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M B Parr

Publications and source records attributed to M B Parr.

At least 55 records · Page 3Linked to original sources
PubMed1988

Endocytosis in the uterine luminal and glandular epithelial cells of mice during early pregnancy.

We have localized horseradish peroxidase (HRP) in the mouse uterus after intravenous administration on days 1 and 5 of pregnancy in an effort to understand how serum proteins reach the uterine lumen. Direct movement of HRP into uterine and glandular lumina was blocked by the epithelial tight junctions on both days. In luminal and glandular epithelial cells at both times, HRP was localized in endocytic vesicles along the basolateral membranes, multivesicular bodies (mvb), elongated dense bodies below the nucleus (bdb), and many small vesicles near the apical surface of the cells. The uptake of HRP was most extensive in the luminal epithelium on day 1: the number of tracer-containing apical vesicles and bdb was largest, and there were also clusters of vesicles containing the tracer above the nucleus. Acid phosphatase was localized on day 1 in mvb and bdb in both cell types, indicating that these structures are lysosomes. It appeared that HRP followed two pathways after basolateral endocytosis by the epithelial cells: it was transported to the apical region of the cells, where it was present in small vesicles that may release their contents into the uterine or glandular lumina, or it was transported to lysosomes. To investigate whether macromolecules may be transported from the uterine lumen to the stroma, we also studied endocytosis at the apical pole of luminal epithelial cells after intraluminal injection of HRP. There was no detectable uptake of HRP from the lumen on day 1, and no tracer was detected in the intercellular spaces or basement membrane region. On day 5, a large amount of HRP was taken up from the lumen into apical endocytic vesicles, mvb, and dense bodies, but tracer was not present in the Golgi apparatus, lateral intercellular spaces, or the basement membrane region at the times studied. These observations indicate that there was no transport of luminal macromolecules to the uterine stroma on day 1, while the possibility of transport on day 5 requires further study.

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PubMed1988

Deposition of C3 on bacteria in the mouse uterus after mating.

A previous study demonstrated that several species of bacteria were present in the mouse uterine lumen on the day after mating, and that many of these bacteria had immunoglobulins bound to their surface. Neutrophilic leukocytes containing phagocytosed bacteria were also present in the lumen. Since bacteria are phagocytosed efficiently only when they are opsonized by the binding of specific antibody or C3b or both to their surface, we investigated whether the uterine bacteria were coated with C3. Immunolabeling demonstrated that an antigenic portion of C3, possibly C3b, was bound to many of the uterine bacteria. This observation suggests that bacteria in the mouse uterus after mating may be opsonized by both antibody and complement and that phagocytosis of these bacteria by neutrophils may play an important role in returning the uterus to an aseptic state before implantation.

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PubMed1988

Anti-bacterial IgA and IgG in mouse uterine luminal fluid, vaginal washings and serum.

A previous study demonstrated that mouse uterine horns contained bacteria of several species on the morning after mating, and immunolabeling showed that many of these bacteria were coated with immunoglobulins. In the present study we used an ELISA technique to detect naturally-occurring antibodies against bacteria in mouse uterine luminal fluid, vaginal washings and serum. Each fluid contained specific IgA and/or IgG antibodies to five of the six bacterial species recovered from the uterus after mating. The uterine fluid antibodies that bound to the bacteria were mainly IgA molecules, while those in the serum were mainly IgG. Naturally-occurring bacterial antibodies in mouse uterine luminal fluid may play a role in protecting the endometrium against microbial infections.

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PubMed1988

A comparison of specific antibody responses in mouse vaginal fluid after immunization by several routes.

