bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen Regulation of Lactoferrin Expression in Human Endometrium
Authors: Kelver Mae Ellen , Kaul Anil , Nowicki Bogdan , Findley William E. , Hutchens T. William , Nagamani Manubai 
Published: September 2011

PROBLEM: Lactoferrin is an iron‐binding glycoprotein that has been shown to be overexpressed in human endometrial carcinomas. The purpose of our present study is to investigate the possible role of estradiol in the expression of lactoferrin.METHOD OF STUDY: We investigated 1) serum levels of lactoferrin in five women during normal ovulatory cycles, 2) serum levels of lactoferrin during ten human menopausal gonadotropin induced cycles when estradiol levels are high, and 3) lactoferrin expression in five proliferative and five secretory phase endometrium by immunohistochemical studies. The serum concentrations of lactoferrin were measured by a peroxidase‐based enzyme‐linked immunosorbent assay.RESULTS: In normal ovulatory cycles, the mean serum lactoferrin concentration during the proliferative phase (0.4013 ± 0.0242 μg/mL) was significantly higher (P<0.02) than in the secretory phase (0.3468 ± 0.0209 μg/mL). In induced cycles, there was gradual increase in lactoferrin levels with increasing estradiol concentrations. Peak lactoferrin levels in induced cycles (0.7495 ± 0.1148 μg/mL) were significantly higher (P<0.003) than the midcycle levels (0.423 ± 0.0424 μg/mL) in normal cycles. Immunohistochemical analysis of the endometrium revealed greater expression of lactoferrin in proliferative endometrium (50.7 ± 13%, range 28–72%) than in secretory endometrium (19.2 ± 4%, range 7–31%).CONCLUSION: These results indicate that estradiol may play a role in the regulation of lactoferrin expression in human endometrium.
Induction and Postranslational Expression of G‐CSF and RANTES in a First Trimester Trophoblast Cell Line by Lipopolysaccharide
Authors: Svinarich David M. , Bitonti Ornella M. , Araneda Hereberto , Romero Roberto , Gonik Bernard 
Published: September 2011

PROBLEM: Comparatively little is known about the capacity of first trimester trophoblasts to respond to an infection and coordinate an immune response. This study characterizes the LPS induction of G‐CSF and RANTES in a first trimester trophoblast cell line.METHODS: HTR‐8/SVneo cells were exposed to LPS (1 μg/ml) for 0, 2, 4, 6, 8, and 24 hours in DMEM‐Ham's F‐12 media supplemented with 10% fetal bovine serum. Cytokine levels in culture supernatants were measured by ELISA. Northern analysis of total RNA was conducted using antisense cytokine probes.RESULTS: Levels of immunoreactive G‐CSF and RANTES from LPS induced cultures at 24 hours were 10‐fold and 8.5‐fold greater than cytokine levels from non‐induced cells at 24 hours, respectively (P<0.01). Under LPS induction, maximal rates of G‐CSF and RANTES transcription occurred at 24 hours and 8 hours, respectively.CONCLUSION: The LPS induction of proinflammatory cytokines in a first trimester trophoblast cell line supports the contention that first trimester trophoblasts participate in cytokine based immune signaling in response to infection.
Regulation of Cultured Human Chorion Cell Chemokine Production by Group B Streptococci and Purified Bacterial Products
Authors: Dudley Donald J. , Edwin Samuel S. , Dangerfield Albina , Waggoner Jennifer Van , Mitchell Murray D. 
Published: September 2011

PROBLEM: To determine if different strains of group B streptococci (GBS) and purified bacterial products regulate chemokine production by cultured human chorion cells.METHOD OF STUDY: Primary cultures of human chorion cells were established from placentae isolated from normal women at term gestation having repeat cesarean section. Five different strains of heat‐killed GBS were incubated with confluent chorion cells at 107 bacteria/ml for 16 hours at 37°C. In separate experiments, lipoteichoic acid and sialic acid at various concentrations were incubated with chorion cells for 16 hours at 37°C. Culture supernatants were collected and then assayed to determine concentrations of interleukin‐8 (IL‐8) and macrophage inflammatory protein‐1α (MIP‐1α) by ELISA.RESULTS: We found that GBS stimulated chorion cell production of MIP‐1α in a strain‐specific fashion. We also found that both lipoteichoic acid and sialic acid stimulated concentration‐dependent increases in chorion cell IL‐8 production. Chorion cells, however, did not increase MIP‐1α production in response to either lipoteichoic acid or sialic acid. Two strains of GBS tested induced concentration‐dependent increases in both IL‐8 and MIP‐1α, but both stimulated IL‐8 production to a greater extent. Similarly, IL‐1β also caused chorion cells to produce more IL‐8 than MIP‐1α.CONCLUSIONS: Our data are the first to show that GBS and purified bacterial products can stimulate chemokine production by fetal gestational tissues. We suggest that chorion cells may produce specific types of chemokines to attract different types of inflammatory cells and thus may participate in the pathophysiology of infection‐mediated preterm labor by directing specific inflammatory responses.
Monoclonal Antibodies Reacting Against Capacitated but not With Freshly Ejaculated Boar Spermatozoa
Authors: Mollova Margarita V. , Atanasova Galina A. , Kyurkchiev Stanimir , Ivanova Maria D. , Peknicova Jana 
Published: September 2011

