Testis, germ cells, Leydig cells, Sertoli cells, sepsis

Emergency and Intensive Care Medicine

Post-intensive care syndrome can cause physical disorders such as respiratory disorders, neuromuscular disorders, and motor dysfunction, as well as cognitive and mental disorders after intensive care in the ICU, but its impact on reproductive and gonadal function after treatment for severe illness is unknown. Focusing on sepsis, a severe infection, approximately 20% of male sepsis patients are aged 18 to 45 years, including those of reproductive age, and investigating reproductive and gonadal function after severe infection is considered important from the perspective of QOL after recovery.
We found that endogenous IL-18 induces apoptosis of testicular germ cells during acute inflammation caused by endotoxin, but inhibits it during the recovery period after acute inflammation. We also found that high concentrations of LPS and IL-18 promote apoptosis of Leydig cells, which are male hormone-producing cells, but do not induce apoptosis of Sertoli cells (involved in spermatogenesis and differentiation, forming the blood-testis barrier), demonstrating that the cells that compose the testis have different sensitivities to exogenous and endogenous harmful substances.
This study is believed to be the beginning of a research foundation for expanding into the therapeutic application of reproductive and gonadal dysfunction following acute inflammation, and to provide basic research data for verifying treatment methods that can contribute to improving quality of life after recovery from severe illness.

There are few reports on male reproductive and gonadal function after severe illness.

Clarifying the response of germ cells and testicular cells to exogenous and endogenous harmful substances

We believe that this could contribute to advanced reproductive medicine and improving quality of life after severe illness.

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1. Inoue T, Aoyama-Ishikawa M, Uemura M, Kohama K, Fujisaki N, Murakami H, Yamada T, Hirata J. The role of death receptor signaling pathways in mouse Sertoli cell avoidance of apoptosis during LPS- and IL-18-induced inflammatory conditions. J Reprod Immunol. 2023;158:103970.
2. Inoue T, Aoyama-Ishikawa M, Uemura M, Yamashita H, Koga Y, Terashima M, Usami M, Kotani J, Hirata J. Interleukin-18 levels and mouse Leydig cell apoptosis during lipopolysaccharide-induced acute inflammatory conditions. Journal of Reproductive Immunology. 2020;141:103167.
3. Inoue T, Aoyama-Ishikawa M, Kamoshida S, Nishino S, Sasano M, Oka N, Yamashita H, Kai M, Nakao A, Kotani J, Usami M. Endogenous Interleukin-18 Regulates Testicular Germ Cell Apoptosis during Endotoxemia. Reproduction. 2015;150:105-14.
4. Taketo Inoue, Michiko Ishikawa, Mikiko Uemura, Hayato Yamashita, Yuka Koga, Makoto Usami, and Joji Kotani. Involvement of endotoxin and IL-18 in apoptosis in testicular male hormone-producing cells. Igaku Tosho Shuppan. Endotoxin and Innate Immunity Research 20. Contribution of chemical biology to innate immunity. 2017; p. 31-34.
5. Taketo Inoue, Noriko Ishikawa, Satoshi Nishino, Maki Sasano, Nobuki Oka, Hayato Yamashita, Shingo Kamoshida, Atsunori Nakao, Makoto Usami, and Joji Kotani. Testicular germ cell apoptosis during endotoxemia and the role of endogenous IL-18. Igaku Tosho Shuppan. Endotoxin and natural immunity research 17. Developments in endotoxin and natural immunity: new mechanisms, diagnosis, and applications. 2014; p. 98-102.