bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukemia Inhibitory Factor in Human Reproduction
Authors: Senturk Levent M. , Arici Aydin 
Published: September 2011

PROBLEM: Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin‐6 family and has different biological actions in various tissue systems. Although named for its ability to inhibit proliferation of a myeloid leukemic cell line by inducing differentiation, it also regulates the growth and differentiation of embryonic stem cells, primordial germ cells, peripheral neurons, osteoblasts, adipocytes, and endothelial cells. LIF is crucial for successful implantation of the embryo in mice. Currently, there is an accumulation of data about the role of LIF in human reproduction.METHOD OF STUDY: This review of the literature and of our studies focuses on the expression, regulation, and effects of LIF in the human endometrium, fallopian tube, and ovarian follicle.RESULTS: Human endometrium expresses LIF in a menstrual cycle‐dependent manner. Maximal expression is observed between days 19 and 25 of the menstrual cycle, coinciding with the time of implantation. Various cytokines and growth factors induce endometrial LIF expression in vitro. LIF receptor is expressed in endometrial tissue throughout the menstrual cycle and on human blastocysts in a stage‐dependent manner. Affecting the trophoblast differentiation pathway toward the adhesive phenotype, LIF plays a role in implantation. LIF is also expressed and secreted by the epithelial cells of the fallopian tube. Its increased expression in the tubal stromal cell cultures by the inflammatory cytokines suggests a link between salpingitis and ectopic implantation in the tube. The rising follicular fluid LIF level around the time of ovulation indicates that LIF may play a role in ovulatory events, early embryonic development, and implantation.CONCLUSIONS: There is growing evidence that LIF may be one of the entities that plays a role in human reproduction.
Preliminary Studies with Recombinant Chorionic Gonadotropin β‐Subunit Produced in Escherichia coli for Use as an Antigen in a Birth Control Vaccine
Authors: Mukhopadhyay Asok , Bhatia Prakish K. , Majumdar Subeer S. 
Published: September 2011

PROBLEM: Prototype human chorionic gonadotropin (hCG) vaccines based on natural sources are unsuitable for widespread applications due to their complex manufacturing procedures, cost, and carrier‐mediated immune suppression.METHOD OF STUDY: Wistar rats were immunized with alum‐adsorbed CGβ (recombinant), CGβ‐TT, and nCGβ (native CGβ)‐TT, whereas Bonnet monkeys were immunized with only CGβ. The anti‐hCG antibody titre in the sera obtained at different time points were quantified by radioimmunoassay. The sera of Wistar rats were characterized in terms of their affinity to hCG, bioneutralization capacity (by inhibition of hCG‐induced testosterone production in Leydig cells), and cross‐reactivity with human luteinizing hormone, human follicle‐stimulating hormone, and human thyroid‐stimulating hormone (by direct binding assays).RESULTS: Antigen‐binding capacities of sera obtained upon immunization with CGβ were 3,080 ± 943 ng/ml (n = 6) and 3,993 ± 1,292 ng/ml (n = 4), respectively, in rats and monkeys. The analysis of data revealed that immunization of rats with CGβ produced antibodies comparable to that of CGβ‐TT and nCGβ‐TT.CONCLUSION: The study opens up the possibility of producing pure and highly immunogenic CGβ by a recombinant DNA route, as a consistent source of antigen for birth control vaccine.
Experimental Autoimmune Prostatitis: In Vivo Induction of the Autoimmune Response to Lymphocytic Soluble Factors. Alterations at the Endocrine Metabolism Level
Authors: Diserio Gustavo P. , Nowotny Edgar 
Published: September 2011