PROBLEM: The involvement of individual sperm proteins in differentiation of antigenically specific and functionally defined regions on sperm membrane has not yet been completely elucidated.METHOD: BALB/c mice were immunized with live capacitated boar spermatozoa and used for production of monoclonal antibodies (MAbs). ELISA, IIF, SDS‐PAGE, IVF, and cytologic methods were used for selection and biological characterization of MAbs as well as for identification of corresponding antigens.RESULTS: MAb1F10, MAb2E2, and MAb4B12 react with antigens in the acrosome portion of live capacitated spermatozoa. MAb 1F10 reacted with human sperm cells along with those from bull, ram, mouse, dog, whereas MAb2E2—with mouse's spermatozoa and MAB4B12 ‐ with bull's, mouse's, and dog's spermatozoa. Some glycolytic enzymes seemed to reduce mildly the reactions of the MAbs with enzyme treated sperm cells; proteolytic enzymes eliminated the binding of MAbs to the sperm acrosome. These MAbs have no sperm agglutinating and/or sperm‐immobilizing activities and reduced the number of spermatozoa binding to zona pellucida.CONCLUSIONS: MAb1F10, MAb2E2, and MAb4B12 seemed to recognize membrane associated antigens with potential role in the initial stages of fertilization, specific for capacitated but not for freshly ejaculated spermatozoa.
Altered Expression of Human Leukocyte Antigen G (HLA‐G) on Extravillous Trophoblasts in Preeclampsia: Immunohistological Demonstration With Anti‐HLA‐G Specific Antibody “87G” and Anti‐cytokeratin Antibody “CAM5.2”
Authors: Hara Naonori , Fujii Tomoyuki , Yamashita Takahiro , Kozuma Shiro , Okai Takashi , Taketani Yuji 
Published: September 2011

PROBLEM: Human leukocyte antigen‐G (HLA‐G) is suggested to be at play in the materno‐fetal immune relationship during pregnancy. In the light of current concept that disruption of the materno‐fetal immune relationship could account for several complications of pregnancy, including preeclampsia, we asked whether the expression of HLA‐G protein on the trophoblasts is altered in preeclampsia.METHOD: The presence of HLA‐G protein in the extravillous trophoblasts in placenta obtained from five preeclamptic patients and seven uncomplicated pregnant women was determined by means of an immunohistochemical technique.RESULTS: All of the extravillous trophoblasts, which were stained for cytokeratin, were stained for HLA‐G protein in every woman with an uncomplicated pregnancy. In contrast, clusters of extravillous trophoblasts were insularly devoid of the staining for HLA‐G in all the preeclamptic patients.CONCLUSION: The attenuated expression of HLA‐G protein on the extravillous trophoblasts could be at play in the pathophysiology of preeclampsia.
The Immunological Pregnancy Protective Effect of Progesterone Is Manifested via Controlling Cytokine Production
Authors: Szekeres‐Bartho Julia , Faust Zs. , Varga P. , Szereday L. , Kelemen K. 
Published: September 2011

