| 1. |
- Amer-Wåhlin, Isis, et al.
(författare)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
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Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 2. |
- Bottalico, Barbara
(författare)
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Monoamine transporters in female human reproduction.
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study explored the gene and protein expression of the monoamine transporters in human endometrium throughout the menstrual cycle, in early decidua and in placentas from normal as well as preeclamptic pregnancies using in-situ hybridization, real time-PCR, immunohistochemistry and primary tissue cultures. Four distinguishable patterns were observed in the endometrium over the menstrual cycle: (1) epithelial expression of norepinephrine transporter (NET) mRNA, (2) Stromal co- expression of vesicular monoamine transporter 2 (VMAT2) and plasma membrane monoamine transporter (PMAT) mRNAs with maximal intensity in the proliferative phase; (3) increasing epithelial expression of VMAT2 mRNA with a maximum in the late secretory phase; (4) stromal expression of extra-neuronal monoamine transporter (EMT) mRNA with a peak in the early secretory phase. The presence of functional EMT and VMAT2 transporter proteins throughout the menstrual cycle was shown by uptake of radiolabelled histamine. A similar expression pattern of monoamine transporters was seen in normal and preeclamptic placentas. In particular, NET mRNA was detected in the chorionic and anchoring villi while EMT mRNA was expressed in scattered cells in placental vessels as well as in intralobular septa cells. Serotonin transporter (SERT) mRNA was mainly detected in the chorionic villi. VMAT2 mRNA was detected in the deeper layers of the placenta bed biopsies in trophoblast cells. A small number of cells in the intima layer of some placental vessels showed mRNA expression of the organic cation transporters 1 and 2 (OCT1 and OCT2). Although the expression pattern was similar, a significantly lower gene expression of NET and EMT was found in placentas obtained from preeclamptic versus normal pregnancies. Our results suggest that monoamine transports may have specific functions in female human reproduction by maintaining adequate levels of extra cellular monoamines. Their presence and dynamic expression suggests an important role during the menstrual cycle and pregnancy. Moreover a defective gene expression or function of the monoamine transporters might be determinant in the onset of preeclampsia and its alteration in the vascular bed. Knowledge of the regulation of monoamine metabolism in the endometrium, decidua and placenta will increase the understanding of infertility problems and may offer new pharmacological approaches to optimise assisted reproduction and treatment of preeclampsia.
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| 3. |
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| 4. |
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| 5. |
- Brownbill, Paul, et al.
(författare)
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An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy
- 2016
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238. ; 64, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.
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| 6. |
- Casslén, Vera, et al.
(författare)
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Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2
- 2006
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 12:8, s. 483-489
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Tidskriftsartikel (refereegranskat)abstract
- Cellular reuptake of monoamines, which is mediated by cell membrane transporters, is followed by accumulation in vesicles by vesicular monoamine transporters (VMAT). The aim of this study was to demonstrate the presence of functional monoamine transporters with high affinity for histamine in human endometrial tissue, since histamine has been implicated as a paracrine signal during endometrial decidualization and embryo implantation. In situ hybridization with S-35-labelled cRNA probes was used for detection of the organic cationic transporter-2 (OCT-2), the extraneuronal monoamine transporter (EMT), and VMAT-2 in cryosections of normal human endometrial tissue. To identify functional transporters for histamine in endometrial cells, we incubated primary cultures of stromal cells and cultures of attached glands with H-3-labelled histamine. Cultures were pretreated with either corticosterone, a specific inhibitor of EMT, or reserpine, a specific inhibitor of VMAT-2. EMT mRNA was localized in the stroma with peak expression in the secretory phase, whereas OCT-2 mRNA was expressed by few cells in the stroma throughout the cycle. VMAT-2 mRNA was localized in the stroma during the proliferative phase and in the epithelium during the secretory phase. Thus, EMT and VMAT-2, which both have high affinity for histamine, are strongly expressed in endometrial cells. Both corticosterone and reserpine significantly reduced the uptake of H-3-histamine in stromal cells during the proliferative as well as the secretory phase. This indicates the presence of functional EMT and VMAT-2 transporter proteins throughout the cycle, even though their periods of maximal mRNA expression were limited. The results of uptake experiments with glandular epithelial cells confirmed not only the presence of functional VMAT-2 transporter protein in the secretory phase but also the absence of a histamine-specific plasma membrane transporter throughout the cycle. Thus, endometrial tissue contains both plasma membrane and vesicular membrane monoamine transporters with high affinity for histamine. They can potentially influence the reproductive process by the uptake of extracellular histamine and subsequent release on demand.
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| 7. |
- Hansson, Stefan R, et al.
(författare)
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Monoamine transporters in human endometrium and decidua.
- 2009
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 2008:Nov 5, s. 249-260
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Monoamines play important roles in decidualization, implantation, immune modulation and inflammation. Furthermore, monoamines are potent vasoactive mediators that regulate blood flow and capillary permeability. Regulation of the uterine blood flow is important both during menstruation and pregnancy. Adequate monoamine concentrations are essential for a proper implantation and physiological development of pregnancy. Unlike most transmitter substances, monoamines are recycled by monoamine transporters rather than enzymatically inactivated. Their intracellular fate is influenced by their lower affinity for inactivating enzymes than for vesicular transporters located in intracellular vesicles. Thus, cells are capable not only of recapturizing and degrading monoamines, but also of storing and releasing them in a controlled fashion. METHODS The general objective of the present review is to summarize the role of the monoamine transporters in the female human reproduction. Since the transporter proteins critically regulate extracellular monoamine concentrations, knowledge of their distribution and cyclic variation is of great importance for a deeper understanding of the contribution of monoaminergic mechanisms in the reproductive process. MEDLINE was searched for relevant publications from 1950 to 2007. RESULTS Two families of monoamine transporters, neuronal and extraneuronal monoamine transporters, are present in the human endometrium and deciduas. CONCLUSIONS New knowledge about monoamine metabolism in the endometrium during menstruation and pregnancy will increase understanding of infertility problems and may offer new pharmacological approaches to optimize assisted reproduction.
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