This achievement presents a new research and analysis method for implantation phenomena, and also presents new forms of reproductive treatment such as treatment of infertility such as implantation failure, contraception by implantation block, or fetal treatment in utero. It is expected to lead to the development of.
Paper information:[Proceedings of the National Academy of Sciences] Optogenetic regulation of embryo implantation in mice using photoactivatable CRISPR / Cas9
