Abstract: 78

THE MOUSE BLASTOCYST IS A TARGET FOR HISTAMINE LIGAND-RECEPTOR SIGNALING.

BC Paria^{1 *}, X Zhao¹ , SK Das^{1 *}
Departments of Molecular and Integrative Physiology, and Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, Kansas. ¹

Histamine is thought to play an important role in embryo development and implantation. But the source of histamine remained unresolved. Recently, we have established that uterine luminal epithelium (LE), but not the resident mast cells, is the major source of histamine during early pregnancy in the mouse (Endocrinology 139: 3958-3966,1998). However, the possible target(s) of uterine histamine action is not known. Histamine mediates its effects via three types of histamine receptors, H1, H2 and H3. Northern blot and in situ hybridization studies failed to detect expression of H1 and H2 receptors in the preimplantation mouse uterus. Using RT-PCR, we observed that H2 receptor mRNA is expressed at the blastocyst stage, while H1 receptor and histamine decarboxylase mRNAs are not expressed in the preimplantation embryo. Autoradiographic studies demonstrated that H2 receptor ligand binding signals are present in the trophectoderm cells, while they are absent in the inner cell mass cells. Moreover, both RT-PCR and autoradiographic studies demonstrated that H2 receptor expression is down regulated in dormant blastocysts, but is upregulated in dormant blastocysts after E₂ activation in vivo. These results suggest a possible interaction of the blastocyst H2 receptors with uterine histamine. Indeed, our in vitro studies showed that an H2 receptor agonist promotes blastocyst zona hatching. Further, day 4 blastocysts exposed to H2 receptor antagonists for 6 h failed to implant when they were transferred into uteri of day 4 pseudopregnant recipients. Collectively, our results demonstrate that histamine produced by uterine LE participates in implantation in a paracrine manner via its activation of H2 receptors expressed in the blastocyst. NIH Grant# HD35114 to BCP.

    This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.