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  • 1. Liu, Y X
    et al.
    Hu, Z Y
    Liu, K
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Byrne, S
    Zou, R J
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    d'Lacey, C
    Ockleford, C D
    Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes1998In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 19, no 2-3, 171-180 p.Article in journal (Refereed)
    Abstract [en]

    Fetal membranes consist of 10 distinct layers including components of amnion, chorion and decidua, the latter being of maternal origin. They form mechanically integrated sheets capable of retaining amniotic fluid and play an essential role in protecting fetal growth and development in the pregnant uterus. The extracellular matrix, substrate for plasminogen activators (PAs), is an important supportive framework of the fetal membranes. Fetal membranes from women with preterm premature rupture of membranes may differ in their protease activity compared with normal membranes. To identify the presence of PAs and their inhibitors (PAI) and their possible role in the process of fetal membrane rupture, this study investigated the distribution and localization of both protein and mRNA for tissue (t) and urokinase (u) PA and their inhibitors type 1 (PAI-1) and type 2 (PAI-2) in amniochorion of human and rhesus monkey using conventional and confocal immunofluorescence microscopy. In situ hybridization analysis showed that the distribution and localization of mRNAs for tPA, uPA, PAI-1 and PAI-2 were similar in the fetal membranes of human and rhesus monkey; no obvious species difference was observed. Evidence of tPA mRNA was detected in amniotic epithelium, trophoblast cells and nearly all cells of the decidual layer. Strong expression of uPA mRNA was noted in the decidual cells which increased in intensity as the abscission point was approached. Weak staining in chorion laeve trophoblast was also detected. In situ hybridization experiments showed PAI-1 mRNA to be concentrated mainly in the decidual cells, some of which were interposed into the maternal-facing edge of the chorion laeve. Maximal labelling of the decidua occurred towards the zone of abscission. Weak expression of PAI-1 mRNA was also noted in some cells of the chorion laeve. The distribution of PAI-2 mRNA in amniochorion was also concentrated in the cells of the decidual layer, maximum expression of the mRNA was in the level of abscission. No detectable amount of mRNAs for tPA, uPA, PAI-1 and PAI-2 was found in the fibroblast, reticular and spongy layers. Distribution of the proteins of tPA, uPA and PAI-1 in the fetal membranes of these two species was consistent with the distribution of their mRNA. Anti-PAI-2 immunofluorescence was found to be strongly concentrated in the amniotic epithelium, but PAI-2 mRNA was negative in this layer, suggesting that the epithelium-associated PAI-2 is not of epithelial origin. These findings suggest that a local fibrinolysis in fetal membranes generated by precisely balanced expression of PAs and their inhibitors via paracrine or autocrine mechanisms may play an essential role in fetal membrane development, maturation and in membrane rupture. Following an analysis of the distribution and synthesis of activators and inhibitors it was found that they may play a role in abscission during the third stage of labour.

  • 2. Meinert, M
    et al.
    Malmström, A
    Tufvesson, E
    Westergren-Thorsson, G
    Petersen, AC
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Uldbjerg, N
    Eriksen, GV
    Labour induces increased concentrations of biglycan and hyaluronan in human fetal membranes2007In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 28, no 5-6, 482-486 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to compare hyaluronan and proteoglycans in human fetal membranes obtained before and after spontaneous labour at term.

    Study design: Prelabour samples of fetal membranes (N = 9) were obtained from elective caesarean sections and regionally sampled from over the cervix (cervical membranes) and mid-zone samples between this area and the placental edge. Postlabour samples (N = 11) were obtained from spontaneous vaginal delivery and also regionally sampled. Amnion and chorio-decidua were analysed separately. The proteoglycans decorin and biglycan were analysed using alcian blue precipitation, SDS polyacrylamide gel electrophoresis and immunostaining. Hyaluronan was analysed using a radioimmunoassay and by histochemistry. Collagen was measured by estimating hydroxyproline content.

    Results: In prelabour membranes the biglycan concentration (mu g/mg wtw) in the cervical amnion was 40% lower than in the mid-zone amnion (P < 0.05). After delivery the cervical amnion showed a twofold increase in biglycan (P < 0.05), a 30% decrease in collagen (P < 0.05), and a 50% decrease in decorin concentration (P < 0.05). In mid-zone samples after delivery the concentrations of hyaluronan showed an increase form 1.0 to 4.9 mu g/mg wtw (P < 0.05). Histology demonstrated a gelatinous substance, which separated amnion and chorio-decidua, in particular at the cervical site. This gelatinous substance contained hyaluronan at a concentration of 3.0 mu g/mg wtw.

    Conclusion: It is well established that prelabour fetal membranes are considerably stronger than postlabour fetal membranes. Two features may explain this; a weakening of the amnion combined with a separation of amnion and chorio-decidua. The biomechanical changes are consistent with the decrease in collagen and decorin, and the increase in hyaluronan and biglycan demonstrated in this study. The separation of the membranes is caused by the formation of a gelatinous substance, rich in hyaluronan. The results indicate that the biomechanical changes are not merely secondary to the stress of labour but that an active maturation process is involved.

  • 3. Metzler, Veronika M.
    et al.
    de Brot, Simone
    Robinson, Robert S.
    Jeyapalan, Jennie N.
    Rakha, Emad
    Walton, Thomas
    Gardner, David S.
    Lund, Emma F.
    Whitchurch, Jonathan
    Haigh, Daisy
    Lochray, Jack M.
    Robinson, Brian D.
    Allegrucci, Cinzia
    Fray, Rupert G.
    Persson, Jenny L.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Translational Medicine, Lund University, Malmo, Sweden.
    Odum, Niels
    Miftakhova, Regina R.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Kazan Federal University, Kazan, Republic of Tatarstan, Russian Federation.
    Rizvanov, Albert A.
    Hughes, Ieuan A.
    Tadokoro-Cuccaro, Rieko
    Heery, David M.
    Rutland, Catrin S.
    Mongan, Nigel P.
    Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development2017In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 56, 79-85 p.Article in journal (Refereed)
    Abstract [en]

    The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.

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