Environmental effects on stem water deficit in co-occurring conifers exposed to soil dryness.

PubMed

Oberhuber, Walter; Kofler, Werner; Schuster, Roman; Wieser, Gerhard

2015-04-01

We monitored dynamics of stem water deficit (ΔW) and needle water potential (Ψ) during two consecutive growing seasons (2011 and 2012) in a dry inner Alpine environment (750 m above sea level, Tyrol, Austria), where Pinus sylvestris, Picea abies and Larix decidua form mixed stands. ΔW was extracted from stem circumference variations, which were continuously recorded by electronic band dendrometers (six trees per species) and correlations with environmental variables were performed. Results revealed that (i) ΔW reached highest and lowest values in P. abies and L. decidua, respectively, while mean minimum water potential (Ψ(ea)) amounted to -3.0 MPa in L. decidua and -1.8 MPa in P. abies and P. sylvestris. (ii) ΔW and Ψ(ea) were significantly correlated in P. abies (r = 0.630; P = 0.038) and L. decidua (r = 0.646; P = 0.032). (iii) In all species, ΔW reached highest values in late summer and was most closely related to temperature (P < 0.001). Results indicate that all species were undergoing water limitations as measured by increasing ΔW throughout the growing season, whereby P. abies most strongly drew upon water reserves in the living tissues of the bark. Quite similar ΔW developed in drought-sensitive L. decidua and drought-tolerant P. sylvestris indicate that various water storage locations are depleted in species showing different strategies of water status regulation, i.e. anisohydric vs. isohydric behavior, respectively, and/or water uptake efficiency differs among these species. Close coupling of ΔW to temperature suggests that climate warming affects plant water status through its effect on atmospheric demand for moisture.

Environmental effects on stem water deficit in co-occurring conifers exposed to soil dryness

NASA Astrophysics Data System (ADS)

Oberhuber, Walter; Kofler, Werner; Schuster, Roman; Wieser, Gerhard

2015-04-01

We monitored dynamics of stem water deficit (Δ W) and needle water potential ( Ψ) during two consecutive growing seasons (2011 and 2012) in a dry inner Alpine environment (750 m above sea level, Tyrol, Austria), where Pinus sylvestris, Picea abies and Larix decidua form mixed stands. Δ W was extracted from stem circumference variations, which were continuously recorded by electronic band dendrometers (six trees per species) and correlations with environmental variables were performed. Results revealed that (i) Δ W reached highest and lowest values in P. abies and L. decidua, respectively, while mean minimum water potential ( Ψ ea) amounted to -3.0 MPa in L. decidua and -1.8 MPa in P. abies and P. sylvestris. (ii) Δ W and Ψ ea were significantly correlated in P. abies ( r = 0.630; P = 0.038) and L. decidua ( r = 0.646; P = 0.032). (iii) In all species, Δ W reached highest values in late summer and was most closely related to temperature ( P < 0.001). Results indicate that all species were undergoing water limitations as measured by increasing Δ W throughout the growing season, whereby P. abies most strongly drew upon water reserves in the living tissues of the bark. Quite similar Δ W developed in drought-sensitive L. decidua and drought-tolerant P. sylvestris indicate that various water storage locations are depleted in species showing different strategies of water status regulation, i.e. anisohydric vs. isohydric behavior, respectively, and/or water uptake efficiency differs among these species. Close coupling of Δ W to temperature suggests that climate warming affects plant water status through its effect on atmospheric demand for moisture.

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy*

PubMed Central

Zuo, Ru-Juan; Gu, Xiao-Wei; Qi, Qian-Rong; Wang, Tong-Song; Zhao, Xu-Yu; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Decidualization is an essential process of maternal endometrial stromal cells to support pregnancy. Although it is known that enhanced glucose influx is critical for decidualization, the underlying mechanism in regulating glucose metabolism in decidua remains insufficiently understood. Here, we demonstrate that aerobic glycolysis-related genes and factors are all substantially induced during decidualization, indicating the existence of Warburg-like glycolysis in decidua. In vitro, progesterone activates hypoxia-inducible factor 1α (Hif1α) and c-Myc through Pi3k-Akt signaling pathway to maintain aerobic glycolysis in decidualizing cells. Knocking down of pyruvate kinase M2 (Pkm2) attenuates the induction of decidual marker gene. Decidual formation in vivo is also impaired by glycolysis inhibitor 3-bromopyruvate. Besides, lactate exporter monocarboxylate transporter 4 (Mct4) is induced in newly formed decidual cells, whereas lactate importer Mct1 and proliferation marker Ki-67 are complementarily located in the surrounding undifferentiated cells, which are supposed to consume lactate for proliferation. Hif1α activation is required for lactate-dependent proliferation of the undifferentiated cells. Inhibition of lactate flux leads to compromised decidualization and decelerated lactate-dependent proliferation. In summary, we reveal that Warburg-like glycolysis and local lactate shuttle are activated in decidua and play important roles for supporting early pregnancy. PMID:26178372

[Trophoblast: conductor of the maternal immune tolerance].

PubMed

Mesdag, V; Salzet, M; Vinatier, D

2014-11-01

Pregnancy is a temporary semi-allograft that survives for nine months. The importance of this event for the survival of the species justifies several tolerance mechanisms that are put into place at the beginning of pregnancy, some of which occur even at the time of implantation. The description of these mechanisms underlines the leadership of the trophoblast. The trophoblast is the conductor of the events, protects himself by expressing specific antigens and regulates the environment of the decidua according to the calendar of the events of the pregnancy The trophoblast and the decidual environment attract the effectors of immunity, almost all present in the decidua. The immunological atmosphere of the decidua evolves during the pregnancy modulating the level of activation of the immunological cells and adapting the level of activation to the stage of the pregnancy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Placenta accreta: diagnosis, management and the molecular biology of the morbidly adherent placenta.

PubMed

Goh, William A; Zalud, Ivica

2016-01-01

Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and insulin-like 4, an insulin-like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta.

Placenta accreta: Diagnosis, management and the molecular biology of the morbidly adherent placenta

PubMed Central

Goh, William; Zalud, Ivica

2017-01-01

Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and INSL4, an insulin like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta. PMID:26135782

The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory response during early pregnancy

PubMed Central

Heyward, CY; Sones, JL; Lob, HE; Yuen, LC; Abbott, KE; Huang, W; Begun, ZR; Butler, SD; August, A; Leifer, CA; Davisson, RL

2017-01-01

Preeclampsia is a devastating complication of pregnancy characterized by late-gestation hypertension and proteinuria. Because the only definitive treatment is delivery of the fetus and placenta, preeclampsia contributes to increased morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which spontaneously develops a syndrome strikingly similar to preeclampsia, displays excessive inflammation and suppression of inflammation improves pregnancy outcomes. During early pregnancy, decidual macrophages play an important role in promoting maternal tolerance to fetal antigens and regulating tissue remodeling, two functions that are critical for normal placental development. BPH/5 pregnancies are characterized by abnormal placentation; therefore, we hypothesized that macrophage localization and/or function is altered during early pregnancy at the site of placental formation (the decidua) compared to C57BL/6 controls. At early gestation time points, before the onset of maternal hypertension or proteinuria, there was a reduction in the number of macrophages in BPH/5 decidua and a concomitant increase in activated T cells compared to C57BL/6. BPH/5 decidua also exhibited decreased expression of the immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory, inducible nitric oxide synthase (iNOS). Together, these data suggest that a reduction in decidual macrophages during pregnancy is associated with immune activation in BPH/5 mice, inadequate placental development and may contribute to adverse pregnancy outcomes in this model. PMID:28432903

Effects of maternal dietary olive oil on pathways involved in diabetic embryopathy.

