151. PLACENTAL HtrA3 IS REGULATED BY OXYGEN TENSION AND SERUM LEVELS ARE ALTERED DURING EARLY PREGNANCY IN WOMEN DESTINED TO DEVELOP PREECLAMPSIA

2010 ◽  
Vol 22 (9) ◽  
pp. 69
Author(s):  
G. Nie ◽  
Y. Li ◽  
M. Puryer ◽  
L. Salamonsen
Keyword(s):  
Oxygen Tension ◽  
Cellular Localization ◽  
Protein Production ◽  
Molecular Mechanisms ◽  
Serum Levels ◽  
Maternal Serum ◽  
High Oxygen ◽  
Maternal Circulation ◽  
Decidual Cells ◽  
Cloned Gene

The pathogenic origin of preeclampsia is defective placental development (placentation) and function. Preeclampsia is not diagnosed until later in pregnancy and reliable early detection is highly desirable. HtrA3 is a recently cloned gene with high expression during placentation in the mouse, rhesus monkey and human. In human 1st trimester placenta, HtrA3 is highly expressed in maternal decidual cells and in certain trophoblast cell types. Placental HtrA3 is secreted into the maternal circulation and clearly detectable in serum of pregnant women in the 1st trimester. The present study examined placental production and serum profile of HtrA3 across gestation in women, the potential molecular mechanisms regulating HtrA3 production, and association between maternal HtrA3 serum levels and preeclampsia. Immunohistochemistry determined HtrA3 expression pattern and cellular localization in 1st, 2nd and 3rd trimester placenta. Maternal serum HtrA3 levels were analysed by Western blotting. Regulation of placental HtrA3 production and secretion by oxygen tension was investigated in 1st trimester placental explants and trophoblast cells. Placental HtrA3 protein was maximally produced in the 1st trimester, then dramatically down-regulated, especially in the syncytiotrophoblast. HtrA3 was secreted into the maternal circulation with a serum profile reflecting placental production. Oxygen tension regulated HtrA3; low oxygen enhanced, while transition from low-to-high oxygen decreased, HtrA3 protein production in syncytiotrophoblast. Maternal serum HtrA3 levels at ~13-14 weeks of gestation were significantly higher in women who subsequently developed preeclampsia. It appeared that HtrA3 down-regulation was delayed in preeclamptic pregnancies. In conclusion, HtrA3 protein production is closely associated with oxygen tension in the placenta. The decline in HtrA3 at the end of 1st trimester may reflect the placental low-to-high oxygen switch. Abnormally high levels of serum HtrA3 at the end of 1st trimester is associated with preeclampsia.

Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight

1996 ◽  
Vol 148 (2) ◽  
pp. 303-309 ◽  
Author(s):  
F A Hills ◽  
J English ◽  
T Chard
Keyword(s):  
Binding Protein ◽  
Serum Levels ◽  
Maternal Serum ◽  
Significant Rise ◽  
Maternal Weight ◽  
Maternal Circulation ◽  
Gestational Weight ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract Serum levels of IGF-I and IGF-binding protein (IGFBP-1) have been determined in the maternal circulation between 11 and 42 weeks of gestation in women not in labour (n=335) and in the maternal and fetal circulations at the time of delivery between 37 and 42 weeks (n=55). Maternal serum (MS) IGF-I levels increased during pregnancy and showed a significant positive correlation with maternal weight (P=0·0033) but no correlation with birthweight. The MS IGFBP-1 levels did not change during the second and third trimesters and showed a negative correlation with birthweight, maternal weight, placental weight and MS glucose (P=0·0002, P<0·0001, P=0·047, P=0·024 respectively). MS IGFBP-1 levels were higher in small-for-gestational age babies than in average-for-gestational weight babies (P=0·026) and lower in the large-for-gestational weight group (P=0·048). There was a significant rise in mean MS IGFBP-1 levels during labour (P=0·0005). These findings suggest that IGFBP-1 may be an important factor in pathological growth retardation. Journal of Endocrinology (1996) 148, 303–309