Mice were immunized with a protein antigen, horse ferritin, by eight different routes and the immune responses in the reproductive tract were compared by measuring specific IgA and IgG in vaginal fluid and by localizing anti-ferritin plasma cells in uterine horns, cervix and vagina. The eight routes of immunization were: subcutaneous with Freund's adjuvant (s.c.), intragastric (i.g.), intravaginal (i.v.), s.c.-i.g., s.c.-i.v., i.g.-i.v., i.v.-i.v. and s.c.-i.g.-i.v. The largest overall response, considering both IgA and IgG antibodies, was obtained by s.c. priming with ferritin in adjuvant followed by i.v. boosting. Intravaginal immunization also boosted priming by the i.g., s.c.-i.g. and i.v. routes, but the response to i.v. immunization alone was weak. All i.v. immunizations stimulated mainly IgA antibody responses in vaginal fluid. Specific plasma cells, mostly of the IgG isotype, were present in the vaginal fornix of several mice in the s.c.-i.v. and s.c.-i.g.-i.v. groups, but none were detected there in any other group and they were only rarely observed in the uterine horns. The results provide data on the relative effectiveness of different routes of immunization in producing a humoral immune response in vaginal fluid against a non-replicating antigen.

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PubMed1988

Immunohistochemical localization of prostaglandin synthase in the rat uterus and embryo during the peri-implantation period.

Prostaglandins (PGs) appear to have a role in the appearance of the increased uterine vascular permeability and subsequent decidualization observed at implantation in many species. However, the sites of production of these PGs have not been clearly established. To clarify the PG synthetic capacity of the blastocyst and the various types of cells in the uterus at implantation, we have studied the immunohistochemical localization of PG synthase in the rat blastocyst on Days 5 to 7 and uterus on Days 1, 4, 5, 6, and 7 of pregnancy. Labeling of PG synthase was negligible in the uterus on Day 1 of pregnancy. On Day 4, there was increased labeling in the luminal and glandular epithelium, in stromal cells adjacent to the luminal epithelium, and in blood vessels and some leukocytes. PG synthase was detected in the blastocysts on Days 5 to 7, but there was a gradual loss of label in the luminal and glandular epithelial cells during this period. Early differentiating stromal cells adjacent to the luminal epithelium in the implantation site on Day 5 showed bright labeling, whereas peripheral stromal cells were only slightly labeled. By Day 7, the differentiated cells of the primary decidual zone showed little or no label, but cells in the secondary decidual zone were brightly labeled. These results indicate that PG synthase is present in the rat blastocyst and in several kinds of uterine cells, and that its localization in uterine cells changed markedly during the implantation process.

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PubMed1987

Apoptosis as the mode of uterine epithelial cell death during embryo implantation in mice and rats.

An ultrastructural study of mouse and rat embryo implantation sites was undertaken to determine whether the uterine luminal epithelial cells surrounding the blastocyst exhibited the morphologic characteristics of apoptotic or necrotic cell death. In both species the epithelial cells exhibited all of the characteristics of apoptosis, including surface blebbing, shrinkage and fragmentation of the cells, condensation of chromatin, and indentation and fragmentation of nuclei. Cytoplasmic organelles remained morphologically intact, and the cytoplasm maintained normal or increased staining density. Also, the epithelial cells and cell fragments were phagocytosed by the adjacent trophoblast cells. The epithelial cells did not exhibit the characteristics of necrotic cell death, such as swollen cells and mitochondria, damaged surface membranes, and disintegrated cytoplasmic organelles. We conclude that uterine epithelial cells surrounding mouse and rat embryos during implantation undergo apoptotic cell death leading to their phagocytosis by trophoblast cells.

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PubMed1987

Localization of a pore-forming protein (perforin) in granulated metrial gland cells.

Several studies have suggested that the granulated metrial gland (GMG) cells of the metrial gland (MG) may be natural killer (NK)-like cells. The cytotoxicity of NK cells involves secretion of a pore-forming protein termed perforin, which can polymerize on the target cell membrane to form transmembrane pores that are thought to be involved in target cell death. In the present study, we used an antiserum against perforin to determine whether this protein can be detected immunohistochemically in GMG cells. Mouse uteri were fixed by vascular perfusion with several fixatives on Day 14 of pregnancy, and tissue sections were labeled by an indirect immunofluorescence method. Specific perforin labeling was detected in GMG cells throughout the MG, in the decidua basalis, and in the labyrinthine placenta. The presence of perforin in GMG cells supports the suggestion that they may be NK-like cells.

