Objective To compare the assessment of endometrial maturation parameters in endometrial secretion samples obtained by a novel minimally invasive technique with those assessed in tissue biopsies.Design Prospective study.Setting University Hospital.Population Healthy female volunteers attending a gynaecological outpatient clinic.Methods Endometrial secretion fluid and tissue sampling 5 days after a spontaneous ovulation assessed with ultrasound.Main outcome measures Progesterone (P) receptor, Ki‐67 expression and the Noyes criteria were used to date endometrial biopsies. In the endometrial fluid samples, glycodelin A (GdA), leukaemia inhibitory factor (LIF) and P levels were analysed, and protein content and electrophoresis patterns were determined.Results All data were correlated to estradiol (E2) and P serum concentrations. The dating according to histology and immunohistochemical staining patterns correlated significantly with GdA levels (r = 0.376, P =0.048) in endometrial fluid samples as well with serum levels of E2 (r = 0.568, P =0.001) and P (r = 0.408, P =0.023). No correlation was observed between tissue dating and LIF levels and protein content in endometrial fluid samples.Conclusions The measurement of GdA in endometrial secretion samples may provide a less invasive method for assessing endometrial maturation in potential conception cycles without disrupting implantation.

The objective of this study was to investigate the effect of ovarian stimulation for IVF on endometrial secretion and tissue markers of receptivity in the mid-luteal phase. In 10 oocyte donors, endometrial secretions and biopsies were sampled 5 days after spontaneous ovulation and oocyte retrieval in consecutive cycles. Four subjects received progesterone in the luteal phase of the stimulated cycles. Mid-luteal endometrial maturation in the stimulated cycle was compared with the spontaneous cycle, by histological dating, Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) expression, secretion levels of leukaemia inhibitory factor (LIF), glycodelin A (GdA) and progesterone, and protein profile. No significant differences in histological markers, expression of Ki-67, PR, ER, secretion protein profiles or concentrations of LIF, GdA, or progesterone were observed when comparing natural with stimulated cycles. Progesterone supplementation of stimulated cycles was associated with significantly lower Ki-67 (P = 0.03) and ER (P = 0.04) expression compared with the non-supplemented stimulated cycle. In this pilot study, ovarian stimulation was not demonstrated to alter the studied markers of endometrial maturation in the mid-luteal phase.

Einleitung: Bei der Intrauteringravidität (IUG) können maternale immunkompetente T-Zellen mittels Apoptoseinduktion die Trophoblastinvasion begrenzen. In der Dezidua von Patientinnen mit Spontanaborten fand sich eine erhöhte Anzahl von CD3+ T-Zellen. Bei der Tubargravidität sind Tubaraborte im Gegensatz zu vitalen Tubargraviditäten durch eine 7-fach erhöhte Zahl an immunkompetenten CD3+CD8+ T-Zellen gekennzeichnet, die apoptoseinduzierende Mediatoren wie z.B. TNFalpha sezernieren können.

The semi-allogeneic fetus has to be tolerated by the maternal immune system. In mice, it has been shown that inhibiting indoleamine-dioxygenase (IDO) leads to fetal rejection, suggesting a central significance for IDO in establishing maternal tolerance. Consequently, we have analyzed IDO expression in human endometrium and decidua to determine whether it may be of significance in human reproduction. Endometrial (n = 60) and decidual (n = 68; first and second trimester) tissue samples and isolated cells were analyzed for IDO mRNA and protein expression by real-time PCR, Western blot and immunohistochemistry. IDO expression in the decidua of proven fertile women (n = 34) was compared to women presenting with their first pregnancy (n = 22) and women with a history of miscarriages (n = 12). Expression of IDO was localized in glandular epithelial cells and scattered stromal leukocytes. Expression started at the mid-luteal phase in the menstrual cycle and was high until the second trimester of pregnancy. However, glandular expression of IDO decreased during the second trimester, whereas expression in villous trophoblast started at this time. There were no significant differences in decidual IDO expression between proven fertile women and women presenting with their first pregnancy or women with a history of miscarriages. From the expression pattern we conclude that IDO may play a central role in human pregnancies for the establishment of maternal tolerance of fetal antigens. Thereby, IDO expression may be needed in each pregnancy independently from prior pregnancies, and a history of miscarriage may not reflect a general deficiency in IDO expression.