Diagnosis and monitoring of pregnancy in mice: correlations between maternal weight, fetal and placental mass and the maternal serum levels of progesterone, pregnancy-associated murine protein-2 and α-fetoprotein

1987 ◽  
Vol 21 (4) ◽  
pp. 306-310 ◽  
Author(s):  
J. Hau ◽  
H.-J. Skovgaard Jensen
Keyword(s):  
Body Weight ◽  
Fetal Growth ◽  
Serum Levels ◽  
Maternal Serum ◽  
Separate Experiment ◽  
Maternal Weight ◽  
Maternal Circulation ◽  
Vaginal Plug ◽  
Specific Proteins ◽  
Body Weight Increase

Outbred Bom:NMRI mice were weighed daily for 18 days from observation of a vaginal plug. In a separate experiment, fetuses and placentae were weighed on each day of pregnancy. Pregnancy can be determined with 99% certainty on day 12 of gestation by the maternal body weight increase from day 1. The pregnancy-specific proteins α-fetoprotein (m-AFP) and pregnancy-associated murine protein-2 (PAMP-2), of fetal and placental origin respectively, were detectable on days 8 and 10 in the maternal circulation. Significant correlations were observed between m-AFP and fetal weight and PAMP-2 and placental weight. These markers may therefore be useful in the monitoring of fetal growth and placental growth respectively.

Interleukin-6 and Malondialdehyde in Women with Preterm Birth

2019 ◽  
Vol 15 (2) ◽  
pp. 207-212
Author(s):  
Vinita Verma ◽  
Hina Oza ◽  
Riddhi Thaker ◽  
Sunil Kumar
Keyword(s):  
Oxidative Stress ◽  
Preterm Birth ◽  
Interleukin 6 ◽  
Critical Role ◽  
Serum Levels ◽  
Maternal Serum ◽  
Full Term ◽  
Mortality And Morbidity ◽  
Term Birth ◽  
Weak Negative Correlation

Background: Preterm Birth (PTB) is one of the main causes of neonatal death and infant mortality and morbidity. The pro-inflammatory cytokine interleukin-6 (IL-6) is a major proinflammatory mediator of the host response to infection and malondialdehyde (MDA) is a marker of oxidative stress. Objective : To evaluate potential associations between IL-6 and MDA levels in women with preterm birth. Method: A total of 150 women (66 with full-term and 84 with PTB) were enrolled in this case-control study. Predesigned performas were filled through questionnaire interviews to collect data on personal, demographic, occupational, lifestyle and reproductive history. Blood samples were collected within 36 hours of delivery. Serum concentrations of IL-6 and MDA were determined in mothers with full-term and preterm birth. Results: The mean age was marginally higher; whereas BMI was slightly lower in cases (PTB) as compared to controls (full-term) subjects. Serum IL-6 and MDA levels were significantly higher in subjects with PTB than full-term birth. The data were further analyzed with respect to underweight, normal and overweight/obese BMI. In all the BMI categories, the levels of IL-6 and MDA were higher in PTB cases. Among the PTB categories, the levels of IL-6 and MDA were highest in moderate to late preterm birth. A significant positive correlation was found between IL-6 and MDA levels. There was a weak negative correlation between either IL-6 or MDA and the number of gestational weeks. Conclusion : Elevated maternal serum levels of Interleukin-6 and Malondialdehyde in preterm as compared to full-term birth might suggest that inflammation and oxidative stress play a critical role in PTB.

scholarly journals Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

2021 ◽  
Vol 22 (14) ◽  
pp. 7311
Author(s):  
Mateusz Wawro ◽  
Jakub Kochan ◽  
Weronika Sowinska ◽  
Aleksandra Solecka ◽  
Karolina Wawro ◽  
...  
Keyword(s):  
Family Member ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Psoriasis Patient ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Transcript Levels

