M Zygmunt

University of Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

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Publications (69)75.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The establishment of an appropriate fetomaternal vessel system is a prerequisite for prevention of pregnancy associated pathologies. Notch receptors and ligands are manifoldly involved in vascular development and angiogenesis. To further characterize the process of human placental vasculo- and angiogenesis we investigated the expression pattern of Notch receptors and their ligands during pregnancy. Real time RT-PCR, immunohistochemistry and flow cytometry analysis were performed in early (6-12) weeks of gestation (w.o.g.) and late placenta (37-41 w.o.g.). To specify the exact cellular localization immunofluorescent labelling of epithelial and endothelial cells (EC), respectively, with cytokeratin-7 and vonWillebrand factor (vWF) was done. One placenta from a patient with Alagille syndrome (AGS) was examined with real time RT-PCR and immunohistochemistry. The receptors Notch2, -3, -4 and their ligands Jagged1, -2 and Delta1, -4 were detected at both the mRNA and protein level in early and late placenta. Notch1 was only detected at protein level. The expression was found mainly in the stromal compartment: placental EC expressed Notch1, Delta4, Jagged1 and Delta1. A strong Jagged1 expression was found in the endothelium of arteries and veins supporting a role in differentiation of capillaries. Hofbauer cells (HC) primarily displayed the receptors Notch2, -3 and -4. Placental stromal cells (SC) were positive for Jagged2. The syncytiotrophoblast (ST) and cytotrophoblast (CT) cells revealed a weak but detectable co-localization with cytokeratin-7 and Notch1, -3 and Delta1. These results were verified by flow cytometry of freshly isolated placental cells of placental tissue. Interestingly Jagged1 expression was absent in endothelial cells from an AGS placenta. The Notch receptors and their ligands are expressed in human placental ST, CT, EC, SC and HC. The distribution pattern of Notch receptors and their ligands suggests their involvement in the process of placental vasculo- and angiogenesis via cell-cell communication between trophoblast, -stroma and endothelial cells.
    Placenta 08/2011; 32(8):554-63. · 3.12 Impact Factor
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    ABSTRACT: This prospective study aimed to compare sonoelastography, B-mode ultrasonography, and mammography in terms of their ability to distinguish benign from malignant breast lesions. We also assessed how the diagnostic value of sonoelastography differs between palpable and clinically occult lesions. Evaluation revealed a total of 97 lesions (66 benign; 31 malignant) without histological confirmation at the time of the initial examination. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) as well as efficiency were calculated. These parameters were separately assessed for palpable lesions and for non-palpable lesions. We subsequently compared these results. Sonography had a sensitivity of 97% and a specificity of 82% (PPV: 71 %, NPV: 98%, efficiency: 87%). For mammography, the respective figures were 84% and 89% (PPV: 79%, NPV: 92%, efficiency: 88%). Sonoelastography had a sensitivity of 71% and a specificity of 48% (PPV: 39%, NPV: 78%, efficiency: 56%). The combination of sonography and sonoelastography yielded a sensitivity of 100% and a specificity of 38% (PPV: 43%, NPV: 100%, efficiency: 58%). The sensitivity and specificity were not statistically different between the groups of palpable and non-palpable lesions. Sonoelastography is easily performed and not very time-consuming. Used by itself, the method is not more efficacious than alternative techniques. When used in conjunction with B-mode ultrasonography, the latter's sensitivity was increased, albeit at the expense of specificity.
    Ultraschall in der Medizin 12/2010; 31(6):596-603. · 4.12 Impact Factor
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    ABSTRACT: Both exogenous and endogenous factors during pregnancy may impact placental vascular development and cause different malformations of placental vessels. In humans, consequences of abnormal vascular development have been associated with different pregnancy-related pathologies ranging from miscarriage to intrauterine growth restriction or preeclampsia. Pregnancy-associated exposure to bacterial or viral infections or pharmacologic or toxic agents may also influence vascular development of the placenta and lead to preterm labor and delivery. Several steps of vascular adaptation on both the fetal and maternal side are necessary and include such events as uterine vasodilation, remodeling by extravillous trophoblast, as well as vasculogenesis and angiogenesis within the placenta. Ubiquitous as well as pregnancy-specific angiogenic factors are involved. Morphologic and stereologic approaches, as well as experiments in established laboratory animals, cannot be applied to large domestic animals or humans without hesitation. Thus, further studies into the different aspects of this process will require an appropriate in vitro model of placental vascular development. Reflecting the core of placental vascular development, the in vitro model should facilitate the interactions between trophoblast and stromal cells with endothelial progenitor cells. The effects of viral or bacterial infection as well as pharmacologic or toxic agents may be studied more closely in the process. This report reviews major aspects of vascular development in the placenta and describes the establishment of a three-dimensional in vitro model of human placental vascular development.