Annals of the New York Academy of SciencesVolume 923, Issue 1 p. 348-354 Uteroglobin/Clara Cell 10-kDa Family of Proteins: Nomenclature Committee Report J. KLUG, Corresponding Author J. KLUG Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, D-35033 Marburg, Germanya Address for correspondence: J. Klug, Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Emil-Mannkopff-Strasse 2, D-35033 Marburg, Germany. Voice: +49 6421 28 66545; fax: +49 6421 28 65398. Klug@IMT.Uni-Marburg.deSearch for more papers by this authorH. M. BEIER, H. M. BEIER Department of Anatomy and Reproductive Biology, RWTH University of Aachen, D-52057 Aachen, GermanySearch for more papers by this authorA. BERNARD, A. BERNARD Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Catholic University of Louvain, B-1200 Bruxelles, BelgiumSearch for more papers by this authorB. S. CHILTON, B. S. CHILTON Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USASearch for more papers by this authorT. P. FLEMING, T. P. FLEMING Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USASearch for more papers by this authorR. I. LEHRER, R. I. LEHRER Department of Medicine and Molecular Biology Institute, University of California (Los Angeles) School of Medicine, Los Angeles, California 90095-1690, USASearch for more papers by this authorL. MIELE, L. MIELE Cardinal Bernardin Cancer Center and Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USASearch for more papers by this authorN. PATTABIRAMAN, N. PATTABIRAMAN Advanced Biomedical Computing Center, SAIC-NCI/FCRDC, Frederick, Maryland 21702-1201, USASearch for more papers by this authorG. SINGH, G. SINGH Department of Pathology, University of Pittsburgh School of Medicine and VA Medical Center, Pittsburgh, Pennsylvania 15240, USASearch for more papers by this author J. KLUG, Corresponding Author J. KLUG Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, D-35033 Marburg, Germanya Address for correspondence: J. Klug, Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Emil-Mannkopff-Strasse 2, D-35033 Marburg, Germany. Voice: +49 6421 28 66545; fax: +49 6421 28 65398. Klug@IMT.Uni-Marburg.deSearch for more papers by this authorH. M. BEIER, H. M. BEIER Department of Anatomy and Reproductive Biology, RWTH University of Aachen, D-52057 Aachen, GermanySearch for more papers by this authorA. BERNARD, A. BERNARD Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Catholic University of Louvain, B-1200 Bruxelles, BelgiumSearch for more papers by this authorB. S. CHILTON, B. S. CHILTON Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USASearch for more papers by this authorT. P. FLEMING, T. P. FLEMING Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USASearch for more papers by this authorR. I. LEHRER, R. I. LEHRER Department of Medicine and Molecular Biology Institute, University of California (Los Angeles) School of Medicine, Los Angeles, California 90095-1690, USASearch for more papers by this authorL. MIELE, L. MIELE Cardinal Bernardin Cancer Center and Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USASearch for more papers by this authorN. PATTABIRAMAN, N. PATTABIRAMAN Advanced Biomedical Computing Center, SAIC-NCI/FCRDC, Frederick, Maryland 21702-1201, USASearch for more papers by this authorG. SINGH, G. SINGH Department of Pathology, University of Pittsburgh School of Medicine and VA Medical Center, Pittsburgh, Pennsylvania 15240, USASearch for more papers by this author First published: 25 January 2006 https://doi.org/10.1111/j.1749-6632.2000.tb05549.xCitations: 84Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume923, Issue1THE UTEROGLOBIN/CLARA CELL PROTEIN FAMILYDecember 2000Pages 348-354 RelatedInformation

Many mammary tumors express estrogen receptors (ER) and progesterone receptors (PR), and there is increasing evidence that progestins influence gene expression of breast tumor cells. To analyse the impact of progestins on breast cancer cells, we compared (a) the expression of two cytokines, involved in tumor progression, and searched (b) for differentially regulated genes by a microarray, containing 2400 genes, on T47D breast cancer cells cultured for 6 days with 17beta-estradiol (E2) or E2+medroxyprogesterone acetate (E2+MPA). Lower amounts of PDGF and TNFalpha were found in culture supernatants of E2+MPA treated T47D cells. MPA addition induced a 2.8-3.5-fold increase of the mRNA expression of (a) tristetraprolin, which is involved in the posttranscriptional regulation of cytokine biosynthesis, and (b) zinc-alpha2-glycoprotein and Na, K-ATPase alpha1-subunit, which both resemble differentiation markers of breast epithelium. In contrast, the mRNA expression of lipocalin 2, which promotes matrixmetalloproteinase-9 activity, was decreased five-fold in E2+MPA treated cells. Our data show that the expression of genes from various functional gene families is regulated differentially by E2 and E2+MPA treatment in T47D cells. This suggests that exogenous progestins applied for therapy and endogenous changes of the progesterone levels during the menstrual cycle both influence breast cancer pathophysiology.