PubMed

Higa, Romina; Roberti, Sabrina Lorena; Musikant, Daniel; Mazzucco, María Belén; White, Verónica; Jawerbaum, Alicia

2014-11-01

Maternal diabetes induces a pro-oxidant/pro-inflammatory intrauterine environment related to the induction of congenital anomalies. Peroxisome proliferator activated receptors (PPARs) are transcription factors that regulate antioxidant and anti-inflammatory pathways. We investigated whether maternal diets supplemented with olive oil, enriched in oleic acid, a PPAR agonist, can regulate the expression of PPAR system genes, levels of lipoperoxidation and activity of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in embryos and decidua from diabetic rats. The embryos and decidua from diabetic rats showed reduced expression of PPARs and increased concentration of lipoperoxidation, MMPs and TIMPs, whereas the maternal treatments enriched in olive oil increased PPARδ in embryos and PPARγ and PPARγ-coactivator-1α expression in decidua, and increased TIMPs concentrations and decreased lipoperoxidation and MMPs activity in both tissues. Thus, maternal diets enriched in olive oil can regulate embryonic and decidual PPAR system genes expression and reduce the pro-oxidant/pro-inflammatory environment during rat early organogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

A transcriptional profile of the decidua in preeclampsia

PubMed Central

LØSET, Mari; MUNDAL, Siv B.; JOHNSON, Matthew P.; FENSTAD, Mona H.; FREED, Katherine A.; LIAN, Ingrid A.; EIDE, Irina P.; BJØRGE, Line; BLANGERO, John; MOSES, Eric K.; AUSTGULEN, Rigmor

2010-01-01

OBJECTIVE To obtain insight into possible mechanisms underlying preeclampsia using genome-wide transcriptional profiling in decidua basalis. STUDY DESIGN Genome-wide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal pregnancies (n = 58). Differentially expressed genes were identified and merged into canonical pathways and networks. RESULTS Of the 26,504 expressed transcripts detected, 455 were differentially expressed (P <0.05, FDR P <0.1). Both novel (ARL5B, SLITRK4) and previously reported preeclampsia-associated genes (PLA2G7, HMOX1) were identified. Pathway analysis revealed that ‘tryptophan metabolism’, ‘endoplasmic reticulum stress’, ‘linoleic acid metabolism’, ‘notch signaling’, ‘fatty acid metabolism’, ‘arachidonic acid metabolism’ and ‘NRF2-mediated oxidative stress response’ were overrepresented canonical pathways. CONCLUSION In the present study single genes, canonical pathways and gene-gene networks that are likely to play an important role in the pathogenesis of preeclampsia, have been identified. Future functional studies are needed to accomplish a greater understanding of the mechanisms involved. PMID:20934677

Measurement of cell death by oxidative stress in three-dimensional spheroids from trophoblast and in fragments of decidua tissue.

PubMed

Theuerkauf, Regine-Susanne; Ahammer, Helmut; Siwetz, Monika; Helige, Christine; Dohr, Gottfried; Walcher, Wolfgang; Palacio, José Ramón; Martinez, Paz; Sedlmayr, Peter

2010-05-01

We report a new morphometric method for measurement of the amount of cell death in three-dimensional multicellular spheroids of the trophoblast-like cell line AC1-M59 and of cultured pieces of decidua tissue (decidua spheroids) in response to a cytotoxic agent. The viability of the spheroids was assessed by adding propidium iodide to the culture medium at the end of the toxic treatment. On fluorescence and brightfield images of serial cryosections the areas of propidium iodide fluorescence and the entire corresponding spheroids were measured by applying digital image processing and ratiometrical quantification. As an example, we evaluated the cytotoxic effect of hydrogen peroxide on both types of spheroids. The relative potency of hydrogen peroxide to induce tissue damage was assessed quantitatively for determination of the minimal concentration that leads to an increase in cytotoxicity. The method presented suggests general applicability for in vitro determination of toxicity against tissues. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy

PubMed Central

Wang, S-C; Li, Y-H; Piao, H-L; Hong, X-W; Zhang, D; Xu, Y-Y; Tao, Y; Wang, Y; Yuan, M-M; Li, D-J; Du, M-R

2015-01-01

CD8+ T cells are critical in the balance between fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T cells from decidua greatly outnumbered those from peripheral blood during human early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+ and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co-expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in decidua. This population exhibited high proliferative activity and Th2-type cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in vitro proliferation and Th2-type cytokine production while increased trophoblast killing and IFN-γ producing capacities of CD8+ T cells. Pregnant CBA/J females challenged with Tim-3 and/or PD-1 blocking antibodies were more susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction. Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were significantly impaired in miscarriage. These findings underline the important roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and maintaining normal pregnancy. PMID:25950468

[The conservative treatment of placenta accreta. A clinical case report].

PubMed

Artuso, A; Rocchi, B; Garbo, S; Baudino, G; Repetti, F

1993-09-01

The following description is a clinical case of placenta accreta and its conservative treatment. According to some authors, abnormal adhesion of the placenta depends on the alteration of the equilibrium between the trophoblastic tissue invasion and the reaction of the decidua. Consequently we have various degrees of penetration of the myometrium by chorionic villi into areas of deficit, sparse or absent decidua. Whatever the pathogenetic mechanism, the final clinical picture is slight to deep penetration of the trophoblastic tissue into the uterine wall. That causes absence of the normal plane of cleavage between placenta and maternal decidua, no spontaneous placental detachment during the third stage of labour and no possible manual removal. The patient, primigravida, was admitted at the 36th Week of gestation with PROM and physiologically delivered a neonate weighing 1820 g, after she spontaneously began labour. The newborn was admitted in the neonatal-pathology ward because it was premature although the Apgar score at 1-5 minutes after birth was 5-9. Placental ejection was awaited for 1 hour, then manual exploration of the uterine cavity was undertaken. The normal plane of cleavage between placental tissue and decidua was absent and therefore manual extraction of the placenta was impossible. Surgery was stopped and, after informed consensus was obtained from the patient, a conservative treatment was tried. After cutting the umbilical cord as short as possible and checking for vaginal bleeding, the patient was moved to obstetrics ward.(ABSTRACT TRUNCATED AT 250 WORDS)

History of Larix decidua Mill. (European larch) since 130 ka

NASA Astrophysics Data System (ADS)

Wagner, Stefanie; Litt, Thomas; Sánchez-Goñi, Maria-Fernanda; Petit, Rémy J.