    Theriogenology 04/2010; 73(6):817-27. · 2.08 Impact Factor
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    ABSTRACT: The official birth statistics are regarded as a reliable data source on births and birth rate in the German population. However, they show methodological limitations with respect to the identification of first-time mothers and the number of children per mother. The mothers' social and economical background is not assessed. The goal of the present analysis was (a) to describe demographic and socio-economic variables of all births in a defined region over a fixed time-frame and (b) to make a comparison on the basis of parity and gravidity. From 2004-2007 4,982 children were born in the region and data from n=4,788 children were assessed (96%); n=3,505 (73%) of these mothers consented to a more detailed assessment. The fertility rate in the SniP region is low. There are fewer children per 1,000 women and born per women in general. The average age of primiparae was 25 and 26 years. As can be expected there is a significant difference between primiparae and multiparae with respect to age. There is also a difference in occupational status. 17% of the primiparae have been multigravidae. For the first time in Germany, the SNiP collected comprehensive population-based data on the age and socio-demographic variables of children and their mothers in a defined geographical region. A significant discrepancy for average age of primiparae between the study results and the official statistics is discussed in the light of methodological and regional issues. Our results require the continuation of comprehensive population-based data assessment. Furthermore, the SniP region could serve as a model region for future research. In international comparisons Germany's reproductive behaviour has proved to be unfavourable, which is accentuated in the region under examination.
    Zeitschrift für Geburtshilfe und Neonatologie 01/2010; 214(1):15-23. · 0.56 Impact Factor
  • Gesundheitswesen. 01/2010; 72.
  • Journal of Reproductive Immunology - J REPROD IMMUNOL. 01/2010; 86(1):61-61.
  • F Herr, N Baal, M Zygmunt
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    ABSTRACT: Undisturbed development and growth of the fetus depends on an adequate vascular development in the fetomaternal unit. Several steps of vascular adaptation both on fetal and maternal side are necessary and involve uterine vasodilation and remodelling by extravillous trophoblast as well as vasculo- and angiogenesis within the placenta. Ubiquitous (e. g. VEGF, bFGF) as well as pregnancy specific (PlGF, hCG, IGF-II, AFP) angiogenic factors are involved. Consequences of abnormal vascular development have been associated with different pregnancy-related pathologies ranging from miscarriage to intrauterine growth restriction or preeclampsia. Pregnancy-associated exposure to bacterial and viral infections or toxic agents (e. g. alcohol, nicotine or drugs) may also influence vascular development of the placenta and often lead to preterm labour and delivery. Different methods of study placental vascular development exist. Morphological and stereological approaches as well as animal models reveal significant limitations and can not be applied to in vivo human situation without hesitation. There is a need to design in vitro models of human placental vascular development allowing studies into the different aspects of this process including: trophoblast and stromal cells, interaction with endothelial progenitor cells, influence of viral or bacterial infection of trophoblast as well as influence of toxic agents. Our manuscript reviews major aspects of vascular development in the placenta and describes author's efforts to establish a three-dimensional model of this process in vitro.
    Zeitschrift für Geburtshilfe und Neonatologie 07/2009; 213(3):96-100. · 0.56 Impact Factor
  • Geburtshilfe Und Frauenheilkunde - GEBURTSH FRAUENHEILK. 01/2009; 69(09).
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    ABSTRACT: We aimed to illustrate the relationship between maternal obesity during pregnancy and maternal and fetal outcomes. We examined the influence of maternal BMI at the beginning of pregnancy on risks of pregnancy and birth, and on the somatic classification of the neonates. In our retrospective cohort study we included 499,267 singleton pregnancies taken from the German perinatal statistics of 1998-2000. 51,506 obese pregnant women (BMI >or= 30) were compared to 320,148 pregnant women of normal weight (BMI 18.50-24.99). We divided obesity into 3 BMI-categories: BMI = 30.00-34.99, BMI = 35.00-39.99, and BMI >or= 40.00. We defined small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), and large-for-gestational-age (LGA) status by birth weight percentiles. 10.3 % of all pregnant women had a BMI >or= 30.00 and 0.8 % had a BMI >or= 40.00. The frequency of hypertension increased with the extent of obesity: 7.1 % (BMI = 30.00-34.99), 12.5 % (BMI = 35.00-39.99) and 18.3 % (BMI >or= 40.00) compared to 1.2 % (BMI 18.50-24.99). Cephalopelvic disproportion was found in 6.8 % (BMI >or= 40.00) compared to 2.8 % (BMI 18.50-24.99). Fetal macrosomia occurred in 24.8 % (BMI >or= 40.00) compared to 7.9 % in the control group. Rates of pre-eclampsia, gestational diabetes, and fetal structural anomalies also increased with maternal BMI. Women with different BMIs differed in parity but not in age. Obesity during pregnancy is associated with a range of maternal and fetal adverse outcomes. Pregnancy in obese women therefore calls for close monitoring and careful planning of delivery. Pre-conceptional weight reduction should be considered.
