Characterization of cytokine production by the metrial gland and granulated metrial gland cells

Abstract

The metrial gland and its population of bone marrow-derived, large, granulated, lymphocyte-like cells, termed granulated metrial gland (GMG) cells, are consistent but poorly understood, decidua-associated features of pregnancy in the mouse and other species. Decidua, a complex maternal tissue, is thought to be a source of cytokines important for placental development. Thus, it is important to determine if lymphokine or cytokine production is among the activities of the metrial gland and GMG cells. Media conditioned by culture of either metrial gland explants or migrating GMG cells were evaluated for various cytokine activities. At least four activities were present: CSF-1, IL-1, a factor promoting proliferation of DA-1 cells that was not GM-CSF, IL-3 or erythropoietin and an activity cytotoxic to the CSF-1-dependent macrophage cell line 5/10.14. CSF-1 and IL-1 appeared to be products of the GMG cells. Cytokines not present at detectable levels included IL-2, IL-4, TNF-α and TGF-β. Qualitatively, the cytokine profiles remained constant throughout days 8–16 of gestation, mRNA from migratory GMG cells was isolated and assayed for eleven cytokine mRNAs by polymerase chain reaction-based amplification of cDNA synthesized from mRNA. GMG cell RNA contained transcripts for LIF and CSF-1 but did not contain transcripts for GM-CSF, G-CSF, IL-2, IL-3, IL-4, IL-6, IL-7, IFN-γ or TNF-α. TGF-β transcripts were detected in occasional samples at very low levels. Since GMG cells are highly mobile cells that migrate throughout the placenta and into trophoblast-lined maternal blood spaces, their function in pregnancy may involve the delivery of very localized differentiation or growth regulatory signals to the developing fetal trophoblast and placenta.