Expression of opioid receptors and ligands in pregnant mouse uterus and placenta

The endogenous opioid system has been implicated in the regulation of hormonal secretion, pain perception, and uterine contractility during pregnancy, but there is only limited information about the cellular location of opioid receptor and opioid peptide gene expression in the pregnant rodent uterus and placenta. In this study, we have used in situ hybridization to identify expression sites of mRNAs encoding the delta (delta), kappa (kappa), and mu ( micro) opioid receptors as well as the endogenous opioid peptide precursors proenkephalin (PENK), prodynorphin (PDYN), and proopiomelanocortin (POMC) in pregnant mouse uterus and placenta. Soon after implantation, all three opioid receptor genes as well as POMC and PENK, but not PDYN, were detected in the uterine environment. Each expressed gene exhibited a distinct expression pattern that was generally retained until late gestation. The delta receptor and POMC were coexpressed in the trophoblast giant cells, which remained the only cells of the placenta/uterus to express these two genes throughout gestation. Cells expressing kappa receptors were absent from the placenta but instead were found in the basal part of the decidualized uterine endometrium. While kappa and micro receptors were transiently expressed in the uterine myometrium (until embryonic day 8.5), substantial levels of PENK were continuously detected in this region until at least embryonic day 18. In addition, complementary expression of the micro receptor and PENK genes in the uterus was detected. Taken together, these results suggest multiple roles for the opioid receptors and opioid peptides in maternal adaptation to pregnancy and in supporting embryo growth.