    Zeitschrift für Geburtshilfe und Neonatologie 12/2008; 212(6):201-5. · 0.56 Impact Factor
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    ABSTRACT: The aim of this study was to analyse the age distribution of primiparous women and its influence on pregnancy and birth risks, presentation at birth and mode of delivery. We analysed the perinatal statistics of eight German federal states for the years 1998-2000. For our analysis we defined maternal age groups as follows: < 22, 22-32, > 32 years. We identified a total of 508,926 singleton pregnancies. 247,593 of these were delivered by primiparous women without preceding live or stillbirths. The mean age of the primiparas was 26.9 years. For older primiparas > 32 years the proportion with previous miscarriages and terminations of pregnancy was > 20 %. The risk of premature rupture of membranes, abnormal CTG and prolonged labour increased clearly with age. 91.0 % of women < 22 years and 84.5 % of women > 32 years had a normal cephalic presentation. Regarding the mode of delivery, 77.1 % (< 22 years) and 53.1 % (> 32 years) experienced spontaneous delivery, 14.5 % (< 22 years) and 32.3 % (> 32 years) had a Caesarean section. Older primiparas have a higher proportion of previous miscarriages and terminations of pregnancy. They more commonly experience pathological presentations and also more frequently require Caesarean section. This means that a delayed first pregnancy - an increasingly common phenomenon in Germany - goes along with an increased likelihood of birth risks, Caesarean sections and peripartal interventions. Older primiparous women constitute a special risk group which may require a more intense level of care.
    Zeitschrift für Geburtshilfe und Neonatologie 12/2008; 212(6):206-10. · 0.56 Impact Factor
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    ABSTRACT: Placental vascular development matches fetal growth and development. Quantification of the feto-placental vasculature in placentas from pregnancies is complicated by intrauterine growth restriction (IUGR) revealed confounding results. Therefore, the feto-placental vascular volume in IUGR placentas was assessed by 3D micro-computed tomography (micro-CT). Placental probes from IUGR (n=24) and healthy control placentas (n=40) were perfused in situ with Microfil or BaSO(4) and randomly chosen samples were scanned by micro-CT. Using 3D images, we quantitated the feto-placental vascular volume fraction (VVF). A subanalysis was performed at three different levels, reaching from the chorionic plate artery (level A), to intermediate arteries (level B) and capillary system (level C). Results were complemented by histology. The significance of differences in vascular volume measurements was tested with analysis of variance [ANOVA]. Microfil perfused placentas showed a total vascular volume fraction of 20.5+/-0.9% in healthy controls. In contrast, the VVF decreased to 7.9+/-0.9% (p<0.001) in IUGR placentas. Significant differences were found between Microfil and BaSO(4) perfused placentas in the vascular volume fraction using micro-CT and histology. Micro-CT demonstrated localized concentric luminal encroachments in the intermediate arteries in placentas complicated by IUGR. Micro-CT imaging is feasible for quantitative analysis of the feto-placental vascular tree in healthy controls and pregnancies complicated by IUGR.
    Placenta 10/2008; 29(11):937-41. · 3.12 Impact Factor
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    ABSTRACT: Natural-orifice transluminal endoscopic surgery (NOTES) is regarded as safer and less invasive than laparoscopic surgery. However, there has been no documentation of the opinions of surgically active, experienced gynecologists about the indications, contraindications, risks, and complications of transvaginal access. A two-page questionnaire was distributed to the heads of the gynecological departments at 181 university and major teaching hospitals across Germany, Austria, and Switzerland. Fifty-two questionnaires (28.7 %) were returned and evaluated. The questionnaire contained ten questions, four of which were yes/no questions and another five of which allowed between four and seven answers. The questionnaire contained one additional open question. Of the respondents, 69.2 % classified transvaginal access for extrapelvic abdominal surgery as ethical; the remaining 30.8 % described it as experimental. Only 28.8 % would recommend NOTES to their patients if NOTES presented the same surgical risks as the laparoscopic approach. When asked about NOTES-associated complications, 73.1 % mentioned the risk of infection, 61.5 % visceral lesions, 44.2 % infertility, and 34.6 % adhesions. In terms of long-term problems, gynecologists are concerned about dyspareunia and infertility. Adopting their patients' point of view, 17.3 % voted the lack of scarring compared to laparoscopy as important and 57.6 % as unimportant. While transvaginal NOTES is argued to be a promising access for scarless surgery, gynecologists mention postoperative infection, visceral lesions, infertility, and adhesions as conceivable complications. Since long-term experience has not yet been achieved, potential problems such as dyspareunia, infertility, and the spread of pre-existing endometriosis remain definitely conceivable complications.