m die Jahreswende 2004/2005 fullten sich die Wis-senschaftsseiten der Tageszeitungen ebenso wie die„Klatschspalten“ der renommiertesten wissenschaftli-chen Journale, insbesondere Science und Nature, mitAuseinandersetzungen und Kommentaren uber aktuelleTrends in der Forschung mit menschlichen embryonalenStammzellen (ES-Zellen). Selbst unsere Parlamentarierliesen das Jahr 2004 nicht ruhig im Bundestag ziehen,sondern debattierten, ohne jegliche neuen Argumente inder Sache, dieses Mal nicht uber Stammzellforschung inDeutschland, sondern uber das erstaunliche Ergebnis derSchweizerischen Volksabstimmung zur embryonalenStammzellforschung (Dt. Bundestag 15/145, 2.12.2004).Mit uberwaltigender Mehrheit hatten die Schweizer Bur-ger entschieden, das in ihrem Land mit menschlichenembryonalen Stammzellen geforscht werden darf, unddies ausdrucklich auch mit ES-Zell-Linien, die aus ver-waisten Blastozysten aus der Reproduktionsmedizin, sog.uberzahligen Embryonen, in der Schweiz hergestellt wer-den. Groste Verwunderung auch in der Frankfurter Allge-meinen Zeitung, zur besonderen Uberraschung sogar inder Rubrik „Politik“: „Zuletzt haben die Schweizer, einschwer entflammbares, christlich gepragtes Volk, zu66 Prozent ja gesagt. Sogar in den konservativen Kanto-nen gab es Mehrheiten fur die Embryonennutzung.“ [1]Unbeeindruckt von europaischen und US-amerikani-schen ethischen Problemen und gesetzlichen Hemmnis-sen, humane ES-Zell-Linien zu etablieren oder mit ihnenzu forschen, findet in den asiatischen Landern Sudkorea,Singapur, Taiwan und China ein beispielloser Wettlaufum die wissenschaftliche Fuhrung in dieser Forschungstatt [2]. Die Schwerpunktinvestitionen fur ES-Zell-For-schung umfassen in diesen Landern ein Vielfaches der-jenigen in den USA und Europa. Die unbeschreiblicheAufbruchstimmung wird am besten durch ein Beispielmodernen „Forschernomadentums“ charakterisiert. Dieamerikanische Forschungsstiftung JDRF (Juvenile Diabe-tes Research Foundation) unterstutzt seit 2002 den spani-schen ES-Zell-Forscher Bernat Soria mit einem Grant von600.000 US$, damit er in Singapur seine Arbeiten mithumanen ES-Zellen fortsetzen kann. In Spanien warendiese in den Jahren 2002 und 2003 nicht erlaubt. Ob-

Uteroglobin (UG) is a conserved protein which is induced by progesterone and secreted by the epithelia of various mammalian reproductive and respiratory organs. Recombinant bovine uteroglobin (recbUG), consisting of 80 amino acids with a C-terminal His6 tag, was overexpressed in Escherichia coli and purified. The protein was crystallized in two geometric forms, rhomboid and cuneate (wedge-shaped), by the hanging-drop vapour-diffusion method at 295 K. The rhomboid crystals diffracted to a maximum resolution of 1.6 A using synchrotron radiation. These crystals belong to space group P2(1)2(1)2, with unit-cell parameters a = 81.42, b = 82.82, c = 45.26 A, and contain four monomers per asymmetric unit. The cuneate crystals diffracted to 2.35 A resolution using a rotating-anode generator. These crystals belong to space group C222(1), with unit-cell parameters a = 43.39, b = 93.94, c = 77.30 A, and contain two molecules per asymmetric unit.

Die Tubargravidität (TG) wird häufig als Modell für die Plazentation bei der Intrauteringravidität (IUG) angesehen. Wir haben daher Trophoblastinvasion und mögliche maternale Begrenzungsreaktion bei TG und IUG untersucht.

Reversible histone acetylation has been identified as major regulator of eukaryotic gene transcription: the removal of acetyl-groups from the amino-terminal end of core histones catalysed by histone deacetylases (HDACs) induces gene repression. Recently, it has been shown that inhibition of histone deacetylation enhances progesterone-induced decidualisation of human endometrial stroma cells. Furthermore, histone deacetylase inhibitors induced differentiation in breast cancer cells.