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PubMed1986

The ultrastructure of the rat primary decidual zone.

The rat primary decidual zone (PDZ) is a transitory, avascular region of transformed fibroblasts surrounding the implanting embryo. Tracer studies have indicated that the PDZ is selectively permeable to macromolecules, permeability decreasing with increasing molecular weight of the tracer. To clarify the morphological basis of the permeability barrier, we have studied the ultrastructure of the PDZ with particular emphasis on the intercellular features and cellular junctions. The cells of the PDZ were large and tightly packed; their apposed membranes showed extensive interdigitations in some regions, but elsewhere they were relatively straight. Tight junctions, gap junctions, and desmosomelike junctions were observed between decidual cells. The tight junctions usually consisted of one or two points of membrane fusion, and they were oriented both parallel and perpendicular to the long axis of the PDZ. These junctions were frequently associated with gap junctions. Scattered pockets of dilated extracellular space between decidual cells contained collagen fibrils and an amorphous, dense material. These extracellular components were also sequestered by the decidual cells in deep invaginations of the cell surface that were continuous with the extracellular space. Decidual cells also exhibited flangelike processes that penetrated the basal laminae of the adjacent epithelium and capillary endothelium. Our present observations indicate that decidual cells are connected by tight junctions, and a previous study demonstrated that macromolecules up to 40 kDa readily cross the PDZ; hence, the tight junctions appear to be discontinuous. We suggest that the structures restricting the movement of large macromolecules (66 kDa and larger) across the PDZ from blood vessels to the embryo may include discontinuous tight junctions, membrane interdigitations, and amorphous intercellular material.

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PubMed1986

The effect of sperm immunization in the gastrointestinal tract on anti-sperm antibody production and fertility in female mice.

The present investigation studied the effects of sperm immunization in the gastrointestinal tract on anti-sperm antibody production and fertility in female mice. For comparative purposes, mice were also immunized with sperm intraperitoneally. Intraperitoneal immunization with 5 X 10(6) washed epididymal and vas deferens sperm 3 times per week for 7 wk produced anti-sperm IgG in plasma at 1:20,000 and in vaginal washings at 1:100 as determined by ELISA. Such mice have been shown previously to have reduced fertility. In comparison, mice immunized intragastrically with 5 X 10(6) sperm once per week for 11-14 wk had anti-sperm IgA in vaginal washings at only about 1:8 as determined by ELISA. After mating at the 14th wk these mice delivered 6.5 +/- 1.4 pups, which was not significantly different from the 7.1 +/- 1.1 pups delivered by an untreated control group. Mice immunized twice intragastrically and once intravaginally during a 25-day period had no detectable anti-sperm IgA in vaginal washings by ELISA. These mice delivered 9.7 +/- 1.2 pups after mating beginning on day 32, as compared to 9.7 +/- 0.8 pups in a PBS-sham immunized group. Mice immunized once intraduodenally and then once intraperitoneally 14 days later delivered 10.4 +/- 0.9 pups after mating 10-14 days after the second immunization, while a similar group of mice whose primary sperm immunization was directly into Peyer's patches delivered 9.0 +/- 1.4 pups. We could not detect anti-sperm IgG or IgA bound to sperm in the uterine or oviduct lumen using immunohistochemical labeling after any of the groups of immunized mice were mated.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Uptake of immunoglobulins and other proteins from serum into epithelial cells of the mouse uterus and oviduct.