PROBLEM: In rats, immunization with male accessory gland (MAG) extract promotes experimental autoimmune vesicle prostatitis. A specific mononuclear cell‐mediated immune response and prostate androgen metabolism impairment in MAG‐immunized rats were observed. The possibility that lymphocytic soluble factors (SoFs) can regulate the local steroid metabolism in these rats directly was studied. We investigated whether the SoFs released by MAG‐sensitized lymphocytes are capable of modifying the prostatic androgen metabolism and whether they induce histologic lesions “in vivo” when they are inoculated, carried by liposomes, into untreated rats.METHOD OF STUDY: “In vitro” enzymatic [3H]‐5α‐dihydrotestosterone bioconversion and histologic studies were performed with prostates from SoF‐treated rats (LK rats). The obtained 3α/β‐hydroxysteroid‐oxidoreductase activities showed that LK rat values were significantly lower than in controls: 79.0 ± 2.5 vs 158.7 ± 10.2 pmol/min/mg protein, respectively (P < 0.01).RESULTS: In the histologic studies, LK rat prostates showed focalized mononuclear infiltrates of various degrees, whereas control rats showed non‐atypic modification of the gland.CONCLUSION: These results indicate that SoFs (probably total lymphokines) contribute significantly to the pathogenesis of experimental autoimmune prostatitis, involving a biochemical relationship between immune reaction and the androgenic enzymatic inhibition in the prostate.
Effects of Antibodies to Transferrin and Alpha 2‐HS Glycoprotein on In Vitro Sperm Motion: Implications in Infertility Associated with Endometriosis
Authors: Pillai Subbi , Rust Philip F. , Howard Leslie 
Published: September 2011

PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and alpha 2‐HS glycoprotein in their serum and peritoneal fluid. The objective of this study was to determine whether antibodies to transferrin and alpha 2‐HS glycoprotein adversely affect sperm motility and survival.METHOD OF STUDY: Spermatozoa obtained from normal fertile donors and washed free of seminal plasma were incubated with the medium (control), 1:2 and 1:100 dilutions of antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti‐alpha 2‐HS glycoprotein, and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion characteristics in 10 μl aliquots were evaluated at 30 min, 1 hr, 2 hr, 4 hr, and 24 hr using computerized sperm motion analysis. A paired t‐test was done to analyze the effects of the various antibodies on sperm motion characteristics.RESULTS: Antibodies to albumin failed to adversely affect sperm motility in general or the several sperm motion characteristics in particular. In contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the percentage of motile and rapid spermatozoa, progressive and path velocities, straightness, linearity, track speed, and anterior‐lateral head displacement (P < 0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum adversely affected these parameters only at 24 hr. Elongation and beat cross‐frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of antitransferrin antiserum. The effects of anti‐alpha 2‐HS glycoprotein were more pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4 and 1:8 were effective at all time intervals, whereas a 1:100 dilution was effective in reducing the track speed and the percentage of rapid cells at 24 hr (P < 0.001).CONCLUSION: Antibodies to endometrial transferrin and alpha 2‐HS glycoprotein present in the peritoneal fluid, and possibly in the oviductal fluid, of patients with endometriosis may adversely affect postcoital sperm motility and sperm survival.
Increased Numbers of Circulating Interferon‐γ‐and Interleukin‐4‐Secreting Cells During Normal Pregnancy
Authors: Matthiesen Leif , Berg Göran , Ekerfelt Christina , Ernerudh Jan , Ernerudh Jan 
Published: September 2011

PROBLEM: Systemic immune responses during normal pregnancy are suggested to deviate toward secretion of T helper (Th)2‐like cytokines.METHOD OF STUDY: Blood samples from 11 healthy Primigravidae in their first, second, and third trimesters, and 8 weeks postpartum were examined. Peripheral blood mononuclear cells were separated and the numbers of interferon (IFN)‐γ‐ and interleukin (IL)‐4‐secreting cells were identified by using the enzyme‐linked immunospot test.RESULTS: In all three trimesters of pregnancy, and also postpartum, the numbers of IFN‐γ‐and IL‐4‐secreting cells were significantly higher compared with nonpregnant controls (Mann‐Whitney; P < 0.001). The numbers of IFN‐γ‐and IL‐4‐secreting cells gradually increased as the pregnancy progressed compared with postpartum (Kruskas‐Wallis; P < 0.01 and P < 0.05, for IFN‐γ and IL‐4, respectively).The ratios of IFN‐γ/IL‐4 during pregnancy and postpartum were unchanged, and also when compared with nonpregnant controls.CONCLUSION: The results indicate a systemic up‐regulation of both Th1‐ and Th2‐like immune responses during normal pregnancy.
Hepatocyte Growth Factor in Human Breast Milk
Authors: Yamada Yoshihiko , Saito Shigeru , Morikawa Hajime 
Published: September 2011