2015-09-01

Retrospective studies focussing on forest dynamics using fossil and genetic data can provide important keys to prepare forests for the future. In this study we analyse the impact of past climate and anthropogenic changes on Larix decidua Mill. (European larch) populations based on a new range-wide fossil compilation encompassing the last 130 ka and on recently produced genetic data (nuclear, mitochondrial). Results demonstrate that during the last 130 ka L. decidua persisted close to its current distribution range and colonized vast areas outside this range during the first two early Weichselian interstadials (c. 87-109 ka and c. 83-78 ka), reaching a distributional maxima in the north-central European lowlands. Some fossil sites point to notably rapid responses to some abrupt climate events (Dansgaard-Oeschger cycles and Heinrich Events). Combined fossil and genetic data identify at least six MIS 2 refuges and postglacial recolonization pathways. The establishment of extant L. decidua forests dates back to the first two millennia of the Holocene (c. 11.5-9.5 ka) and the onset of anthropogenic impact was inferred since the late Neolithic (c. 6 ka), with major changes occurring since the Bronze Age (c. 4 ka). During the last 300 years human-induced translocations resulted in recent admixture of populations originating from separate refuges. Altogether, the results of this study provide valuable clues for developing sustainable conservation and management strategies targeting ancient genetic lineages and for studying evolutionary issues.

The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory response during early pregnancy.

PubMed

Heyward, C Y; Sones, J L; Lob, H E; Yuen, L C; Abbott, K E; Huang, W; Begun, Z R; Butler, S D; August, A; Leifer, C A; Davisson, R L

2017-04-01

Preeclampsia is a devastating complication of pregnancy characterized by late-gestation hypertension and proteinuria. Because the only definitive treatment is delivery of the fetus and placenta, preeclampsia contributes to increased morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which spontaneously develops a syndrome strikingly similar to preeclampsia, displays excessive inflammation and suppression of inflammation improves pregnancy outcomes. During early pregnancy, decidual macrophages play an important role in promoting maternal tolerance to fetal antigens and regulating tissue remodeling, two functions that are critical for normal placental development. BPH/5 pregnancies are characterized by abnormal placentation; therefore, we hypothesized that macrophage localization and/or function is altered during early pregnancy at the site of placental formation (the decidua) compared to C57BL/6 controls. At early gestation time points, before the onset of maternal hypertension or proteinuria, there was a reduction in the number of macrophages in BPH/5 decidua and a concomitant increase in activated T cells compared with C57BL/6. BPH/5 decidua also exhibited decreased expression of the immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory, inducible nitric oxide synthase. Together, these data suggest that a reduction in decidual macrophages during pregnancy is associated with immune activation in BPH/5 mice, inadequate placental development and may contribute to adverse pregnancy outcomes in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage.

PubMed

Higa, R; Kurtz, M; Mazzucco, M B; Musikant, D; White, V; Jawerbaum, A

2012-05-01

Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.

IFPA Meeting 2010 Workshops Report II: Placental pathology; Trophoblast invasion; Fetal sex; Parasites and the placenta; Decidua and embryonic or fetal loss; Trophoblast differentiation and syncytialisation

PubMed Central

Al-Khan, A; Aye, IL; Barsoum, I; Borbely, A; Cebral, E; Cerchi, G; Clifton, VL; Collins, S; Cotechini, T; Davey, A; Flores-Martin, J; Fournier, T; Franchi, AM; Fretes, RE; Graham, CH; Godbole, G; Hansson, SR; Headley, PL; Ibarra, C; Jawerbaum, A; Kemmerling, U; Kudo, Y; Lala, PK; Lassance, L; Lewis, RM; Menkhorst, E; Morris, C; Nobuzane, T; Ramos, G; Rote, N; Saffery, R; Salafia, C; Sarr, D; Schneider, H; Sibley, C; Singh, AT; Sivasubramaniyam, TS; Soares, MJ; Vaughan, O; Zamudio, S; Lash, GE

2016-01-01

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb. 4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. PMID:21236487

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

PubMed Central

Makrigiannakis, Antonis; Vrekoussis, Thomas; Zoumakis, Emmanouel; Kalantaridou, Sophia N.; Jeschke, Udo

2017-01-01

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. PMID:28629172

Decidual activin: its role in the apoptotic process and its regulation by prolactin.

PubMed

Tessier, Christian; Prigent-Tessier, Anne; Bao, Lei; Telleria, Carlos M; Ferguson-Gottschall, Susan; Gibori, Gil B; Gu, Yan; Bowen-Shauver, Jennifer M; Horseman, Nelson D; Gibori, Geula

2003-05-01

Successful pregnancy requires profound differentiation and reorganization of the uterine tissues including, as pregnancy progresses, extensive apoptosis of decidual tissue to accommodate the developing conceptus. We have previously shown a positive correlation between expression of activin A and apoptosis in the decidua and have also shown that expression of activin A occurs at the time when prolactin (PRL) receptors disappear from decidual cells. The goals of this study were to examine whether activin A plays a role in decidual apoptosis and whether expression of activin A in the decidua is regulated by PRL and placental lactogens. Studies were carried out using primary rat decidual cells, a decidual cell line (GG-AD), and PRL null mice. Treatment of decidual cells with activin A significantly increased DNA degradation, caspase 3 activity, and caspase 3 mRNA expression. However, this effect was observed only in the absence of endogenous activin production by these cells. Addition of follistatin to decidual cells that were producing activin A decreased both caspase 3 activity and mRNA expression. Similarly, addition of activin-blocking antibodies to cultures of GG-AD cells, which also produce activin A, caused a reduction in both DNA degradation and caspase 3 activity. PRL and placental lactogens caused an inhibition of activin A mRNA expression in primary decidual cells. Even more convincingly, decidua of PRL null mice expressed abundant activin A at a time when no expression of this hormone is detected in wild-type mice and treatment of PRL null mice with PRL caused a profound inhibition of activin A mRNA expression. In summary, our investigations into the role and regulation of decidual activin have revealed that activin A can induce cell death in the decidua and that its expression is under tight regulation by PRL and placental lactogens.

Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy.

