Immunocompetent cells, NK cells, cytokines, infertility, miscarriage

Obstetrics and Gynecology, Reproduction

In recent years, the trend towards later marriage and later childbirth has led to an increase in the number of people suffering from infertility, and measures to combat this problem are urgently needed. On the other hand, NK cells present in peripheral blood and endometrium are thought to play an important role in the establishment and maintenance of pregnancy, but the details are not clear. NK cells have two major functions: cytotoxicity and cytokine production. NKp46, one of the Natural Cytotoxicity Receptors (NCR) expressed on the surface of NK cells, is thought to be involved in both of these functions, and it is known that its expression is abnormal in reproductive disorders such as recurrent pregnancy loss and implantation failure.
The purpose of this study is to elucidate the division of roles and expression of functions of NK cells in reproduction, and to clarify the involvement of NK cells in the establishment and maintenance of pregnancy, and the involvement of NK cells in recurrent pregnancy loss and implantation failure, and how to control them. This study is of great significance as it will lead to the resolution of the above issues, and is expected to be useful in determining treatment policies and developing treatments for infertility.

• Original research seed concept: The immune system, especially NK cell function sharing and functional expression, are important in the establishment and maintenance of pregnancy.
• There are no tests or treatments that can determine the treatment plan for infertility or miscarriage by stimulating the endometrium with semen.

• We have a wealth of data and testing know-how that demonstrates the usefulness of our unique infertility and miscarriage testing method using NK cells (surface markers, cytokine production).
• In addition, there are many proven results that show its usefulness in determining actual treatment plans.

In recent years, the trend towards later marriage and later childbirth has led to issues such as infertility and miscarriage, making measures to combat these problems an urgent task.
This research seed may lead to a better understanding of the pathology of infertility and miscarriage, and even to the establishment of new testing and treatment methods.

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1. Taima A, Fukui A, Yamaya A, Yokota M, Fukuhara R, Yokoyama Y: A semen-based stimulation method to analyze cytokine production by uterine CD56(bright) natural killer cells in women with recurrent pregnancy loss. J Reprod Immunol 2020;142:103206.
2. Mai C, Fukui A, Takeyama R, Yamamoto M, Saeki S, Yamaya A, Kato T, Ukita Y, Wakimoto Y, Shibahara H: NK cells that differ in expression of NKp46 might play different roles in endometrium. J Reprod Immunol 2021;147:103367.
3. Takeyama R, Fukui A, Mai C, Yamamoto M, Saeki S, Yamaya A, Shibahara H: Co-expression of NKp46 with activating or inhibitory receptors on, and cytokine production by, uterine endometrial NK cells in recurrent pregnancy loss. J Reprod Immunol 2021;145:103324
4. Yamamoto M, Fukui A, Mai C, Saeki S, Takayama R, Wakimoto Y, Yamaya A, Kwak-Kim J, Shibahara H: Evaluation of NKp46 expression and cytokine production of decidual NK cells in women with recurrent pregnancy loss. Reprod Med Biol 2022;21:e12478.