PROBLEM: The purposes of this study were to investigate the presence of hepatocyte growth factor (HGF) in human milk, to identify the cells that produce HGF in human milk, and to determine the contribution of HGF to the growth of neonates.METHOD OF STUDY: The HGF concentrations in serum and whey were determined with an enzyme‐linked immunosorbent assay kit. The presence of HGF in whey was also examined by Western blot analysis. To determine which cells in human milk produce HGF, an immunohistochemical examination was conducted. The expression of HGF mRNA in the mononuclear cells in human milk was examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR). The effects of whey and of recombinant HGF (rHGF) on DNA synthesis by a rat small intestinal cell line, IEC‐6, were examined by [3H]thymidine uptake.RESULTS: Human colostrum whey contained 2.22 ± 1.02 ng of HGF/ml. Milk whey collected 1 month later contained 1.83 ± 1.03 ng of HGF/ml. The presence of the heterodimeric form of HGF in colostrum whey was demonstrated by Western blot analysis. HGF was detected in the cytoplasm of human milk macrophages by an immunohistochemical examination, and the RT‐PCR also revealed that HGF mRNA is expressed in the mononuclear cells of human milk. DNA synthesis by IEC‐6 cells was increased by rHGF treatment and by whey treatment. The effect of whey on DNA synthesis by IEC‐6 cells was partially, but significantly, decreased by anti‐human HGF‐neutralizing antibody treatment.CONCLUSIONS: Human milk contains a large amount of the active form of HGF, produced by macrophages, and HGF in human milk induces the growth of intestinal cells. Our data suggest that HGF in human milk is one of the important factors regulating the growth of intestinal cells in neonates after birth.
Molecular and Immunologic Aspects of the Nonclassical HLA Class I Antigen HLA‐G: Evidence for an Important Role in the Maternal Tolerance of the Fetal Allograft
Authors: MOREAU PHILIPPE , PAUL PASCALE , ROUAS‐FREISS NATHALIE , KIRSZENBAUM MAREK , DAUSSET JEAN , CAROSELLA EDGARDO D. 
Published: September 2011