The transport of immunoglobulins into the lumen of the female reproductive tract is not well understood, especially in the case of IgG. In mice, there are conflicting reports concerning the presence of immunoglobulins in uterine luminal and glandular epithelial cells, and immunoglobulins have not been detected in the luminal epithelial cells of the oviduct. In the present study we detected both IgA and IgG in uterine luminal and glandular epithelial cells on day 1 of pregnancy by immunolabeling. Also, we observed that fluorescein-conjugated mouse and bovine IgG and other proteins were taken up into vesicles in uterine luminal and glandular epithelial cells after intravenous administration. These observations indicate that both kinds of epithelial cells take up immunoglobulins from the interstitial fluid on day 1 of pregnancy, and that the cells may therefore be involved in the transport of immunoglobulins and other proteins to the uterine lumen at that time. In the oviduct, we detected IgA and IgG in vesicles in the luminal epithelial cells of the preampulla by immunolabeling, and we observed fluorescein-conjugated IgA and IgG in similar vesicles after intravenous administration. The presence of IgA and IgG in vesicles in the epithelial cells of the preampulla, together with the previous demonstration of plasma cells of both isotypes and large amounts of interstitial immunoglobulins in the lamina propria of this segment, suggests that the preampulla of the oviduct may be an important site for the local immune system in the mouse female genital tract.

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PubMed1986

Permeability of the primary decidual zone in the rat uterus: studies using fluorescein-labeled proteins and dextrans.

The primary decidual zone (PDZ) is a transitory avascular region of transformed fibroblasts surrounding the luminal epithelium at the implantation site. Since this zone may restrict the passage of immunoglobulins, cells, nutrients, and other substances from maternal blood to the epithelium and embryo from Days 6 to 8 of pregnancy, it was of interest to study its permeability to blood-borne tracers. Fluorescein isothiocyanate (FITC)-labeled macromolecules were administered i.v. on Days 6 to 9 of pregnancy. The tracers included dextran (17 kDa), horseradish peroxidase (40 kDa), ovalbumin (45 kDa), dextran (66 kDa), bovine serum albumin (BSA: 66 kDa), dextran (156 kDa), bovine immunoglobulin G (IgG; 160 kDa), and apoferritin (450 kDa). Ten minutes after administration on Days 6 or 7, FITC-labeled tracers of molecular masses of 45 kDa or less were localized in the intercellular spaces of the PDZ and in the blastocyst in small amounts. Tracers with molecular masses of 66 kDa were not detected in these regions up to 1 h after administration but were present in small amounts at 5 h. The 156 kDa and 160 kDa tracers were absent or present only in very small amounts in the PDZ and blastocyst up to 7 h after injection and apoferritin was completely absent at this time. By Day 9 the PDZ had regressed and maternal blood spaces were present adjacent to Reichert's membrane. One hour after administration on Day 9, large quantities of labeled BSA, IgG, and apoferritin appeared in the yolk sac endoderm but not in the underlying embryonic cells. These observations indicate that the PDZ is selectively permeable to blood-borne tracers on Days 6 and 7 of pregnancy, with permeability decreasing with increasing molecular mass. By restricting the passage of high molecular weight substances such as immunoglobulins, microorganisms, and immunocompetent cells, the PDZ may serve a protective function for the embryo, which is no longer protected by the uterine epithelium and has not yet fully developed its own protective layers, especially the yolk sac and Reichert's membrane.

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PubMed1986

The permeability of the primary decidual zone in the rat uterus: an ultrastructural tracer and freeze-fracture study.