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

scholarly journals Maternal Serum Placental Growth Factor, Soluble Fms-Like Tyrosine Kinase-1, and Soluble Endoglin in Twin Gestations and the Risk of Preeclampsia—A Systematic Review

2020 ◽  
Vol 9 (1) ◽  
pp. 183 ◽  
Author(s):  
Katarzyna Kosinska-Kaczynska ◽  
Magdalena Zgliczynska ◽  
Szymon Kozlowski ◽  
Lukasz Wicherek
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Serum Levels ◽  
Maternal Serum ◽  
Placental Growth Factor ◽  
Cochrane Library ◽  
Original Research ◽  
Multiple Gestation ◽  
Soluble Endoglin ◽  
Twin Pregnancies

Multiple gestation is one of the key risk factors for the occurrence of preeclampsia (PE). Soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin are molecules involved in the process of angiogenesis with a proven role in the pathogenesis of PE. The aim of the review was to summarize available data on maternal serum levels of the above-mentioned factors and their usefulness in predicting PE in twin pregnancies. Only original research articles written in English were considered eligible. Reviews, chapters, case studies, conference papers, experts’ opinions, editorials, and letters were excluded from the analysis. No publication date limitations were imposed. The systematic literature search using PubMed/MEDLINE, Scopus, Embase, and Cochrane Library databases identified 338 articles, 10 of which were included in the final qualitative analyses. The included studies showed significant differences in maternal serum levels of the discussed factors between women with twin pregnancies with PE and those who did not develop PE, and their promising performance in predicting PE, alone or in combination with other factors. The identification of the most effective algorithms, their prompt introduction to the clinical practice, and further assessment of the real-life performance should become a priority.

scholarly journals The passage of antibodies from the maternal circulation into the embryo in rabbits

1948 ◽  
Vol 135 (880) ◽  
pp. 390-403 ◽  
Keyword(s):  
High Titre ◽  
Immune Serum ◽  
Maternal Serum ◽  
Yolk Sac ◽  
Passive Immunity ◽  
Maternal Circulation ◽  
Active Immunity ◽  
Foreign Proteins ◽  
Positive Results ◽  
Rabbit Embryos

Active immunity to Brucella abortus was induced in adult female rabbits. They were mated a week after the last injection of antigen and were killed and the yolk-sac contents of the embryos tested for agglutinins 8½ days after copulation. Specific agglutinins were found to be present in the yolk-sac contents in all cases. The titre varied significantly from embryo to embryo in the same litter, and was in some as high as that in the maternal serum at the time of killing. Passive immunity to Br. abortus was imparted to female rabbits 7 to 9 days pregnant by intravenous injection of immune serum of high titre. The rabbits were killed and the yolk-sac fluid of the embryos tested for agglutinins 10 to 17 hr. after injection. Specific agglutinins were present in most of the embryos from five of the six rabbits injected before 8 days post-coitum. All the embryos in the sixth rabbit were regressing. Specific agglutinins were not found in any of the embryos from two rabbits injected after 9 days post-coitum, by which time the yolk-sac fluid has ceased to increase in volume. Positive results were obtained both when rabbit and bovine immune sera were used. Active immunity to Br. abortus was induced in pregnant rabbits by injections beginning after the 15th day post-coitum. The serum of the newborn young, removed from their immune mothers before they had suckled, was tested and specific agglutinins were found to be present with a titre corresponding to that of the maternal serum. It was concluded that agglutinins, whether actively or passively acquired, pass freely from the maternal circulation into the yolk-sacs of 7- and 8-day rabbit embryos. This constitutes a delicate test of the passage of protein without alteration through the yolk-sac wall. The yolk-sac wall does not appear to be selective, since it is at least as permeable to foreign proteins as it is to those of maternal origin. Agglutinins pass from the maternal circulation into the embryo after the disappearance of the bilaminar wall of the yolk-sac also, either by way of the yolk-sac splanchnopleur or the allantochorionic placenta or both. The bearing of these results on current theories of placental permeability are discussed.

Sign in / Sign up

Export Citation Format

Share Document