    Endoscopy 08/2008; 40(7):576-80. · 5.74 Impact Factor
  • Geburtshilfe Und Frauenheilkunde - GEBURTSH FRAUENHEILK. 01/2008; 68(08):794-800.
  • Rofo-fortschritte Auf Dem Gebiet Der Rontgenstrahlen Und Der Bildgebenden Verfahren - ROFO-FORTSCHR RONTGENSTRAHL. 01/2008; 180.
  • Ultraschall in Der Medizin - ULTRASCHALL MED. 01/2008; 29.
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    ABSTRACT: The gonadotropins, whose members are human chorionic gonadotropin (hCG), lutenizing hormone (LH) and follicle-stimulating hormone (FSH) are a well characterized hormone family known to regulate reproductive functions in both females and males. Recent studies indicate that they can modulate the vascular system of reproductive organs. It was shown that gonadotropins not only influence the expression of vascular endothelial growth factor (VEGF) and both its receptors VEGFR-1 and -2, but also modulate other ubiquitously expressed angiogenic factors like the angiopoietins and their receptor Tie-2, basic fibroblast growth factor or placental-derived growth factor. Some recent data indicates a possible direct action of gonadotropins on endothelial cells. Thus, the gonadotropins act as tissue-specific angiogenic factors providing an optimal vascular supply during the menstrual cycle and early pregnancy in the female reproductive tract as well as in testis. In pathological conditions (e.g. preeclampsia, intrauterine growth restriction, ovarian hyperstimulation or endometriosis), these tightly regulated interactions between the gonadotropins and the ubiquitous angiogenic factors appear to be disturbed. The intent of this short manuscript is to review the current knowledge of the regulatory role of the gonadotropins in vasculo- and angiogenesis. We also review angiogenic actions of thyroid-stimulating hormone (TSH), a glycoprotein closely related to gonadotropins, which display strong gonodal actions.
    Molecular and Cellular Endocrinology 05/2007; 269(1-2):65-80. · 4.04 Impact Factor
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    ABSTRACT: Placental vascular development is essential for fetal growth and development. Inadequate placental vascular development is associated with early pregnancy losses and other pregnancy related pathologies. In addition to the ubiquitous, well-characterized angiogenic factors like vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), some pregnancy-specific factors (e.g. human chorionic gonadotropin (hCG), insulin-like growth factor-II (IGF-II) or alpha fetoprotein (AFP) were recently described to play a possible regulatory role in this process. In the present study we described an improved separation method for human placental microvascular endothelial cells (HPMVEC) and their functional characterization. Using the combination of enzymatic digestion and multistep immunomagnetic sorting with CD31 antibodies a model for villous vascularization was established. Isolated cells took up ac-dil-LDL, spontaneously formed capillary-like structures, and expressed common endothelial markers such as vascular endothelial growth factor receptor-2 (VEGFR-2), angiopoetin-1 and -2, Tie-2, CD144, thrombomodulin, and von Willebrand factor (vWF) as shown by RT-PCR, flow cytometry and Western blot analysis. The expression of the hCG/LH receptor in the placental vascular tree was verified both in vitro and in vivo. hCG stimulated proliferation of HPMVEC in a dose specific manner. While hCG alone had no significant effect on endothelial cell apoptosis, the combination of VEGF-A and hCG protected HPMVEC from staurosporine-induced apoptosis. hCG significantly stimulated sprout formation when compared to controls in a spheroid angiogenesis assay. Our results demonstrate a modified and reproducible method allowing studies of placental vascular development and provide new insights into the possible role of trophoblastic factors in this process.
    Placenta 05/2007; 28 Suppl A:S85-93. · 3.12 Impact Factor
  • Ultraschall in Der Medizin - ULTRASCHALL MED. 01/2007; 28.
  • Zeitschrift Fur Geburtshilfe Und Neonatologie - Z GEBURTSH NEONATOLOGIE. 01/2007; 211.
  • Ultraschall in Der Medizin - ULTRASCHALL MED. 01/2007; 28.

Publication Stats

406 Citations
75.40 Total Impact Points

Institutions

  • 2007–2011
    • University of Greifswald
      • Department of Obstetrics and Gynecology
      Greifswald, Mecklenburg-Vorpommern, Germany
  • 1997–2008
    • Justus-Liebig-Universität Gießen
      • Department of Obstetrics and Gynaecology
      Gießen, Hesse, Germany
  • 2005
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 2004
    • Universitätsklinikum Gießen und Marburg
      Marburg, Hesse, Germany
  • 2000–2001
    • Philipps University of Marburg
      Marburg, Hesse, Germany