November 4, 2020
Keio University School of Medicine
Associate Professor Tetsuo Maruyama and Research Associate Chika Takao (Assistant Professor, Okayama University) of the Department of Obstetrics and Gynecology (Obstetrics), Keio University School of Medicine, in a joint research project with Professor Moritoshi Sato of the University of Tokyo, have succeeded in precisely regulating pregnancy (implantation) in mice by combining genome editing with blue light irradiation from a blue LED.
Pregnancy begins with a phenomenon called implantation, where the fertilized egg (embryo) adheres to the uterine lining and invades the maternal body. During implantation, both the embryo and the uterus undergo constant changes. Within the uterus, various biomolecules work in concert to support this dynamic phenomenon of implantation. Among these substances, we targeted leukemia inhibitory factor (LIF), which is essential for implantation, for optogenetic manipulation. First, we introduced the gene for a photoactivatable CRISPR/Cas9 (photo-Cas9), which exerts its genome-editing function only when irradiated with blue light, into female mice that had been mated with male mice. When these female mice were irradiated with blue light, the photo-Cas9 genome editing disrupted the LIF gene in the uterus, leading to a decrease in LIF protein. As a result, implantation did not occur, and the mice did not become pregnant. Without blue light irradiation, these mice experience normal implantation and pregnancy, as LIF is not affected. Furthermore, when LIF protein was newly administered to the uterus of infertile mice with reduced LIF due to blue light irradiation, implantation was almost fully restored, and they became pregnant.
Research and treatment of the ever-changing phenomena of implantation and pregnancy require technologies that can analyze and control them with spatiotemporal precision. In this study, we succeeded in controlling implantation and pregnancy in mice by altering the function of biomolecules in the uterus by applying light at a targeted location and time. These findings not only present a new research and analysis method for the phenomenon of implantation but are also expected to lead to the development of new forms of reproductive therapies, such as treatment for infertility due to implantation failure, contraception by blocking implantation, or in utero fetal therapy.
The results of this research were published in the online edition of "Proceedings of the National Academy of Sciences" on November 2, 2020 (US Eastern Time).
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