PubMed

Huang, Yu; Zhu, Xiao-Yong; Du, Mei-Rong; Li, Da-Jin

2008-02-15

During human early pregnancy, fetus-derived trophoblasts come into direct contact with maternal immune cells at the maternofetal interface. At sites of placental attachment, invasive extravillous trophoblasts encounter decidual leukocytes (DLC) that accumulate within the decidua. Because we first found chemokine CXCL16 was highly expressed in and secreted by the first-trimester human trophoblasts previously, in this study we tested the hypothesis of whether the fetal trophoblasts can direct migration of maternal T lymphocyte and monocytes into decidua by secreting CXCL16. We analyzed the transcription and translation of CXCL16 in the isolated first-trimester human trophoblast, and examined the kinetic secretion of CXCL16 in the supernatant of the primary-cultured trophoblasts. We demonstrated that the sole receptor of CXCL16, CXCR6, is preferentially expressed in T lymphocytes, NKT cells, and monocytes, hardly expressed in two subsets of NK cells from either the peripheral blood or decidua. We further demonstrated the chemotactic activity of CXCL16 in the supernatant of the primary trophoblast on the peripheral mononuclear cells and DLC. Moreover, the CXCL16/CXCR6 interaction is involved in the migration of the peripheral T lymphocytes, gammadelta T cells, and monocytes, but not NKT cells. In addition, the trophoblast-conditioned medium could enrich PBMC subsets selectively to constitute a leukocyte population with similar composition to that of DLC, which suggests that the fetus-derived trophoblasts can attract T cells, gammadelta T cells, and monocytes by producing CXCL16 and interaction with CXCR6 on these cells, leading to forming a specialized immune milieu at the maternofetal interface.

Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo-maternal interface.

PubMed

Baston-Buest, Dunja M; Porn, Anne C; Schanz, Andrea; Kruessel, Jan-S; Janni, Wolfgang; Hess, Alexandra P

2011-02-01

Angiogenesis is required for successful implantation of the invading blastocyst. Vascular endothelial growth factor (VEGF) is an important key player in angiogenesis and vascular remodeling during the implantation process. Besides its well-characterized receptors VEGFR1 and VEGFR2, neuropilin-1 (NRP-1) has been shown to play an additional role in the signaling process of angiogenesis in human endometrium during the menstrual cycle, as a co-receptor of VEGF. These findings led to the hypothesis that NRP-1 might play a role in the vascular remodeling process during embryo implantation and the establishment of a pregnancy. NRP-1 mRNA transcript and protein expression were investigated in human choriocarcinoma cell lines (JEG-3, Jar and BeWo) aiming to evaluate the expression of NRP-1 in vitro, as well as in human decidua of all three trimesters of pregnancy, by western blot analysis (three samples of each trimester of pregnancy). The localization of NRP-1 in human decidua of all three trimesters of pregnancy was analyzed by immunohistochemistry (five samples of each trimester of pregnancy). NRP-1 transcript and protein were expressed in all cell lines examined. Corresponding to the analysis of human tissue by western blot and the localization by immunohistochemistry, NRP-1 protein higher expressed in samples of early pregnancy in comparison to the end of pregnancy. NRP-1 was expressed in the decidua, villi and invading cytotrophoblast of all samples investigated. This is the first study clearly showing the expression of NRP-1 in human decidua and trophoblast, suggesting an important role for the VEGF co-receptor NRP-1 besides the established receptor VEGFR2 at the embryo-maternal interface during embryonic implantation and placentation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.

PubMed

Higa, R; White, V; Martínez, N; Kurtz, M; Capobianco, E; Jawerbaum, A

2010-04-01

Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved in diabetic embryopathy. Previous works have found diminished concentrations of PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of increasing embryonic PGE(2) concentrations through the activation of the nuclear receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils, respectively. The aim of this study was to analyze the capability of dietary supplementation with either 6% olive or 6% safflower oils to regulate PGE(2), PGI(2) and NO concentrations in embryos and deciduas from control and diabetic rats during early organogenesis. Diabetes was induced by a single injection of streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil-supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were measured by EIA and NO through the evaluation of its stable metabolites nitrates-nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower oil-supplemented treatments highly reduced resorption and malformation rates in diabetic animals, and that they were able to prevent maternal diabetes-induced alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover, these dietary treatments prevented NO overproduction in embryos and deciduas from diabetic rats. These data indicate that in maternal diabetes both the embryo and the decidua benefit from the olive and safflower oil supplementation probably through mechanisms that involve the rescue of aberrant prostaglandin and NO generation and that prevent developmental damage during early organogenesis.

Mesenchymal stem cells reside in a vascular niche in the decidua basalis and are absent in remodelled spiral arterioles.

PubMed

Kusuma, G D; Manuelpillai, U; Abumaree, M H; Pertile, M D; Brennecke, S P; Kalionis, B

2015-03-01

Maternal decidua basalis tissue attached to the placenta following delivery is a source of decidual mesenchymal stem cells (DMSCs). The in vitro characteristics of DMSCs have been partly defined but their in vivo function(s) are poorly understood. The anatomic location, or niche, provides clues regarding potential in vivo function(s) of DMSCs, but the niche has not been described. Cells were isolated from the decidua basalis and flow cytometric analyses showed the expected phenotypic profile for MSC cell surface markers. In vitro, the cells differentiated into adipocytes, osteocytes, and chondrocytes. DMSCs were then stained with antibodies by immunofluorescence detection. Immunocytochemistry revealed that DMSCs were positive for FZD-9, STRO-1, 3G5, and α-SMA as expected and lacked expression of vWF and Ck7. Fluorescence in situ hybridization analysis showed the cultured cells were of maternal origin. Immunofluorescence was carried out on placental bed biopsies using the FZD-9, STRO-1, 3G5, and α-SMA antibodies. DMSCs were located in the vascular niche in decidua basalis. Immunofluorescence with antibodies to FZD-9, Ck7 and vWF revealed DMSCs in the vascular niche surrounding intact non-transformed spiral arterioles but DMSCs were absent in fully transformed spiral arterioles. Spiral arteriole remodelling is a critical feature of human pregnancy. The DMSC niche was investigated in fully transformed and non-transformed spiral arterioles. DMSCs have not been previously implicated in spiral arteriole remodelling. The absence of DMSCs around fully transformed spiral arterioles suggests they are a target for replacement or destruction by invading placental extravillous trophoblast cells, which carry out spiral arteriole remodelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serum from pregnant women with gestational diabetes mellitus increases the expression of FABP4 mRNA in primary subcutaneous human pre-adipocytes

PubMed Central

Li, Lan; Lee, Se Jin; Kook, Song Yi; Ahn, Tae Gyu; Lee, Ji Yeon

2017-01-01

Objective Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group. Methods We obtained placentas, deciduas, and serum from 12 pregnant women with GDM and 12 normal pregnant women and performed enzyme-linked immunosorbent assay, real time quantitative-polymerase chain reaction. We cultured human pre-adipocytes for 17 days with GDM and non-GDM serum and performed western blot, real time quantitative-polymerase chain reaction, and oil red O staining. Results Expression of FABP4 in serum, placenta and decidua of pregnant women with GDM was significantly higher than that in normal pregnant women. Serum from pregnant women with GDM increased the expression of FABP4 mRNA and decreased the expression of adiponectin mRNA in human pre-adipocytes significantly. Adipocyte cultured in GDM serum showed significantly greater lipid accumulation than those cultured in normal serum. Conclusion Our results suggest that FABP4 is higher in placenta and decidua from pregnant women with GDM. Increased circulating FABP4 in maternal serum from pregnant women with GDM may originate from adipocytes and the placenta. Circulating FABP4 can induce increased insulin resistance and decreased insulin sensitivity. PMID:28534013

Serum from pregnant women with gestational diabetes mellitus increases the expression of FABP4 mRNA in primary subcutaneous human pre-adipocytes.

