Gene expression studies of murine pregnancy associated granulated metrial gland and decidual cells
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Abstract
During pregnancy in viviparous mammals, the maternal decidua develops between the embryo and the uterine endometrium. This dissertation describes research on two different cell types present within the rodent decidua during pregnancy, namely, granulated metrial gland (GMG) cells and decidual cells;GMG cells are natural killer cells that proliferate and differentiate within the murine uterus during pregnancy. Their differentiation is associated with the accumulation of cytolytic mediators within cytoplasmic granules. The signaling mechanisms required for GMG cell differentiation, however, are largely unknown. In this study, expression of the genes coding for granzymes D, E, F, and G (granzymes D-G) was found to be developmentally regulated in GMG cells during pregnancy. In addition, granzymes D-G were expressed in late gestation, in contrast to the mid-gestational expression of granzyme A. Expression of the IL-2 receptor [beta] and [gamma] chains, as well as the IL-15 receptor [alpha] , was detected in the uterus at the time when granzymes D-G are expressed. Finally, granzymes D-G were shown to be upregulated by IL-2 and IL-15 in cultures containing GMG cells. These results demonstrate that IL-2 and/or IL-15 may regulate GMG cell differentiation in vivo, and that granzymes may have several functions during murine pregnancy;Decidual regression is an apoptotic event that remodels the murine uterus during pregnancy. Recent investigations have suggested that members of the Bcl-2 family may be involved in decidual regression. The purpose of the second study was to examine the spacial and temporal expression of the cell death regulators, Bax and Bcl-2, during pregnancy in the mouse uterus. The bax [alpha] transcript was expressed at its highest levels between days 1-5 of pregnancy and declined steadily thereafter. Bcl-2 mRNA, however, was undetectable in the uterus. Using an immunohistochemical approach, Bax was observed in pre-decidual stromal cells on day 3 of gestation, three days prior to antimesometrial decidual apoptosis. At day 9.5, regression in the antimesometrial decidua is complete, whereas mesometrial decidual regression is forthcoming. In the day 9.5 uterus, Bax expression was restricted to the mesometrial decidua. These results suggest that Bax, a cell death effector, may regulate decidual cell apoptosis during murine pregnancy.