The morphological characteristics and percentage of the cellular associations between gonadotrophs (LH- and FSH-secreting cells) and other cellular types were studied in pituitary pars distalis of adult male viscachas (Lagostomus maximus maximus) by double immunohistochemistry using specific antibodies to LH, FSH, PRL, GH, ACTH, TSH and S-100 protein (by folliculostellate cells; FSC), during long and short photoperiods. Bihormonal gonadotrophs were observed in ventro-medial and dorsal regions, interspersed between monohormonal gonadotrophs, and their number increased in short photoperiod. LH- and FSH-gonadotrophs were found around lactotrophs, enclosed by somatotrophs in the dorsal region, and associated with irregular corticotrophs. Gonadotrophs and thyrotrophs were associated along blood vessels and follicular structures. The cytoplasmic prolongations of FSC were in contact with both gonadotrophs. The percentage of LH–FSH, LH–ACTH, LH–FSC, FSH–LH, FSH–PRL, FSH–GH, FSH–ACTH, FSH–TSH and FSH–FSC associations decreased, whereas LH–PRL increased in short as compared to long photoperiod. The most abundant associations were LH–GH and LH–TSH during long photoperiod, but LH–GH and LH–PRL during short photoperiod. FSH–GH and FSH–PRL were the most numerous associations, and LH–FSC and FSH–FSC were the less abundant ones in both photoperiods. These results provide the morphological evidence for specific cellular associations between gonadotrophs and other cellular types of viscacha pituitary.

Background: Evidence is emerging that haptoglobin, an acute phase protein with immunomodulatory properties, is expressed by the endometrium of various species. The present study describes an in-depth investigation of haptoglobin expression and release in the rabbit reproductive tract and in preimplantation embryos. Methods: The full-length cDNA sequence of rabbit haptoglobin was determined by rapid amplification of cDNA ends PCR. Haptoglobin expression was studied in the oviductal ampull, and isthmus, endometrium and embryos from the time of ovulation up to adhesion. These results were completed by western blot analysis of reproductive tract secretions and embryonic tissues. Results: cDNA sequencing showed a high homology between rabbit and human haptoglobin (84.1%). In oviductal tissues haptoglobin mRNA is clearly expressed from 6 h post-conception (p.c.) to day 3, and in the uterus on days 5 and 6. In the oviductal fluid highest haptoglobin protein content was found between 6 h p.c and day 2, and in the uterine fluid on days 5 and 6 p.c. Embryos do not express haptoglobin mRNA during preimplantation development. However, considerable amounts of maternal haptoglobin protein were detected in the blastocyst coverings and in blastocyst fluid. Conclusions: Already during periovulatory time and oviductal passage, high amounts of haptoglobin are present in the microenvironment surrounding the oocyte/embryo. Two days before implantation, again, high haptoglobin levels are detectable in the embryo's environment. The incorporation of haptoglobin into the extra-embryonic matrix may be of particular functional significance.

Embryo implantation and subsequent decidualization, trophoblast invasion and formation of a functional placenta are crucial for establishment and maintenance of pregnancy. Interleukin-11 signalling has been shown to be obligatory for adequate decidualization and trophoblast invasion in mice. Defects in IL-11 signalling in mice result in trophoblast over-invasion and fetal loss. The pathological situation of human tubal pregnancy resembles that of IL-11Ralpha(-/-) mice concerning these symptoms. As our interest is focused on the human early pregnancy, we compared IL-11 expression at the implantation site of ectopic tubal pregnancy (EP) to 1st and 2nd trimester of normal intrauterine pregnancies (IP), and to the normal cycling endometrium. The mRNA expression of IL-11 and IL-11Ralpha was analysed by semiquantitative RT-PCR. Protein expression was detected by western blotting and immunohistochemistry. IL-11Ralpha is expressed constitutively in all tissue specimens analysed. IL-11 is expressed predominantly during follicular and early luteal phase of the menstrual cycle. In IP, IL-11 expression peaks during the 1st trimester and declines from the beginning of the 2nd trimester onwards. In tubal abortions, IL-11 expression is reduced in comparison to vital EP and IP. Cultured primary endometrial and decidual epithelial cells were analysed for hormonal regulation of IL-11 by enzyme-linked immunosorbent assay and RT-PCR. IL-11 is up-regulated by estrogen and down-regulated by progesterone. Overall, our results indicate that in humans, IL-11 signalling is significantly involved in regulation of trophoblast invasion. In the case of tubal abortion, inadequate IL-11 signalling may therefore result in dysregulation of trophoblast invasion.