PROBLEM: This study was aimed at investigating the involvement of an altered cytokine pattern in the immunomodulatory and anti‐abortive effects of a progesterone‐induced immunomodulatory protein (PIBF).METHOD: PIBF expression on lymphocytes of healthy pregnant women and from women at risk for premature pregnancy termination was determined. In sera of the same women TNFα was quantified by a bioassay using L929 cells. NK activity was determined by a single cell cytotoxicity assay. Cytokine production of the lymphocytes or murine spleen cells was measured by ELISA or detected by immunocytochemistry. In pregnant mice endogenous PIBF activity was neutralized by anti‐PIBF IgG.RESULTS: Sera of women at risk for premature pregnancy termination contained significantly higher concentrations of TNFα than those from healthy pregnant women and PIBF expression on the lymphocytes was inversely related to serum concentration of TNFα. Increased NK activity of lymphocytes after neutralization of endogenous PIBF activity is corrected by anti‐IL2 treatment and PIBF inhibits IL12 expression on activated lymphocytes. PIBF increases IL‐10 production by activated spleen cells. In pregnant mice, neutralization of endogenous PIBF activity by specific antibody results in increased resorption rate and reduced splenic IL‐10 production.CONCLUSIONS: Our data allow the assumption that via blocking IL‐12 production PIBF inhibits NK activation with a concomitant reduction of TNFα levels. Disturbances in this system might lead to the expression of the known synergistic effect of IL‐12 and TNFα, resulting in a Th1 type cytokine dominance and pregnancy termination.
Elevated Peripheral Blood Natural Killer Cells Are Effectively Downregulated by Immunoglobulin G Infusion in Women With Recurrent Spontaneous Abortions
Authors: Kwak J.Y.H. , Kwak F.M.Y. , Ainbinder S.W. , Ruiz A.M. , Beer A.E. 
Published: September 2011

PROBLEM: We investigated the hypothesis that elevated peripheral blood natural killer cells (NK) are decreased by immunoglobulin G infusion (IVIg) therapy in women with recurrent spontaneous abortions (RSA) and elevated NK cells.METHODS: Seventy‐three women with RSA and elevated NK cells received IVIg therapy (400 mg/Kg/day for 3 days ever 4 wks) and anticoagulation treatment. Peripheral blood immunophenotype assay by flow cytometry was done prospectively prior to and 7 days after first IVIg therapy, every 2 wks until 20 wks gestation and then monthly. Controls were 95 women with RSA and normal NK cells who received anticoagulation treatment.RESULTS: (1) 86.3% of women with elevated NK cells who received the IVIg and anticoagulation therapy had a successful pregnancy outcome; (2) Peripheral blood CD56+ NK cells and CD56+/16+ NK cells were significantly suppressed 7 days post IVIg infusion (P < 0.0005); (3) Pre‐IVIg infusion levels of other lymphocyte subsets were not different as compared with those of 7 days post‐IVIg therapy; (4) Women who delivered a liveborn infant with IVIg therapy demonstrated downregulation of peripheral blood NK cells (CD56+, CD56+/16+) during early pregnancy when compared to women who miscarried the index pregnancy (P < 0.05); (5) Women with normal NK cells who miscarried while on anticoagulation therapy demonstrated significantly elevated CD56+ NK cells during early pregnancy as compared with that of women who delivered a liveborn infant (P < 0.05); (6) CD19+ B cells were significantly downregulated during pregnancy in women with anticoagulation and IVIg therapy when compared to women with anticoagulation therapy (P < 0.05).CONCLUSION: Downregulation of NK cells in women with RSA is associated with a favorable pregnancy outcome. Peripheral blood NK cells (CD56+, CD56+/16+) are effectively suppressed after IVIg therapy. Women with RSA and high NK cells benefit from IVIg therapy and experience suppression of CD56+ and CD56+/16+ NK cells.
Cervical Mucus Anti‐Sperm Antibodies: Treatment With Intrauterine Insemination
Authors: Kutteh William H. , Byrd William , Blankenship Linda , Kutteh Carol C. , Carr Bruce R. 
Published: September 2011

PROBLEM: To determine (1) the incidence of cervical mucus anti‐sperm antibodies in infertile women, and (2) the results of treatment by intrauterine insemination.METHOD: Cervical mucus was collected the morning after urinary LH surge occurred from 153 consecutive women being treated for unexplained infertility with intrauterine insemination. Immunobead testing for IgG, IgA, IgA1, and IgA2 was performed with only actively motile sperm being counted.RESULTS: Overall, 23/153 (15.0%) of cervical mucus samples were positive for anti‐sperm antibodies: 9/23 (39.1%) were only IgA‐positive (62% IgA1‐positive, 38% IgA2‐positive), 11/23 (47.8%) were only IgG‐positive, and 3/23 (13.0%) were positive for both IgA and IgG. Insemination resulted in a pregnancy in 6/23 (26.1%) of women with cervical mucus anti‐sperm antibodies after 1–3 cycles.CONCLUSIONS: Testing for cervical mucus anti‐sperm antibodies should be performed in cases of “unexplained” infertility, and intrauterine insemination may be an effective treatment, resulting in pregnancies in over one‐fourth of couples.
Genetic Factors in Reproduction and Their Evolutionary Significance
Authors: Gill Thomas J. 
Published: September 2011

