Mouse Decidua Research Articles

Phagocytosis of collagen by mouse decidual cells.

Collagen fibrils were present within membrane-bound vacuoles in the cytoplasm of mouse decidual cells on the 7th day of pregnancy. The space between the vacuole membranes and the fibrils was narrow and frequently filled with a granular electron-dense material. The loss of banding of the collagen fibrils, their association with lysosomelike bodies, and the demonstration of acid phosphatase activity in the vacuoles indicate that the fibrils were internalized by the decidual cells and were being digested. It is suggested that phagocytosis of collagen is a mechanism of remodeling of the mouse decidua.

Kinetic and end-point microdensitometry (section biochemistry) of γ-glutamyl transpeptidase and dipeptidyl peptidase IV in the mature mouse decidua and visceral yolk sac

gamma-Glutamyl transpeptidase (EC 2.3.2.2) and dipeptidyl peptidase IV (EC 3.4.14.5) were measured in mature mouse decidual and visceral yolk sac epithelial cells by means of kinetic (continuous) and end-point (static) microdensitometry (section biochemistry). For continuous measurements a new device for starting the enzyme reaction allowed the first readings to be made already during its very early phase. Since the initial reaction rates of both peptidases were very different in the plasma membrane of decidual and also in the visceral yolk sac epithelial cells, it was difficult to select a sufficient number of cells of the same activity for representative measurements on the basis of kinetic microdensitometry. Static section biochemistry was performed also for statistical reasons, i.e., in order to obtain information about the distribution of the activities of the decidual and visceral epithelial cells and the number of measurements required to guarantee valid data. Various groups of decidual and visceral yolk sac epithelial cells with different gamma-glutamyl transpeptidase and dipeptidyl peptidase IV activities were formed. In this way, different activities of gamma-glutamyl transpeptidase were measured in the plasma membrane of the cells of the antimesometrial, intermediate, and mesometrial decidua. Compared with dipeptidyl peptidase IV, gamma-glutamyl transpeptidase was significantly more active in the plasma membrane of the antimesometrial decidual cells and microvillous zone of the visceral yolk sac epithelial cells.

Active suppression of host-vs graft reaction in pregnant mice. IX. Soluble suppressor activity obtained from allopregnant mouse decidua that blocks the cytolytic effector response to IL-2 is related to transforming growth factor-beta.

Non-Ts cells in murine allopregnancy decidua release potent immunosuppressor factors in vitro that block the action of IL-2. Previous studies have shown that both primary and secondary CTL responses are inhibited as well as the generation of Il-2 activated killer cells. In this paper we show that the suppressor factor(s) can arrest ongoing IL-2 dependent CTL responses but does not block binding of anti-IL-2R antibody or radiolabeled IL-2 to the IL-2R. The suppressive activity is associated with molecules that adhere to hydroxylapatite and con A-agarose but do not bind to activated charcoal or partition as lipids. HPLC TSK 3000 separation showed a major peak of suppressive activity at 60 to 100 kDa, with additional activity at 300 kDa, and at less than 1000. Under acid conditions, suppressive activity resolved as a major peak at 13 kDa with some residual activity at 65 kDa and at less than or equal to 1000. A specific rabbit IgG antibody to transforming growth factor-beta neutralized suppressor activity in unseparated supernatant and in the 13-kDa fraction whereas neutralizing antibodies to progesterone or PGE-2 did not affect suppression but could neutralize their respective ligands. Inasmuch as transforming growth factor-beta has a 25 kDa Mr, the 13-kDa decidua-associated suppressor factor would appear to represent a related but distinct regulatory molecule that associates with a variety of carrier molecules.

Normal murine and porcine embryos recruit NK cells to the uterus

Decidual NK cells, indistinguishable from those found in lymphoid tissues, are present in cell suspensions prepared from maternal decidua of random-bred mice between Days 6.5 and 10.5 of first gestation. The stringency of the correlation between NK cells and normal embryos during successful pregnancy is unknown. Our previous finding that active NK cells were unable to mediate lysis of fresh embryonic tissues at any stage during gestation suggests that if NK cells play a functional role in normal pregnancy it would be a noncytolytic role. Before studies on the function of uterine NK cells were undertaken, evidence that the association of NK cells with normal embryos is widespread was sought by assessing NK cell activity in cell suspensions from decidua of syngeneically mated mice, from decidua of multiparous, random-bred mice, and from the endometrium of pigs during first pregnancy. Neither parity nor maternal-fetal compatibility changed the pattern of high levels of decidual NK cell activity early in pregnancy followed by decline. Porcine NK cell activity was not detected in uterine cells isolated from cycling pigs but in pregnant animals it gradually increased during the preattachment period and reached levels greater than those in blood, postattachment (Day 28). Some of this activity was hormone dependent but sustained increases in NK cell activity required the presence of an embryo. These studies demonstrate that the association of functional NK cells with normal embryos is wide-spread during early pregnancy.