The rat primary decidual zone (PDZ) is a transitory avascular region of transformed fibroblasts surrounding the implanting embryo. Studies using fluorescein-labeled tracers have shown that the PDZ is selectively permeable to macromolecules, permeability decreasing with increasing molecular weight. In the present study we investigated the morphologic basis of the permeability barrier. Horseradish peroxidase (HRP) or HRP-labeled immunoglobulin G (IgG-HRP) was administered i.v. to rats on Day 7 of pregnancy, and the animals were killed 30 min to 2 h later. The reaction product of HRP was the same density in uterine blood vessels as in the intercellular spaces of the endometrium and PDZ at 30 min and 1 h after administration. Two hours after administration, the reaction product of IgG-HRP was dense in uterine blood vessels, much less dense in the interstitial spaces of the endometrium, and was not detected in the PDZ. There was an abrupt change in the density of the IgG-HRP reaction product at the intercellular clefts between endothelial cells, where cellular junctions were observed in control tissue. This suggests that the passage of large macromolecules from blood to the implantation chamber is limited initially by cellular junctions between capillary endothelial cells. The exclusion of IgG-HRP from the PDZ indicates that an additional barrier(s) to macromolecules in this region. Lanthanum nitrate tracer was uniformly present throughout the intercellular spaces of the PDZ except at tight junctions between decidual cells. Freeze-fracture replicas of the PDZ showed tight junctions that varied from single strands to interconnected networks of strands oriented mainly parallel to the long axis of the PDZ. Some strands were discontinuous. The tight junctions between decidual cells appear to be functionally discontinuous because HRP readily penetrated the PDZ, but such junctions may retard larger macromolecules such as IgG-HRP. The biological significance of the permeability barrier of the PDZ is discussed.

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PubMed1986

Effects of oestradiol-17 beta and progesterone on the number of plasma cells in uteri of ovariectomized mice.

Immunoglobulins A and G were localized by immunoperoxidase labelling in uteri of ovariectomized mice treated with oestradiol-17 beta and progesterone. The administration of oestradiol or progesterone alone to ovariectomized mice for 3 days increased the number of IgA plasma cells from about 1 to 14 per histological section. When the two hormones were administered simultaneously for 3 days the number of plasma cells per section was equal to or greater than with either hormone alone. Treatment with oestradiol followed by progesterone in a sequence that prepares the uterus for implantation resulted in about 31 IgA plasma cells per section. Counts of IgG plasma cells showed similar trends but the numbers were smaller. The results indicate that progesterone increases rather than decreases the number of plasma cells in the mouse uterus. This is consistent with observations on intact mice during oestrus and pregnancy and suggests that the marked increase in endometrial plasma cells at the time of implantation in mice is a response to progesterone acting on an oestrogen-primed uterus.

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PubMed1985

Localization of immunoglobulins in the mouse uterus, embryo, and placenta during the second half of pregnancy.

Throughout the second half of pregnancy in mice there were many plasma cells containing immunoglobulins A (IgA) and G (IgG) in the uterine endometrium. There was intense staining of IgA in uterine glands at all stages, but little staining of IgG. The staining of both immunoglobulins (Igs) in the luminal epithelium was moderate to dark on day 11, slight on day 14, and increased from day 16 to term. From day 14 to term the endometrium exhibited folds or villi around each placenta. The cores of the villi contained many plasma cells of both isotypes, and the staining of extracellular Igs in the villous cores was darker than in nonvillous endometrium. Both Igs were detected in the uterine lumen, and in visceral and parietal yolk sac endoderm cells at all stages. Near term, the staining of Igs in the visceral yolk sac was darkest in the peripheral villous portion adjacent to the endometrial villi. From day 14 to term IgG was present in the visceral yolk sac mesenchyme and embryo, consistent with its transfer from the uterine lumen to the embryo via the vitelline circulation. In contrast, IgA was not detected in yolk sac mesenchyme until day 19, when only slight staining was observed, and IgA was never detected in the embryo. Most trophoblast giant cells contained both Igs on day 11. During the remainder of pregnancy, there was staining of both Igs in labyrinthine trophoblast and in a few giant cells adjacent to the parietal yolk sac on the placenta, but there was negligible staining in the spongiotrophoblast region. Our observations suggest that the local immune system in the mouse uterus may protect the embryo during the second half of pregnancy by secreting anti-microbial immunoglobulins A and G into the uterine lumen surrounding the visceral yolk sac, and may at the same time contribute to the transfer of maternal IgG to the embryo via the yolk sac and vitelline circulation.

