The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model.

Endometriosis is one of the most common gynecological diseases in women of reproductive age. Although cyclooxygenase (COX)-2 inhibitors are effective in the treatment of endometriosis, the adverse cardiovascular effects associated with these inhibitors have limited their use. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme downstream of COX-2 in prostaglandin E2 biosynthesis. Previously, we developed mPGES-1 knockout mice (mPGES-1−/−) and have identified for the first time the roles of ectopic lesion- and host-associated mPGES-1 in angiogenesis and the growth of endometrial tissues. When mPGES-1−/− endometrial fragments were implanted into wild type (WT) mice (mPGES-1−/−→WT), or WT fragments implanted into mPGES-1−/− mice (WT→mPGES-1−/−), the growth of the implants was suppressed at days 14 and 28 after implantation, compared toWT→WT transplantation. An even greater degree of suppression was observed in mPGES-1−/− endometrial fragments implanted into mPGES-1−/− mice (mPGES-1−/−→mPGES-1−/−). After WT-WT implantation, mPGES-1 expression was localized at the border of the implanted endometrial tissues. Microvessel density, determined by CD31 immunostaining, was markedly suppressed in the mPGES-1−/− endometrial fragments implanted into mPGES-1−/− mice, with some suppression also observed in the mPGES-1−/−→WT and WT→mPGES-1−/− groups. The expression of vascular endothelial growth factor (VEGF-A) was significantly reduced in mPGES-1−/− endometrial tissues implanted into mPGES-1−/− mice at days 14 and 28, in comparison to the WT→WT group. These results suggested that mPGES-1 enhanced angiogenesis and growth of the endometrial implant, and indicate that mPGES-1 may be a good therapeutic target for endometriosis.