The transmembrane protein gp130 plays a central role in cytokine action as a signal transducing receptor subunit common to all interleukin-6 type cytokines. Endometrial tissue obtained from women with a normal menstrual cycle and decidua obtained from women in the first or second trimester of pregnancy were assessed for gp130 by western blotting, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analysis. By immunoblotting, two forms of gp130 were detected: one-the soluble form-of approximately 100 kDa and a larger membrane-bound form of approximately 150 kDa. The latter became clearly visible in the mid to late secretory phase and was more pronounced in decidual tissue of second trimester compared to first trimester. Immunohistochemically, gp130 was located in glandular epithelial cells during the mid to late secretory phase, whereas staining in the proliferative phase was rather weak. In first and second trimester decidua, glandular cells were also positively stained. In addition, the invading trophoblast cells were gp130 positive. Soluble gp130 release was measured in the supernatants from primary endometrial and decidual cell cultures by ELISA and reached maximum values in cell cultures without addition of hormones. In cultured endometrial epithelial cells obtained during the proliferative phase of the cycle, the soluble gp130 release increased significantly under combined estradiol/progesterone supplementation which mimics the secretory phase conditions compared to estradiol supplementation alone. In cultured epithelial cells derived from decidual tissue of first trimester of pregnancy, similar effects of hormonal regulation were observed. Our results suggest that the balance between soluble gp130 and its membrane-bound form may play an important role in regulating cytokine action necessary for blastocyst implantation and for further interaction between the decidualized endometrium and the invading trophoblast.

Aus Anlass der Veröffentlichung des ersten Tätigkeitsberichts der Zentralen Ethik-Kommission beim Robert-Koch-Institut werden aktuelle Aspekte zur Forschung mit embryonalen Stammzellen in Deutschland berichtet. Insbesondere werden die mit weltweiter Aufmerksamkeit verfolgten neuesten Befunde über die Differenzierung von embryonalen Stammzellen der Maus zu Spermien und Eizellen dargestellt. Diese Befunde geben erneut Diskussionsanstöße, über den Status der embryonalen Stammzellen mit Blick auf die deutsche Gesetzeslage nachzudenken. Die wissenschaftliche Diskussion zeigt indessen, dass eine Änderung der wissenschaftlichen Einschätzung, dass alle embryonalen Stammzellen pluripotent sind, keiner Revision bedarf. Die sprachliche und terminologische Klarheit wird erneut als wesentlicher Beitrag für jede ethische und rechtliche Beurteilung angesehen. Die öffentliche Debatte sollte verantwortungsvoller Forschung Raum geben, um künftige ethische und rechtliche Entscheidungen auf dem Boden gesicherten Wissens zu treffen.

Objective: To compare cytokine expression profiles of decidua basalis (containing trophoblast cells) and decidua parietalis (without trophoblast cells) for determination of microenvironments in human first trimester decidua.Design: Retrospective study.Setting: School of Medicine, RWTH University of Aachen, Aachen Germany, and Bourgognekliniek Maastricht, Maastricht, The Netherlands.Patient(s): Forty-six women who had undergone elective first-trimester termination of viable pregnancy at 5 to 12 weeks.Main Outcome Measure(s): Quantitative cytokine protein analysis in decidual tissues by enzyme-linked immunosorbent assay, qualitative cytokine messenger (m)RNA analysis in isolated decidual cell samples, and comparative mRNA and protein analysis in tissues of decidua basalis compared with decidua parietalis.Result(s): Interleukin-2, interferon-gamma (Th-1). interleukin-4 (Th-2), and interleukin-1beta proteins are expressed in the human first-trimester decidua. Interleukin-2, interferon-gamma, and interleukin-4 mRNA mainly derive from the decidual tissue leukocytes. Interleukin-1beta mRNA is expressed by all decidual cell types. Interferon-gamma mRNA and protein is detected predominantly in the decidua basalis, which contains trophoblast cells.Conclusion(s): Microenvironments are established topographically by different expression of cytolkines in decidua basalis and decidua parietalis. These locally specific patterns are indicative of fetomaternal cross-talk. Higher interferon-gamma concentrations in decidua basalis may influence leukocyte differentiation (e.g., macrophage activation) and trophoblast invasion (e.g., by induction of expression of major histocompatibility complex). (C) 2003 by American Society for Reproductive Medicine.