Differential expression of class II major histocompatibility complex and thy 1.2 antigens on mouse decidua

A differential expression of class II major histocompatibility complex (MHC) and Thy 1.2 antigens was detected on two morphologically distinct cell populations in short-term cultures of murine decidual tissue. Stromal type decidual cells expressed Thy 1.2, albeit transiently, and consistently lacked class II antigens. By contrast decidual macrophages expressed class II antigens and lacked Thy 1.2 antigens. Stromal type decidual cells, after culture in the presence of indomethacin, displayed no evidence of prostaglandin-mediated modulation of class II expression. These findings suggest that class II positive decidual macrophages are responsible for the antigen-presenting capacity of decidua.

Active suppression of host-versus-graft reaction in pregnant mice: VIII. The uterine decidua-associated suppressor cell is distinct from decidual NK cells

The fetus resulting from allogeneic mating expresses a variety of antigens that may serve as targets for rejection by the maternal immune system. Accumulation of non-T suppressor cells into the uterine decidua of allopregnant mice may serve to prevent such rejection. It has been previously shown that the suppressor activity in decidua during the second half of murine pregnancy is predominantly associated with a population of small lymphocytes with cytoplasmic granules that lack T-cell markers and inhibit the generation of cytotoxic lymphocytes (CTL) against paternal alloantigens both in vitro and in vivo. Since natural killer cells (NK) also possess cytoplasmic granules and may regulate the murine immune response, we examined the hypothesis that the decidua-associated non-T suppressor cell may represent a regulatory type of NK cell. Similar to NK cells, the decidua-associated suppressor cell expressed FcR for IgG. Unlike NK cells, the decidua-associated suppressor cell proved resistant to treatment with anti-asialo GM 1 + C. Sedimentation velocity examination demonstrated that decidua-associated NK activity was associated with cell population with a modal sedimentation of 4 mm/hr that was larger than the decidua-associated suppressor population. Potent suppressor cell activity was also recovered from the decidua of NK deficient allopregnant bg/bg mice. Therefore, decidua-associated NK cells and suppressor cells represent two distinct populations.

Radioautographic analysis of surface markers on decidual cells shared by cells of the lymphomyeloid tissues.

Stromal type decidual cells recovered from the murine decidua by a mild collagenase dispersion procedure contain immunoregulatory cells whose ultimate precursors may originate from the bone marrow. To explore the familial relationship of these cells with other cells of the immune system, a battery of cell surface markers recognized on lymphomyeloid cells were examined and quantitated at the morphological level on typical stromal type decidual cells of the dispersed CBA mouse decidua at 8-14 days of syngeneic pregnancy, using a sensitive radioautographic technique. Cells were either labeled directly by exposure to 125I-labeled monoclonal antibodies against Thy-1, Mac-1, or Lyt antigens or indirectly by a sequential exposure to monoclonal anti-I-Ak (Ia.17) or monospecific anti-I-JK antibodies and 125I-labeled Protein A. Decidual cells were found to be Thy-1+/- (13-73% positive, the incidence rising with advancing gestation in the decidua basalis), Mac-1+/- (present of 6-11% on day 8 and 17-32% on day 12), I-A-, 1-J-, and Lyt-. Macrophages within the decidua were Thy-1-, Lyt-, Mac-1+, and I-A+/- (present on 5-61% of cells, the incidence rising with advancing gestation).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of immune effector cells present in early murine decidua

It has been suggested that murine decidual cells act as an important immunoregulatory population localized to the pregnant uterus. We have examined early murine decidua to determine if immune effector cells occur in the decidual environment in proximity to the conceptus. High levels of natural killer (NK) cell activity were found consistently in decidual cell suspensions with peak activity occurring on Day 6.5 of gestation. NK activity declined as pregnancy proceeded and was not significant by Day 12.5 of gestation. Decidual cell suspensions did not appear to contain significant numbers of functional B or T effector cells. No antipaternal T-cell response could be demonstrated even in the decidua of immune mice. Lack of T-cell responses was attributed to the absence of T cells from decidua rather than to their inactivation because precursors of cytotoxic T lymphocytes (pCTL) could not be detected in decidual cell suspensions. Furthermore, the levels of pCTL detectable in spleen cell suspensions could not be reduced by mixing spleen cells with 7.5-day decidual cells. These results suggest that B cells and T cells may not occur in early decidua while NK cells are present and regulated independently.

Detection of macrophages and the characterization of Fc receptor-bearing cells in the mouse decidua, placenta and yolk sac using the macrophage-specific monoclonal antibody F4/80

A mouse macrophage-specific rat monoclonal antibody, F4/80, has been used to detect directly macrophages in short term cultures of mouse decidua, fetal placenta and yolk sac and to investigate the identity of Fc receptor (FcR) bearing cells in these tissues. We find that a significant proportion of FcR positive cells in decidual, placental and yolk sac tissues are macrophages as defined by the expression of the macrophage marker, F4/80 antigen. Macrophages may act as immunocompetent cells near to the maternal-fetal interface and play a significant role in the mechanism of the transfer of passive immunity from mother to fetus across the mouse yolk sac.

Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.

The mammalian fetus expresses a variety of antigens against which the maternal immune system can react and which in an allogeneic mating bears paternal transplantation antigens. Although these antigens may be expressed on the fetal trophoblast cells that contact maternal uterine decidua, the "fetal allograft" is not usually rejected. Previous studies have demonstrated the presence of nonspecific non-thymus-derived suppressor cells in the lymph nodes draining the uterus and in decidua of laboratory mice undergoing first allogeneic pregnancy. These suppressor cells appeared to be small lymphocyte cells that inhibit the generation of cytotoxic T lymphocytes (CTL) in vitro and in vivo and elaborate a nonspecific non-MHC-restricted soluble suppressor activity when cultured for 48 hours at 37 degrees C in vitro. We now report that soluble suppressor activity obtained from the decidua (DS) of allopregnant C3H/HeJ mice inhibits both the primary and secondary (memory) CTL response in vitro but does not inhibit lysis of target cells by preformed CTL. DS did not suppress the proliferation of YAC lymphoma cells, P-815 cells, or a C3H placental trophoblastoma line. Suppressor activity was obtained from anti-thy-1.2 + complement-resistant cells in the decidua, could also be obtained from the decidua of allopregnant CD1 nu/nu mice, and was associated with a single peak of activity of approximately 100,000 daltons on Sephacryl 200 chromatography. Suppression could not be overcome by adding either crude or HPLC-purified IL 2 to the mixed lymphocyte cultures in vitro, and both crude and column-purified suppressor factor inhibited the IL 2-dependent proliferation of H-Y cells (a cloned T cell line with NK activity). Furthermore, DS inhibited the IL 2-dependent generation of cytotoxic effector cells in vitro in the absence of allogeneic stimulator cells. Thus, a soluble suppressor factor obtained from non-T cells present in the decidua of successfully allopregnant mice could block the response to IL 2 and inhibit the generation of both specific and nonspecific cytotoxic effector cells. The significance of this inhibition with respect to survival of the "fetal allograft" is discussed.

Origin of the multinucleate decidual cell of the mouse.

Cytological and cytophotometrical analyses have shown that multipolar mitotic figures and multinucleate cells are present within mouse decidua. These are, moreover, found exclusively within the antimesometrially-situated decidua and contain not only excessive amounts of nuclear DNA (>4c) but also numerous sets of chromosomes (>2n). Thus, during the growth of mouse decidua, multinucleation probably results from a multipolar nuclear division without concomitant cytokinesis; polyploidisation becomes consequential upon multinucleation; and regionalisation can influence the origin of the multinucleate, polyploid condition.

Sulfated mucopolysaccharides of midgestation embryonic and extraembryonic tissues of the mouse

Incorporation of [ 35S]sulfate into sulfated mucopolysaccharides has been characterized in midgestation mouse embryo, yolk sac, trophoblast, and decidua. Enzymatic analysis indicated that chondroitin sulfates contained approximately half of the label in embryo, trophoblast, and decidua, but less than 20% in yolk sac. While the labeled chondroitin sulfate fraction of trophoblast and decidua was mainly chondroitin-4-sulfate, only embryo contained a significant proportion of labeled chondroitin-6-sulfate. The relative incorporation into embryo chondroitin-6-sulfate was also substantially higher than that observed in four adult soft tissues. Labeled dermatan sulfate was absent from the embryo and yolk sac, but small amounts might have been synthesized by the placenta. Nitrous acid degradation studies revealed that essentially all the chondroitinase resistant MPS was N-sulfated, i.e., heparan sulfate and/or heparin. Electrophoretic profiles indicate that the bulk of the N-sulfated material resembles heparan sulfate rather than heparin. Electrophoretic heterogeneity and slow migration rates relative to standard markers suggest that the majority of labeled chondroitin sulfates may be undersulfated. The different mucopolysaccharide patterns in the various tissues may reflect their specialized properties and functions.

DNA polymerases in midgestation mouse embryo, trophoblast, and decidua

The DNA polymerases of midgestation mouse embryo, trophoblast, and decidua have been examined. A low molecular weight, nuclear. DNA-dependent polymerase (D-DNA polymerase) and a higher molecular weight cytoplasmic enzyme were found in all three cell types. A DNA polymerase which utilized the poly(A) strand of oligo(dT) · poly(A) as template (R-DNA polymerase) was also found in the three cell types. This enzyme was present both in the nucleus and the cytoplasm. All enzyme levels were highest in the rapidly dividing embryonic cells, substantially lower in the DNA replicating but nondividing trophoblast cells, and lowest in the nonreplicating, nondividing decidual cells. Our observations are consistent with the idea that the nuclear and cytoplasmic D-DNA polymerases are under coordinate control. The relationship of these enzymes to DNA synthesis in vivo is discussed.