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PubMed1985

Secretory immunoglobulin binding to bacteria in the mouse uterus after mating.

Bacteria of several species were present in the mouse uterus on the morning after mating, as demonstrated by bacterial cultures and microscopic examination of Gram-stained uterine luminal contents. The similarity between bacteria cultured from the vagina before mating and from the uterus after mating suggested that bacteria were introduced into the uterus from the vagina, possibly by coitus. The bacteria were cleared from the uterus about two days after mating. Immunohistochemical labeling of smears of the luminal contents on the morning after mating demonstrated IgA, IgG, and possibly IgM bound to many of the bacteria. The bacteria were often agglutinated, and there was a correlation between the intensity of immunoglobulin labeling on bacteria and the extent of agglutination. The amount of antibody bound to bacteria in multiparous mice was about the same as in mice that had not been mated previously. We observed both IgG and IgA on bacteria when organisms from vaginal cultures were incubated for 60 min in the uteri of estrogen-primed, virgin, female mice. This indicated that the uterus was the source of at least part of the immunoglobulins bound to bacteria. We did not demonstrate that the immunoglobulins bound to bacteria were specific anti-bacterial antibodies, but the binding persisted through three washing steps and there was no immunoglobulin binding to sperm in the same preparations. Neutrophils in the uterine lumen on the day after mating contained phagocytosed bacteria. These results suggest that the secretory immune system in the female mouse reproductive tract may play a role in returning the uterus to an aseptic state after mating by at least three mechanisms: direct blocking of attachment sites involved in bacterial binding to mucosal epithelium, agglutination of bacteria and thus reduction in the number of organisms available for binding to the epithelium, and opsonization of bacteria for phagocytosis by neutrophils.

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PubMed1985

Immunohistochemical localization of immunoglobulins A, G and M in the mouse female genital tract.

The localization of immunoglobulins A, G and M (IgA, IgG, IgM) in the mouse genital tract was studied by immunoperoxidase techniques at oestrus, on the day of mating and at the time of implantation. In the horns and body of the uterus, IgA and IgG were located in plasma cells in the endometrium surrounding uterine glands and in the gland lumina. The numbers of these plasma cells increased markedly between Day 1 and Days 4 and 5 of pregnancy and the ratio of plasma cells containing IgA and IgG was about 3 or 4 to 1 at all stages. Area measurements indicated that the increased number of plasmacytes was not due to an increase in the amount of endometrial, myometrial or glandular tissues. Plasma cells were not detected in the cervix and vaginal fornix at oestrus and Day 1, but a few were present on Day 5. In the oviduct, plasma cells containing IgA and IgG were present only in the preampulla and both immunoglobulins were present in the extracellular space of the lamina propria only in this region. No IgM was detected in any part of the reproductive tract at any of the times studied. Uteri on Day 1 of pregnancy contained bacteria of several kinds, some of which were aggregated and coated with IgA. This suggests that the uterine lumen at this time may contain specific anti-bacterial IgA antibodies. Our observations indicate that the horns and body of the uterus and the preampulla of the oviduct are major sites of a local immune system in the female mouse genital tract.

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PubMed1983

Relationship of uterine closure to ovarian hormones and endocytosis in the rat.

Ovariectomized rats were treated with various hormonal regimens. The first stage of uterine closure and epithelial cell endocytosis were observed in ovariectomized rats treated with progesterone or progesterone after oestrogen priming but not in hormonally untreated rats or those treated with oestrogen alone. The simultaneous appearance of closure and endocytosis in response to the same physiological conditions is consistent with the proposal that the endocytotic activity in the uterine epithelial cells may remove fluid from the uterine lumen and thus mediate the first stage of uterine closure.

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