PubMed

Li, Lan; Lee, Se Jin; Kook, Song Yi; Ahn, Tae Gyu; Lee, Ji Yeon; Hwang, Jong Yun

2017-05-01

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group. We obtained placentas, deciduas, and serum from 12 pregnant women with GDM and 12 normal pregnant women and performed enzyme-linked immunosorbent assay, real time quantitative-polymerase chain reaction. We cultured human pre-adipocytes for 17 days with GDM and non-GDM serum and performed western blot, real time quantitative-polymerase chain reaction, and oil red O staining. Expression of FABP4 in serum, placenta and decidua of pregnant women with GDM was significantly higher than that in normal pregnant women. Serum from pregnant women with GDM increased the expression of FABP4 mRNA and decreased the expression of adiponectin mRNA in human pre-adipocytes significantly. Adipocyte cultured in GDM serum showed significantly greater lipid accumulation than those cultured in normal serum. Our results suggest that FABP4 is higher in placenta and decidua from pregnant women with GDM. Increased circulating FABP4 in maternal serum from pregnant women with GDM may originate from adipocytes and the placenta. Circulating FABP4 can induce increased insulin resistance and decreased insulin sensitivity.

Seasonal dynamics of mobile carbohydrate pools in phloem and xylem of two alpine timberline conifers.

PubMed

Gruber, A; Pirkebner, D; Oberhuber, W

2013-10-01

Recent studies on non-structural carbohydrate (NSC) reserves in trees focused on xylem NSC reserves, while still little is known about changes in phloem carbohydrate pools, where NSC charging might be significantly different. To gain insight on NSC dynamics in xylem and phloem, we monitored NSC concentrations in stems and roots of Pinus cembra (L.) and Larix decidua (Mill.) growing at the alpine timberline throughout 2011. Species-specific differences affected tree phenology and carbon allocation during the course of the year. After a delayed start in spring, NSC concentrations in L. decidua were significantly higher in all sampled tissues from August until the end of growing season. In both species, NSC concentrations were five to seven times higher in phloem than that in xylem. However, significant correlations between xylem and phloem starch content found for both species indicate a close linkage between long-term carbon reserves in both tissues. In L. decidua also, free sugar concentrations in xylem and phloem were significantly correlated throughout the year, while a lack of correlation between xylem and phloem free sugar pools in P. cembra indicate a decline of phloem soluble carbohydrate pools during periods of high sink demand.

Seasonal dynamics of mobile carbohydrate pools in phloem and xylem of two alpine timberline conifers

PubMed Central

GRUBER, A.; PIRKEBNER, D.; OBERHUBER, W.

2016-01-01

Recent studies on non-structural carbohydrate (NSC) reserves in trees focused on xylem NSC reserves, while still little is known about changes in phloem carbohydrate pools, where NSC charging might be significantly different. To gain insight on NSC dynamics in xylem and phloem, we monitored NSC concentrations in stems and roots of Pinus cembra and Larix decidua growing at the alpine timberline throughout 2011. Species-specific differences affected tree phenology and carbon allocation in the course of the year. After a delayed start in spring, NSC concentrations in Larix decidua were significantly higher in all sampled tissues from August until end of growing season. In both species NSC concentrations were five to seven times higher in phloem than in xylem. However, significant correlations between xylem and phloem starch content found for both species indicate a close linkage between long term carbon reserves in both tissues. In Larix decidua also free sugar concentrations in xylem and phloem were significantly correlated throughout the year, while missing correlations between xylem and phloem free sugar pools in Pinus cembra indicate a decline of phloem soluble carbohydrate pools during periods of high sink demand. PMID:24186941

IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

PubMed

Al-Khan, A; Aye, I L; Barsoum, I; Borbely, A; Cebral, E; Cerchi, G; Clifton, V L; Collins, S; Cotechini, T; Davey, A; Flores-Martin, J; Fournier, T; Franchi, A M; Fretes, R E; Graham, C H; Godbole, G; Hansson, S R; Headley, P L; Ibarra, C; Jawerbaum, A; Kemmerling, U; Kudo, Y; Lala, P K; Lassance, L; Lewis, R M; Menkhorst, E; Morris, C; Nobuzane, T; Ramos, G; Rote, N; Saffery, R; Salafia, C; Sarr, D; Schneider, H; Sibley, C; Singh, A T; Sivasubramaniyam, T S; Soares, M J; Vaughan, O; Zamudio, S; Lash, G E

2011-03-01

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Among-tree variability and feedback effects result in different growth responses to climate change at the upper treeline in the Swiss Alps.

PubMed

Jochner, Matthias; Bugmann, Harald; Nötzli, Magdalena; Bigler, Christof

2017-10-01

Upper treeline ecotones are important life form boundaries and particularly sensitive to a warming climate. Changes in growth conditions at these ecotones have wide-ranging implications for the provision of ecosystem services in densely populated mountain regions like the European Alps. We quantify climate effects on short- and long-term tree growth responses, focusing on among-tree variability and potential feedback effects. Although among-tree variability is thought to be substantial, it has not been considered systematically yet in studies on growth-climate relationships. We compiled tree-ring data including almost 600 trees of major treeline species ( Larix decidua , Picea abies , Pinus cembra , and Pinus mugo ) from three climate regions of the Swiss Alps. We further acquired tree size distribution data using unmanned aerial vehicles. To account for among-tree variability, we employed information-theoretic model selections based on linear mixed-effects models (LMMs) with flexible choice of monthly temperature effects on growth. We isolated long-term trends in ring-width indices (RWI) in interaction with elevation. The LMMs revealed substantial amounts of previously unquantified among-tree variability, indicating different strategies of single trees regarding when and to what extent to invest assimilates into growth. Furthermore, the LMMs indicated strongly positive temperature effects on growth during short summer periods across all species, and significant contributions of fall ( L. decidua ) and current year's spring ( L. decidua , P. abies ). In the longer term, all species showed consistently positive RWI trends at highest elevations, but different patterns with decreasing elevation. L. decidua exhibited even negative RWI trends compared to the highest treeline sites, whereas P. abies , P. cembra , and P. mugo showed steeper or flatter trends with decreasing elevation. This does not only reflect effects of ameliorated climate conditions on tree growth over time, but also reveals first signs of long-suspected negative and positive feedback of climate change on stand dynamics at treeline.

Matrix metalloproteinase expression and activity in trophoblast-decidual tissues at organogenesis in CF-1 mouse.