PROBLEM: The reproductive process is a major driving force in human evolution. An evolutionary perspective was brought to bear on some aspects of reproduction and its aberrations, and, conversely, some of the insights of modern reproductive genetics were used to investigate problems in evolution.METHOD: The data used were obtained from the literature in evolution, anthropology, archeology, linguistics, and genetics.RESULTS: The evolutionary line leading to modern humans diverged from that leading to the chimpanzees approximately 5–7 million years ago (Mya). Archaic Homo sapiens emerged ca. 0.3 Mya, and modern Homo sapiens and the development of language ca. 0.1 Mya; thus, modern humans occupy approximately 2% of the evolutionary history of the hominid line. During all of this time, the ancestors of modern humans were migratory hunter‐gatherers. It was only during the Neolithic transition ca. 0.01 Mya (approximately 0.2% of of hominid evolutionary history) that agriculture was developed, and with it a settled lifestyle that allowed a more stable existence and the development of a different reproductive pattern. Various estimates indicate that the human population increased from 0.05 million at the time of the emergence of modern Homo sapiens to 6,000 million at the present time (120,000‐fold increase).CONCLUSIONS: These evolutionary considerations were used to explore three areas: (1) the extinction of the Neanderthals, who coexisted for ca. 65,000 years with modern humans; (2) the relatively low and stable rate of human conceptions (20–35% of ova fertilized naturally or fertilized in vitro); and (3) the long postnatal period required for the full maturation of the immune response. From these considerations, a broad view of the human reproductive process was obtained that may provide some insight into the rationale for the development of effective reproductive technologies.
Lymphocyte Immunotherapy (LI) Increases Serum Levels of Progesterone Induced Blocking Factor (PIBF)
Authors: Check Jerome H. , Arwitz Maria , Gross Jenifer , Peymer Mark , Szekeres‐Bartho Julia 
Published: September 2011

PROBLEM: To determine if allogenic stimulation from leukocyte immunization (LI) can increase the production of an immunomodulatory protein called progesterone induced blocking factor (PIBF) by CD8+ T‐lymphocytes.METHOD: The study group consisted of 35 women, 29 who failed to conceive after repeated embryo transfers (ETs) and six with recurrent spontaneous abortion (RSA). The women underwent LI using the male partner's blood as the source of leukocytes. Progesterone induced blocking factor was measured pre‐ and post‐LI with an immunocytochemistry method using a PIBF‐specific polyclonal antibody.RESULTS: The mean percentage of lymphocytes expressing PIBF, as well as the percentage of cases whose PIBF level increased to 1% or more, was significantly higher post‐LI. Similarly post‐LI, there was a significantly lower percentage of zero PIBF levels.CONCLUSIONS: Leukocyte immunization causes an increase in PIBF in many cases. Possibly the improved pregnancy outcome in immunized patients with RSA or previous failure to conceive with in vitro fertilization may be partially or possibly completely explained by its stimulatory effect on PIBF.
The Implications of a Paternally Derived Centrosome During Human Fertilization: Consequences for Reproduction and the Treatment of Male Factor Infertility
Authors: Navara Christopher S. , Hewitson Laura C. , Simerly Calvin R. , Sutovsky Peter , Schatten Gerald 
Published: September 2011

