Kosuke Oikawa

A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is an endocrine disruptor that produces a variety of toxic effects. We have isolated a mouse homolog of the hWAPL gene, termed mouse WAPL (mWAPL), as a target of TCDD by cDNA representational difference analysis from mouse embryonic stem cells. A statistically significant increase in mWAPL expression was observed at 0.1 μM TCDD in AhR−/− mouse embryonic fibroblast cells. Interestingly, at 1 μM TCDD, mWAPL mRNA levels decreased in AhR+/+ cells, but further increased in AhR−/− cells. hWAPL and mWAPL were highly expressed only in testes among normal tissue samples, and we observed mWAPL localization in the synaptonemal complex of testicular chromosomes. In addition, mouse testes decreased the expression of mWAPL mRNA after a single intraperitoneal injection of TCDD. Thus, mammalian WAPL such as hWAPL and mWAPL may be involved in spermatogenesis and be target genes mediating the reproductive toxicity induced by TCDD.

Increased expression of IgE-dependent histamine-releasing factor in endometriotic implants

A complex network of cytokines mediates the immunoregulatory responses leading to endometriosis. Recent intensive studies suggest that monocyte and T cell chemoattractants contribute to the inflammatory environment of endometriotic implants. The relationship between the inflammation present during endometriosis and the development of endometriotic implants in the peritoneal cavity remains unclear. On the other hand, the association between endometriosis and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD; dioxin) exposure has been discussed in recent years, and our previous results revealed that IgE‐dependent histamine‐releasing factor (HRF) is inducible by TCDD. The present study aimed to clarify the expression, localization, and function of HRF in endometriosis. Northern blot analysis demonstrated that HRF is overexpressed in endometriotic implants. RT‐PCR with Southern blot analysis, however, showed that HRF overexpression was not always accompanied by CYP1A1 induction in endometriotic implants, suggesting that HRF is inducible in endometriosis without exposure to TCDD. HRF is also inducible by macrophage colony‐stimulating factor (M‐CSF). Immunohistochemistry showed CD68‐positive macrophages in the stroma of endometriotic implants, adjacent to regions with prominent HRF accumulation. HRF‐overexpressing cells exhibited high implantation efficiency in comparison to control cells when the cells were injected into the peritoneal cavities of nude mice. These results suggest that the accumulation of macrophages in endometriotic implants induces HRF; the overexpression of HRF accelerates the growth of endometriotic implants. Copyright