PubMed

Fontana, Vanina; Coll, Tamara A; Sobarzo, Cristian M A; Tito, Leticia Perez; Calvo, Juan Carlos; Cebral, Elisa

2012-10-01

During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms. MMP-2 immunoreactivity was found in a granular and discrete pattern in ECM of mesometrial decidua (MD) near maternal blood vessels and slightly in non-decidualized endometrium (NDE). Immunoexpression of MMP-9 was also detected in NDE, in cytoplasm of decidual cells and ECM of vascular MD, in trophoblastic area and in growing antimesometrial deciduum. Gelatin zymography showed that MMP-9 activity was significantly lower in CM compared to the active form of direct (not cultured) and cultured decidua. The decidual active MMP-9 was significantly higher than the active MMP-2. These results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for MMP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation.

Immune cell and transcriptomic analysis of the human decidua in term and preterm parturition

PubMed Central

Rinaldi, S.F.; Makieva, S; Saunders, P.T.; Rossi, A.G.; Norman, J.E.

2017-01-01

Abstract STUDY QUESTION Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? SUMMARY ANSWER The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. WHAT IS KNOWN ALREADY Given its location, directly at the maternal–foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined. Using flow cytometry and microarray analysis, the present study aimed to investigate changes to the immune cell milieu of the decidua in association with the onset of parturition and define the decidual gene signature associated with term and preterm labour (PTL). STUDY DESIGN, SIZE, DURATION This study used decidual samples collected from 36 women across four clinical groups: term (38–42 weeks of gestation) not in labour, TNL; term in labour, TL; preterm (<35 weeks of gestation)not in labour, PTNL; and preterm in labour, PTL. PARTICIPANTS/MATERIALS, SETTING, METHODS Decidual lymphocytes were isolated from fresh decidual tissue collected from women in each of our four patient groups and stained with a panel of antibodies (CD45, CD3, CD19, CD56, CD4, CD8 and TCRVα24-Jα18) to investigate lymphocyte populations present in the decidua (TNL, n = 8; TL, n = 7; PTNL, n = 5; PTL, n = 5). RNA was extracted from decidual tissue and subjected to Illumina HT-12v4.0 BeadChip expression microarrays (TNL, n = 11; TL, n = 8; PTNL, n = 7; PTL, n = 10). Quantitative real-time PCR (qRT-PCR) was used to validate the microarray results. MAIN RESULTS AND THE ROLE OF CHANCE The relative proportions of decidual lymphocytes (T cells, NK cells, B cells and invariant natural killer (iNKT) cells) were unaffected by either gestation or labour status. However, we found elevated expression of the non-classical MHC-protein, CD1D, in PTL decidua samples (P < 0.05), suggesting the potential for increased activation of decidual invariant NKT (iNKT) cells in PTL. Both term and PTL were associated with widespread gene expression changes, particularly related to inflammatory signalling. Up-regulation of candidate genes in TL (IL-6, PTGS2, ATF3, IER3 and TNFAIP3) and PTL (CXCL8, MARCO, LILRA3 and PLAU) were confirmed by qRT-PCR analysis. LARGE SCALE DATA Microarray data are available at www.ebi.ac.uk/arrayexpress under accession number E-MTAB-5353. LIMITATIONS REASONS FOR CAUTION Whilst no changes in lymphocyte number were observed across our patient samples, we did not investigate the activation state of any of the immune cell sub-populations examined, therefore, it is possible that the function of these cells may be altered in association with labour onset. Additionally, the results of our transcriptomic analyses are descriptive and at this stage, we cannot prove direct causal link with the up-regulation of any of the genes examined and the onset of either term or PTL. WIDER IMPLICATIONS OF THE FINDINGS Our findings demonstrate that the onset of parturition is associated with widespread changes to the decidual transcriptome, and there are distinct gene expression changes associated with term and PTL. We confirmed that an inflammatory signature is present within the decidua, and we also report the up-regulation of several genes involved in regulating the inflammatory response. The identification of genes involved in regulating the inflammatory response may provide novel molecular targets for the development of new, more effective therapies for the prevention of preterm birth (PTB). Such targets are urgently required. STUDY FUNDING AND COMPETING INTEREST(S) This work was supported by Medical Research Council (grant number MR/L002657/1) and Tommy's, the baby charity. Jane Norman has had research grants from the charity Tommy's and from the National Institute for Health Research on PTB during the lifetime of this project. Jane Norman also sits on a data monitoring committee for GSK for a study on PTB prevention and her institution receives financial recompense for this. The other authors do not have any conflicts of interest to declare. PMID:28962035

Immunomodulatory activity of plant residues on ovine neutrophils.

PubMed

Farinacci, Maura; Colitti, Monica; Sgorlon, Sandy; Stefanon, Bruno

2008-11-15

Neutrophils play an essential role in host defense and inflammation. Plants have long been used to improve the immune function, but for most of them specific investigations on animal health are lacking. In the present study, water and hydroethanolic extracts from 11 plant wastes have been screened on immune responses of ovine neutrophils. Eight sheep clinically healthy, not lactating, non-pregnant were selected and used for the experiment. Freshly isolated neutrophils were incubated with the extracts of the residues at increasing doses, and then they were tested for adhesion and superoxide production induced with PMA. The residues of Larix decidua, Thymus vulgaris, Salix alba, Sinupret, Helianthus annuus, Mangifera indica modulated the neutrophil immune functions, moreover, Larix decidua, Thymus vulgaris and Salix alba presented the highest anti-inflammatory activity.

Nitric oxide synthase mRNA expression in human fetal membranes: a possible role in parturition.

PubMed

Dennes, W J; Slater, D M; Bennett, P R

1997-04-07

Nitric oxide (NO) is a potent endogenous smooth-muscle relaxant. It is synthesised from 1-arginine by isoforms of nitric oxide synthase (NOS). Whilst it is clear that the uterus responds to NO by relaxation, NOS expression has not been investigated in fetal membranes or myometrium in human pregnancy. This study has shown, using semi-quantitative RT-PCR, expression of cNOS mRNA in human amnion, chorion-decidua, and placenta. iNOS mRNA expression was demonstrated in human amnion, chorion-decidua, and placenta. It is possible that NO synthesised in fetal membranes may act either directly to inhibit myometrial contractility or indirectly to interact with other labour-associated genes, such as cyclo-oxygenase, to coordinate the onset of labour.

