Cyclooxygenases and prostaglandin E synthases in preimplantation mouse embryos

Abstract

Prostaglandin E 2 (PGE 2 ) is shown to be essential for female reproduction. Cyclooxygenase (COX) is a ratelimiting enzyme in prostaglandin synthesis from arachidonic acid and exists in two isoforms: COX-1 and COX-2. Prostaglandin E synthase (PGES) is a terminal prostanoid synthase and can catalyse the isomerization of the COX product PGH 2 to PGE 2 , including microsomal PGES-1 (mPGES-1), cytosolic PGES (cPGES) and mPGES-2. This study examined the protein expression of COX-1, COX-2, mPGES-1, cPGES and mPGES-2 in preimplantation mouse embryos by immunohistochemistry. Embryos at different stages collected from oviducts or uteri were transferred into a flushed oviduct of non-pregnant mice. The oviducts containing embryos were paraffin-embedded and processed for immunostaining. COX-1 immunostaining was at a basal level in zygotes and a low level at the 2-cell stage, reaching a high level from the 4-cell to blastocyst stage. COX-2 immunostaining was at a low level at the zygote stage and was maintained at a high level from the 2-cell to blastocyst stages. A low level of mPGES-1 immunostaining was observed from the zygote to 8-cell stages. The signal for mPGES-1 immunostaining became stronger at the morula stage and was strongly seen at the blastocyst stage. cPGES immunostaining was strongly observed in zygotes, 2-cell and 8-cell embryos. There was a slight decrease in cPGES immunostaining at the 4-cell, morula and blastocyst stages. mPGES-2 immunostaining was at a low level from the zygote to morula stages and at a high level at the blastocyst stage. We found that the COX-1, COX-2, mPGES-1, cPGES and mPGES-2 protein signals were all at a high level at the blastocyst stage. PGE 2 produced during the preimplantation development may play roles during embryo transport and implantation.

Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target

“…Additional studies in hamsters showed that PGE 2 but not PGI 2 is the major prostaglandin at implantation sites where COX-2 and mPGES-1 but not PGI synthase are expressed . A detailed study on the PGE 2 -forming enzymes driving the development of the blastocyst in mice has also been reported (Tan et al, 2005). Moreover, a study in rats showed that, as in mice, both PGE 2 and PGI 2 have important roles in implantation (Cong et al, 2006).…”

Diverse Roles of Prostaglandins in Blastocyst Implantation

“…During development, blastocyst expresses multiple factors and their receptors in response to sex steroids and growth factors, which in turn regulate blastocyst growth and participate in the signal exchange with the receptive endometrium. Hormones and factors expressed include the preimplantation factor (PIF) [144], chorionic gonadotrophins (cG) [145], leukemic inhibitory factor (LIF) [146], heparin-binding epidermal growth factor (HB-EGF) [147], and PGs [148]. …”

“…In addition to PGI 2 , PGE 2 also plays important role in embryo development [148]. mPGES mRNA was detected at all stages during preimplantation embryo development [83] while cPGES expression has been reported in 2-cell, 4-cell, and 8-cell, morula, and blastocyst stages [16] in mice.…”

Oncostatin M expression in the mouse uterus during early pregnancy promotes embryo implantation and decidualization

“…PGE 2 can be synthesized and secreted by mouse blastocysts [35]. We are wondering how Osm acts on embryo implantation.…”