Reproduction involves tightly regulated series of events and the immune system is involved in an array of reproductive processes. Disruption of well-controlled immune functions leads to infertility, placental inflammation, and numerous pregnancy complications, including preeclampsia (PE). Inflammasomes are involved in the process of pathogen clearance and sterile inflammation. The NLRP3 inflammasome is a key mediator of sterile inflammation induced by various types of damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is involved in pregnancy dysfunction, including PE. Many DAMPs (uric acid, palmitic acid, extracellular vesicles, and cell-free DNA, and fatty free acids) are increased and associated with pregnancy complications. This review focuses on the role of the NLRP3 inflammasome in pregnancy complications, especially PE.

Hypertensive disorders of pregnancy (HDP) are still life-threatening diseases.

However, the pathogenesis of HDP has progressed rapidly in the last 20 years. Recently ‘Two Step Theory’ has been proposed and widely accepted. In the theory, soluble VEGF receptor 1(sFlt-1) plays crucial roles. Thus far, many HDP model animals have been exploited and accelerated the HDP research. In the research of HDP, many Japanese researchers have occupied important parts in both in vitro and in vivo experiments, in addition to clinical discoveries. In this review, we explain about the relations between HDP and sFlt-1, and then introduce mainly two kinds of model mice of HDP by our groups.

Spermatid and sperm do not appear in the seminiferous epithelium until puberty, when immune tolerance has already been established. Therefore, there are various autoimmunogenic antigens in testicular germ cells(TGC)recognized as foreign by the self-immune system. However, the blood-testis-barrier formed by Sertoli cells protect autoimmunogeneic spermatozoa from attack by the self-immune system. We previously showed that immunization of susceptible mice with TGC alone is sufficient to induce autoimmune orchitis without the use of any adjuvant. In the present study, we tried to identify TGC-specific autoantigens by phage display method, followed by mouse TGC phage library. The results showed that twenty genes were detected as candidate genes of autoantigens. Additionally, we analyzed more detailed gene expressions of these autoantigens by real-time PCR. Eight of twenty genes were specifically expressed in TGC. We generated plasmids with a Flag-tag of these nine candidate genes, and human embryonic kidney(HEK)293 T cells that transduced these plasmids were cultured to obtain these candidate gene expressing proteins. The proteins produced by HEK293T cells were reacted with TGC-immunized mouse serum antibody, and then detected by western blot analysis. As a result, two TGC-specific genes tested positive. These results indicate that these two TGC-specific genes are critical for induction of the autoimmune orchitis.