PROBLEM: Successful fertilization in humans follows a complex series of events, including the completion of meiotic maturation of the oocyte with the extrusion of the second polar body, the decondensation of the sperm nucleus and the maternal chromosomes into male and female pronuclei, the restoration of the sperm centrosome, and the nucleation of microtubule‐mediated motility necessary to bring the male and female pronuclei into close apposition. These events occur after both fertilization in vitro and after intracytoplasmic sperm injection (ICSI), a new technique which is currently being applied in many clinics to overcome severe male infertility. Defects in any of the events leading to fertilization can be lethal to the zygote and may prove to be causes of infertility.METHODS: Imaging of inseminated human and rhesus oocytes using immunohistochemical techniques reveals several phases at which fertilization arrests.RESULTS: Oocytes from some infertile patients failed to complete fertilization due to failure of the sperm aster microtubules in uniting the sperm and egg nuclei. The rate of sperm aster formation, size, and organization during fertilization has been used as a measurement of bovine sperm quality. The development of an assay using Xenopus laevis oocyte extract can also be used to test sperm from various species for their ability to form asters and perform other centrosomal functions in vitro, as well as another indicator of sperm quality. Semen from men with questionable fertility was found to contain sperm which are generally incapable of producing sperm asters. In addition, the activity of centrosomal proteins such as γ‐tubulin and centrin have been detected in mammalian eggs and sperm. The levels of γ‐tubulin increase markedly after exposure to X. laevis egg extract.CONCLUSION: Defects in either male or female nucleus decondensation also resulted in the arrest of fertilization and was found to occur in both inseminated human oocytes and in rhesus oocytes fertilized by ICSI. These discoveries on the molecular basis of infertility in humans have important implications for infertility diagnosis and managing reproduction.
Review: Cytokine Involvement in Ovarian Processes
Authors: Terranova P.F. , Rice V. Montgomery 
Published: September 2011

PROBLEM: Expression of tumor necrosis factor‐α (TNF) and interleukins 1α and 1β (IL‐1) have been reported in ovaries of several species and humans and are implicated in ovarian follicular development and atresia, ovulation, steroidogenesis, and corpus luteum function (including formation, development, and regression). The principal abnormal processes affected by these cytokines are ovarian cancer and reduction of ovarian function during sepsis.METHODS: A literature review.RESULTS: Numerous studies indicate that TNF and IL‐1 inhibit gonadotropin‐stimulated steroidogenesis of undifferentiated ovarian cells due to inhibition of adenylyl cyclase and post‐cAMP sites. In differentiated ovarian cells, these cytokines either stimulate progesterone synthesis or have little to no effect on steroidogenesis. Both cytokines participate in ovulation and levels of these cytokines increase during the periovulatory period. Endotoxin inhibits gonadotropin‐stimulated ovarian steroidogenesis and follicular development and these effects are mediated, in part, by TNF and by direct effects of endotoxin on ovarian cells. In newly formed corpora lutea, progesterone secretion is inhibited by TNF and IL‐1, although each has proliferative effects. TNF also has been implicated in regression of corpora lutea because TNF stimulates prostaglandin synthesis and luteal TNF increases after initiation of the decline in progesterone secretion. TNF and IL‐1 are secreted by some ovarian cancer cells and stimulate growth of these cells.CONCLUSIONS: Thus, TNF and IL‐1 are multifunctional factors affecting various ovarian processes.
Stress Triggered Abortions Are Associated With Alterations of Granulated Cells in the Decidua
Authors: Markert Udo R. , Arck Petra C. , McBey Betty Ann , Manuel Justin , Croy B. Anne , Marshall Jean S. , Chaouat Gerard , Clark David A. 
Published: September 2011

PROBLEM: Stress is known to be abortogenic in animals and humans. An increased decidual release of cytokines such as TNF‐α and reduction in TGF‐β2‐related immunosuppressive activity has been proposed as the triggering mechanism. Substance P released by nerves in endometrium/decidua has been found to be the key neurotransmitter in this pathway. It is still unclear which cells are stimulated by substance P to produce the increased TNF‐α level.METHOD: As a measure of local activation, the granulation of granulated metrial gland (GMG) cells was measured by flow cytometry after sonic plus immobilization stress of mice or substance P treatment of GMG cells (both isolated GMG cells and GMG‐cell containing decidua). TNF‐α release from decidua and isolated GMG cells was investigated using a TNF‐α bioassay. The degranulation of uterine mast cell, another potential source of TNF‐α, was examined in situ by Toluidine blue staining.RESULTS: We observed a striking increase in percentage of degranulated mast cells (8% r̊ 24%) in the uteri of stressed animals, whereas the granularity of GMG cells was decreased by stress but increased with treatment with substance P in vitro. Isolated GMG cells appeared to release in vitro cytotoxins active in the TNF‐α bioassay, but the magnitude of this activity was not increased by stress or by substance P treatment. In contrast, disaggregated decidual tissue which is known to release increased amounts of TNF‐α after stress, did increase activity in response to substance P in vitro.CONCLUSIONS: Uterine mast cells show activation as reflected by degranulation after stress exposure of pregnant mice and mast cells might be the cellular link between the neurotransmitter substance P and an increase in decidual TNF‐α release that leads to abortion.