PROBLEM: Human leukocyte antigen (HLA)‐G is a major histocompatibility complex class I antigen, which is referred to as nonclassical because it displays a tissue‐restricted distribution in the placenta, a reduced cytoplasmic domain, a limited polymorphism, and several isoforms. The HLA‐G antigen is thought to play an essential role during pregnancy by protecting the semi‐allogeneic fetus from recognition and destruction by maternal immune cells.METHOD OF STUDY: Alternative splicing of HLA‐G mRNA was analyzed by Southern blot of reverse transcriptase‐polymerase chain reaction products from trophoblasts of the first trimester of gestation and term placenta. The regulation of HLA‐G gene expression was investigated by electrophoretic mobility shift assays using nuclear extracts from cells expressing different levels of HLA‐G gene activity. Using polymerase chain reaction‐single strand conformational polymorphism and sequencing, we studied HLA‐G gene polymorphism in families from the Centre d'Etude du Polymorphisme Humain in Paris. To understand the function of the HLA‐G molecule, cytotoxicity assays were carried out with peripheral blood mononuclear cells or polyclonal natural killer effectors cells from 30 different donors against HLA‐G1 and HLA‐G2 transfectants.RESULTS: Four main aspects have been elucidated: 1) The primary transcript of the HLA‐G gene is alternatively spliced into five main mRNA forms: HLA‐G1 (full length), HLA‐G2 (minus exon 3), which encodes a membrane‐bound isoform associated with beta‐2 microglobulin, HLA‐G3 (minus exons 3 and 4), HLA‐G4 (minus exon 4), and HLA‐G5 (plus intron 4), which encodes a soluble form of the HLA‐G antigen; 2) specific nuclear factors bind to an important regulatory element located more than 1.2 kb from the HLA‐G gene. Three specific complexes are observed in cells that show HLA‐G transcriptional activity and an additional factor that could correlate with the repression of HLA‐G gene expression that is detected in natural killer cells; 3) we observed an important genomic polymorphism in exon 3 but a very low polymorphism at the protein level; 4) HLA‐G1 and HLA‐G2 transfectants clearly demonstrated that both HLA‐G isoforms are capable of inhibiting natural killer lytic activity.CONCLUSION: These results suggest that HLA‐G acts as the public ligand for natural killer inhibitory receptors, thus protecting the fetus against maternal rejection.
Regulation of Major Histocompatibility Complex and TAP Gene Products in Preimplantation Mouse Stage Embryos
Authors: COOPER J. C. , FERNANDEZ N. , JOLY E. , DEALTRY G. B. 
Published: September 2011

PROBLEM: To determine the ontogeny of major histocompatibility complex (MHC) expression and TAP products in mouse embryos.METHOD OF STUDY: mRNAs encoding MHC and associated molecules were identified by reverse transcriptase‐polymerase chain reaction, and the protein products were localized by confocal microscopy.RESULTS: mRNAs encoding class Ia (H‐2Db) and class Ib (Q7/9) were present in one‐cell embryos, whereas β2‐microglobulin (β2‐m) transcripts were not detected until the two‐cell stage. Transporter TAP1, but not TAP2, transcripts were detected only in blastocysts. H‐2 class Ia (classical) protein was detected on the surface of two‐cell embryos, H‐2 class Ib (nonclassical) protein was detected on one‐cell embryos, and β2‐m transcripts were detected on eight‐cell embryos; TAP1 protein was present at low levels in the cytoplasm from the one‐cell stage onward, increasing in expression in blastocysts.CONCLUSIONS: In mice, MHC class I mRNAs encoding the heavy chain of H‐2‐ and Q7/9‐encoding Qa2 molecules are synthesized soon after conception prior to implantation. Similarly, the nonpolymorphic MHC class I‐associated molecule β2‐m also is expressed before implantation. TAP1, but not TAP2, is first detected at the blastocyst stage, thus preceding the onset of TAP2 in embryonic development.
Analysis of Human Leukocyte Antigen‐G Polymorphism Including Intron 4 in Japanese Couples with Habitual Abortion
Authors: Yamashita Takahiro , Fujii Tomoyuki , Tokunaga Katsushi , Tadokoro Kenji , Hamai Yoko , Miki Akinori , Kozuma Shiro , Juji Takeo , Taketani Yuji 
Published: September 2011

PROBLEM: The purpose of this study was to clarify whether there is a difference between the allele frequency of human leukocyte antigen (HLA)‐G in healthy Japanese people and that of Japanese couples with habitual abortion.METHOD OF STUDY: Exons 2, 3, 4, and intron 4 of the HLA‐G gene were analyzed in 20 couples with habitual abortion, using polymerase chain reaction (PCR)‐single‐strand conformation polymorphism (SSCP) analysis. Intron 4 of the HLA‐G gene was also analyzed in 54 healthy individuals. The nucleotide sequence of the PCR product of intron 4 was further determined by direct sequencing.RESULTS: Two kinds of nucleotide sequence were identified in intron 4 of the HLA‐G gene, one of which was identical to that of HLA‐G*01011, and the other was identical to that of HLA‐G*01012, G*01013, and G*0104. The frequency of each allele in affected women and their husbands did not significantly differ from that of healthy individuals, and no mutation was found in any affected couple.CONCLUSION: HLA‐G allelic abnormality seemed to have little, if any, implication in the pathogenesis of habitual abortion.
The Effect of Nitric Oxide on Sperm Cell Function and Embryo Development
Authors: Joo Bo Sun , Park Sea Hee , Park Sue Jin , Kang Ho Sung , Moon Hwa Sook , Kim Han Do 
Published: September 2011