Placentation in Sigmodontinae: a rodent taxon native to South America

PubMed Central

2011-01-01

Background Sigmodontinae, known as "New World rats and mice," is a large subfamily of Cricetidae for which we herein provide the first comprehensive investigation of the placenta. Methods Placentas of various gestational ages ranging from early pregnancy to near term were obtained for five genera, i.e. Necromys, Euryoryzomys, Cerradomys, Hylaeamys, and Oligoryzomys. They were investigated by means of histology, immunohistochemistry, a proliferation marker, DBA-lectin staining and transmission electron microscopy. Results The chorioallantoic placenta was organized in a labyrinthine zone, spongy zone and decidua and an inverted yolk sac persisted until term. The chorioallantoic placenta was hemotrichorial. The interhemal barrier comprised fetal capillary endothelium and three layers of trophoblast, an outermost, cellular layer and two syncytial ones, with interspersed trophoblast giant cells (TGC). In addition, accumulations of TGC occurred below Reichert's membrane. The junctional zone contained syncytial trophoblast, proliferative cellular trophoblast, glycogen cells and TGC that were situated near to the maternal blood channels. In three of the genera, TGC were also accumulated in distinct areas at the placental periphery. PAS-positive glycogen cells derived from the junctional zone invaded the decidua. Abundant maternal uNK cells with positive response to PAS, vimentin and DBA-lectin were found in the decidua. The visceral yolk sac was completely inverted and villous. Conclusion The general aspect of the fetal membranes in Sigmodontinae resembled that found in other cricetid rodents. Compared to murid rodents there were larger numbers of giant cells and in some genera these were seen to congregate at the periphery of the placental disk. Glycogen cells were found to invade the decidua but we did not identify trophoblast in the walls of the deeper decidual arteries. In contrast these vessels were surrounded by large numbers of uNK cells. This survey of wild-trapped specimens from five genera is a useful starting point for the study of placentation in an important subfamily of South American rodents. We note, however, that some of these rodents can be captive bred and recommend that future studies focus on the study of time dated pregnancies. PMID:21518439

Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.

PubMed

Wang, Li-Qin; Yan, Xiao-Ting; Yan, Chun-Fang; Zhang, Xin-Wen; Hui, Ling-Yun; Xue, Mingzhan; Yu, Xue-Wen

2016-01-01

Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM). Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy. Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women. Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

Isolation and cellular properties of mesenchymal cells derived from the decidua of human term placenta.

PubMed

Kanematsu, Daisuke; Shofuda, Tomoko; Yamamoto, Atsuyo; Ban, Chiaki; Ueda, Takafumi; Yamasaki, Mami; Kanemura, Yonehiro

2011-09-01

The clinical promise of cell-based therapies is generally recognized, and has driven an intense search for good cell sources. In this study, we isolated plastic-adherent cells from human term decidua vera, called decidua-derived-mesenchymal cells (DMCs), and compared their properties with those of bone marrow-derived-mesenchymal stem cells (BM-MSCs). The DMCs strongly expressed the mesenchymal cell marker vimentin, but not cytokeratin 19 or HLA-G, and had a high proliferative potential. That is, they exhibited a typical fibroblast-like morphology for over 30 population doublings. Cells phenotypically identical to the DMCs were identified in the decidua vera, and genotyping confirmed that the DMCs were derived from the maternal components of the fetal adnexa. Flow cytometry analysis showed that the expression pattern of CD antigens on the DMCs was almost identical to that on BM-MSCs, but some DMCs expressed the CD45 antigen, and over 50% of them also expressed anti-fibroblast antigen. In vitro, the DMCs showed good differentiation into chondrocytes and moderate differentiation into adipocytes, but scant evidence of osteogenesis, compared with the BM-MSCs. Gene expression analysis showed that, compared with BM-MSCs, the DMCs expressed higher levels of TWIST2 and RUNX2 (which are associated with early mesenchymal development and/or proliferative capacity), several matrix metalloproteinases (MMP1, 3, 10, and 12), and cytokines (BMP2 and TGFB2), and lower levels of MSX2, interleukin 26, and HGF. Although DMCs did not show the full multipotency of BM-MSCs, their higher proliferative ability indicates that their cultivation would require less maintenance. Furthermore, the use of DMCs avoids the ethical concerns associated with the use of embryonic tissues, because they are derived from the maternal portion of the placenta, which is otherwise discarded. Thus, the unique properties of DMCs give them several advantages for clinical use, making them an interesting and attractive alternative to MSCs for regenerative medicine. 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Dendritic cells: key to fetal tolerance?

PubMed

Blois, Sandra M; Kammerer, Ulrike; Alba Soto, Catalina; Tometten, Mareike C; Shaikly, Valerie; Barrientos, Gabriela; Jurd, Richard; Rukavina, Daniel; Thomson, Angus W; Klapp, Burghard F; Fernández, Nelson; Arck, Petra C

2007-10-01

Pregnancy is a unique event in which a fetus, despite being genetically and immunologically different from the mother (a hemi-allograft), develops in the uterus. Successful pregnancy implies avoidance of rejection by the maternal immune system. Fetal and maternal immune cells come into direct contact at the decidua, which is a highly specialized mucous membrane that plays a key role in fetal tolerance. Uterine dendritic cells (DC) within the decidua have been implicated in pregnancy maintenance. DC serve as antigen-presenting cells with the unique ability to induce primary immune responses. Just as lymphocytes comprise different subsets, DC subsets have been identified that differentially control lymphocyte function. DC may also act to induce immunologic tolerance and regulation of T cell-mediated immunity. Current understanding of DC immunobiology within the context of mammalian fetal-maternal tolerance is reviewed and discussed herein.

CO2 enrichment alters diurnal stem radius fluctuations of 36-yr-old Larix decidua growing at the alpine tree line.

PubMed

Dawes, Melissa A; Zweifel, Roman; Dawes, Nicholas; Rixen, Christian; Hagedorn, Frank

2014-06-01

To understand how trees at high elevations might use water differently in the future, we investigated the effects of CO2 enrichment and soil warming (separately and combined) on the water relations of Larix decidua growing at the tree line in the Swiss Alps. We assessed diurnal stem radius fluctuations using point dendrometers and applied a hydraulic plant model using microclimate and soil water potential data as inputs. Trees exposed to CO2 enrichment for 9 yr showed smaller diurnal stem radius contractions (by 46 ± 16%) and expansions (42 ± 16%) compared with trees exposed to ambient CO2 . Additionally, there was a delay in the timing of daily maximum (40 ± 12 min) and minimum (63 ± 14 min) radius values for trees growing under elevated CO2 . Parameters optimized with the hydraulic model suggested that CO2 -enriched trees had an increased flow resistance between the xylem and bark, representing a more buffered water supply system. Soil warming did not alter diurnal fluctuation dynamics or the CO2 response. Elevated CO2 altered the hydraulic water flow and storage system within L. decidua trees, which might have contributed to enhanced growth during 9 yr of CO2 enrichment and could ultimately influence the future competitive ability of this key tree-line species. © 2014 WSL Institute for Snow and Avalanche Research - SLF. New Phytologist © 2014 New Phytologist Trust.

Vitamin D, the placenta and early pregnancy: effects on trophoblast function.