Joo BS, Park SH, Park SJ, Kang HS, Moon HS, Kim HD. The effect of nitric oxide on sperm cell function and embryo development. AJRI 1999; 42:327–334 © Munksgaard, CopenhagenPROBLEM; Nitric oxide (NO) has been known to have multifunctional roles both in the male and female reproductive systems. We investigated the effects of sodium nitroprusside (SNP)‐dependent NO release on sperm cell function and embryo development to elucidate the mechanisms of action of NO.METHOD OF STUDY: Semen samples from 20 healthy men were processed by the swim‐up method. Sperm motility, hyperactivation, and acrosome reaction were examined following incubation with various concentrations of SNP. The concentration of 10 nM to 1 mM was used for sperm motility and hyperactivation measurement and 1 μM to 1 mM for examining the effect on acrosome reaction. Embryo development to blastocyst stage was assessed using 100 nM to 1 mM of SNP added before transferring the mouse embryos into the culture medium. Finally, to understand the mechanism of action of NO, changes in embryo development were examined after zygotes were treated with various concentrations ranging up to 1 mM of 8‐bromo‐cGMP, an analog of cGMP.RESULTS: Both sperm motility and hyperactivation were significantly reduced at 100 μM and 1 mM concentrations of SNP after 6 hr of incubation. After 24 hr of incubation, they were greatly decreased with all, except the 10 nM concentration of SNP. The percentage of acrosomal‐reacted spermatozoa was increased with the increasing concentration of SNP following incubation with 10 μM and 1 mM of SNP. Embryo development was arrested since the two‐cell embryonic stage with all except the 100 nM concentration of SNP, and inhibited by 200 μM of SNP regardless of SNP treatment stage. However, embryo development was not influenced by 8‐bromo‐cGMP.CONCLUSIONS: We concluded that SNP‐inhibited sperm cell function and embryo development in a dose‐ and time‐dependent manner, and the inhibitory effect on embryo development, may not be a stage‐specific treatment mediated via a cGMP‐independent pathway. This result suggests that NO may be enough to affect the fecundity potential in vivo.
Spontaneous and Induced Release of Prostaglandins, Interleukin (IL)‐1β, IL‐6, and Tumor Necrosis Factor‐α by Placental Tissue from Normal and Preeclamptic Pregnancies
Authors: Munno Irene , Chiechi Luigi M. , Lacedra Giuseppe , Putignano Giuseppe , Patimo Caterina , Lobascio Anna , Loizzi Pasquale 
Published: September 2011

Munno I, Chiechi LM, Lacedra G, Putignano G, Patimo C, Lobascio A, Loizzi P. Spontaneous and induced release of prostaglandins, interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α by placental tissue from normal and preeclamptic pregnancies. AJRI 1999; 42:369–374 © Munksgaard, CopenhagenPROBLEM: The objective of this study was to clarify the role of the main proinflammatory cytokines (interleukin [IL]‐1, IL‐6, tumor necrosis factor [TNF]‐α) in the pathogenesis of preeclampsia and how these cytokines affect one another and the production of prostaglandins (PGs).METHOD OF STUDY: The concentrations of cytokines and PGs in supernatants of placental tissue from preeclamptic and normal women were determined by enzyme‐linked immunosorbent assay.RESULTS: The concentrations of the PGs from unstimulated preeclamptic placental tissue were significantly higher compared to the concentrations of PGs from normal unstimulated placental tissue. Significant levels of IL‐1β were observed only in the supernatants of preeclamptic placental tissue. Of interest, an increase in TNF‐α production was detected in the supernatants of IL‐1‐stimulated preeclamptic placental tissue.CONCLUSIONS: The overproduction of TNF‐α may be related not only to the effect of a stimulant like IL‐1β, but mainly to the lack of mechanisms down‐regulating the production of TNF‐α.
Interleukin‐8 Stimulates Placental Prostacyclin Production in Preeclampsia
Authors: Wang Yuping , Baier John , Adair C. David , Lewis David F. , Krueger Stephan , Kruger Tom , Gurski Michael , Brown Edwin 
Published: September 2011

Wang Y, Baier J, Adair CD, Lewis DF, Krueger S, Kruger T, Gurski M, Brown E. Interleukin‐8 stimulates placental prostacyclin production in preeclampsia. AJRI 1999; 42:375–380 © Munksgaard, CopenhagenPROBLEM: Our purpose was to determine placental interleukin (IL)‐8 production and its correlation with the prostacyclin production in normal and preeclamptic pregnancies and to evaluate the beneficial effect of IL‐8 on prostacyclin production.METHOD OF STUDY: We determined 1) the in vitro production of IL‐8 and prostacyclin by placental villous tissues from normal and preeclamptic pregnancies and 2) the production of prostacyclin by villous tissues from preeclampsia treated with recombinant human IL‐8 (rhIL‐8). IL‐8 levels were measured by enzyme‐linked immunosorbent assay and prostacyclin by radioimmunoassay of 6‐keto PGF1α, the stable metabolite of prostacyclin.RESULTS: 1) Placental production of IL‐8 and 6‐keto PGF1α were significantly less in preeclampsia than in normal pregnancies, P < 0.05. 2) Placental production of 6‐keto PGF1α and IL‐8 was significantly correlated in preeclampsia, P < 0.01. 3) Placental tissues treated with IL‐8 exhibited a concentration‐dependent increase in 6‐keto PGF1α production.CONCLUSIONS: Placental tissues from preeclampsia produce significantly less IL‐8 than tissues from normal pregnancies, which correlates with decreased prostacyclin production. IL‐8 improves placental prostacyclin production in preeclampsia.
Human Decidualized Endometrial T Lymphocytes Do Not Substantially Down‐Regulate CD3ζ
Authors: Bedenicki Ivica , Newton Darren J. , Flanagan Brian F. , Johnson Peter M. , Rukavina Daniel , Christmas Dr. Stephen E. 
Published: September 2011

PROBLEM: The T‐cell antigen receptor (TCR) has been reported to be down‐regulated on T‐cells in the decidualized endometrium in early pregnancy.METHOD OF STUDY: The expression of CD3ζ, a component of the TCR complex, has been investigated in human first‐trimester decidual T‐cells using flow cytometric analysis of permeabilized cells.RESULTS: Levels of CD3ζ expression were significantly lower in decidual than in peripheral T‐cells from non‐pregnant women, as assessed by mean fluorescence intensity (4.2 vs. 5.5. logarithmic scale, P < 0.05). However, when decidual and peripheral T‐cells from the same subjects were analyzed (n = 10), mean levels of CD3ζ were slightly, but not significantly, lower in decidual than in peripheral T‐cells (P > 0.1). CD3ζ was not substantially down‐regulated systemically as mean cytoplasmic CD3ζ levels did not differ significantly between peripheral blood T‐cells from pregnant women and non‐pregnant controls (P > 0.2). CD8+ cells outnumber CD4+ cells in decidua, but neither the proportions of these two T‐cell subsets positive for cytoplasmic CD3ζ nor the mean levels of CD3ζ were significantly different.CONCLUSIONS: These results indicate that human decidual T‐cells do not greatly down‐regulate CD3ζ, but it is unclear if a small decrease in mean levels may be sufficient to compromise their capacity for activation.