PubMed

Ganguly, Ankana; Tamblyn, Jennifer A; Finn-Sell, Sarah; Chan, Shiao-Y; Westwood, Melissa; Gupta, Janesh; Kilby, Mark D; Gross, Stephane R; Hewison, Martin

2018-02-01

Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH) 2 D). This appears to be due primarily to increased renal activity of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) that catalyzes synthesis of 1,25(OH) 2 D, but CYP27B1 expression is also prominent in both the maternal decidua and fetal trophoblast components of the placenta. The precise function of placental synthesis of 1,25(OH) 2 D remains unclear, but is likely to involve localized tissue-specific responses with both decidua and trophoblast also expressing the vitamin D receptor (VDR) for 1,25(OH) 2 D. We have previously described immunomodulatory responses to 1,25(OH) 2 D by diverse populations of VDR-expressing cells within the decidua. The aim of the current review is to detail the role of vitamin D in pregnancy from a trophoblast perspective, with particular emphasis on the potential role of 1,25(OH) 2 D as a regulator of trophoblast invasion in early pregnancy. Vitamin D deficiency is common in pregnant women, and a wide range of studies have linked low vitamin D status to adverse events in pregnancy. To date, most of these studies have focused on adverse events later in pregnancy, but the current review will explore the potential impact of vitamin D on early pregnancy, and how this may influence implantation and miscarriage. © 2018 Society for Endocrinology.

PPARγ Expression Is Diminished in Macrophages of Recurrent Miscarriage Placentas.

PubMed

Kolben, Theresa Maria; Rogatsch, Elisabeth; Vattai, Aurelia; Hester, Anna; Kuhn, Christina; Schmoeckel, Elisa; Mahner, Sven; Jeschke, Udo; Kolben, Thomas

2018-06-26

PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARγ under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARγ. Expression changes were evaluated by immunohistochemistry and real time PCR (RT-PCR) in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using cluster of differentiation 68 (CD68) as marker for macrophages and further characterized regarding their M1/M2 polarization status. The intermediate villous trophoblast revealed a significantly lower PPARγ expression in spontaneous and recurrent abortion. Maternal macrophages express PPARγ. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARγ only in very few cases. PPARγ is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARγ in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, D.A.; Chaput, A.; Tutton, D.

The mammalian fetus has been viewed as an unusually successful type of allograft and unexplained spontaneous abortion as a possible example of maternal rejection. Previous studies have shown the presence of small lymphocytic suppressor cells in the murine decidua which block the generation and reactivation of anti-paternal cytotoxic T lymphocytes (CTL) and lymphokine-activated killer cells (LAK) by elaborating a factor that inhibits the response to interleukin 2 (IL 2). A deficiency of these suppressor cells was associated with implants of xenogeneic Mus caroli embryos in the Mus musculus uterus which are infiltrated by maternal lymphoid cells and aborted. A deficiencymore » of such suppressor cells in the lymph nodes draining the uterus of CBA/J females in the process of aborting their semi-allogeneic CBA x DBA/2 F/sub 1/ progeny has also been shown. CBA/J females possess significantly lower levels of decidua-associated non-T suppressor cells on day 8.5 to 10.5 of allopregnancy than do mothers that will produce large litters of live babies. The F/sub 1/ embryos are infiltrated by maternal lymphocytes prior to abortion, and the infiltration and abortion rate appears to be augmented by pre-immunization with paternal DBA/2 spleen cells. The CBA/J x DBA/2J mating combination provides a model of spontaneous abortion in which immunologic factors play an important role and demonstrates that the association between deficiency of decidua-associated suppressor cells and xenopregnancy failure also holds true for the failure of allopregnancies resulting from natural within-species mating.« less

Mesenchymally-derived insulin-like growth factor 1 provides a paracrine stimulus for trophoblast migration.

PubMed

Lacey, Helen; Haigh, Teresa; Westwood, Melissa; Aplin, John D

2002-04-24

Trophoblast migration into maternal decidua is essential for normal pregnancy. It occurs in a defined time window, is spatially highly restricted, and is aberrant in some pathological pregnancies, but the control mechanisms are as yet ill-defined. At the periphery of the placenta, chorionic villi make contact with decidua to form specialised anchoring sites that feed interstitially migrating cytotrophoblast into the placental bed. Explants of first trimester mesenchymal villi on collagen type I developed cytotrophoblast outgrowths from the villous tips. However, in medium changed daily, cells did not progress to a migratory phenotype, remaining instead as a contiguous multi-layered sheet. This suggested the need for another migration stimulus. To test the possibility that this might arise from mesenchymal cells, serum-free conditioned medium from first trimester placental fibroblasts was added to explant cultures. Cytotrophoblasts were stimulated to migrate in streams across the gel. Affinity depletion of Insulin-like growth factor from fibroblast medium reduced streaming activity, while the addition of exogenous IGF-I (10 ng/ml) to serum-free medium produced a streaming phenotype. IGF receptor type 1 (IGFR1) was present on cells in the columns, and streaming could be inhibited by antibody to this receptor. IGF-II and activin, known stimulators of cytotrophoblast migration, were also active in this model. These data suggest a paracrine interaction between villous mesenchyme and the cytotrophoblast in anchoring sites that stimulates trophoblast infiltration of decidua. Such a signal would be self-limiting since it diminishes with distance from the placenta. This is a novel mechanism in placental development.

Reduced expressions of connexin 43 and VEGF in the first-trimester tissues from women with recurrent pregnancy loss.

PubMed

He, Xiaoping; Chen, Qinfang

2016-08-17

Approximately 45-50 % of the recurrent pregnancy loss (RPL) remain(s) unexplained that challenges its clinical management. Formation and development of placenta as well as angiogenesis are critical for successful pregnancy. Vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) play important roles in angiogenesis and placenta development and aberration of these have been linked to RPL. We aimed to investigate whether the expressions of VEGF and Cx43 were altered in the first-trimester tissues (chorionic villi and decidua) collected from women with RPL compared to those from healthy early pregnant women. First-trimester chorionic villi and decidua were collected from pregnant women diagnosed RPL who ended up with surgical intervention (n = 28) in comparison to those collected from women requesting surgical termination of their unwanted normal first-trimester pregnancies (n = 28). These two groups of women were matched in age and gestational weeks. Tissues were analyzed for the protein and messenger ribonucleic acid (mRNA) expressions of Cx43 and VEGF by immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expressions of both Cx43 and VEGF at the level of mRNA and protein in the villi and decidua from women with RPL were significantly decreased compared with those from women with normal early pregnancy. Reduction of Cx43 and VEGF expressed in the first-trimester tissues might indicate their important roles involved in RPL and thus holds the potential to develop pharmaceutical therapies for treatment of RPL.

Lack of photosynthetic or stomatal regulation after 9 years of elevated [CO2] and 4 years of soil warming in two conifer species at the alpine treeline.

PubMed

Streit, Kathrin; Siegwolf, Rolf T W; Hagedorn, Frank; Schaub, Marcus; Buchmann, Nina

2014-02-01

Alpine treelines are temperature-limited vegetation boundaries. Understanding the effects of elevated [CO2 ] and warming on CO2 and H2 O gas exchange may help predict responses of treelines to global change. We measured needle gas exchange of Larix decidua Mill. and Pinus mugo ssp. uncinata DC trees after 9 years of free air CO2 enrichment (575 µmol mol(-1) ) and 4 years of soil warming (+4 °C) and analysed δ(13) C and δ(18) O values of needles and tree rings. Tree needles under elevated [CO2 ] showed neither nitrogen limitation nor end-product inhibition, and no down-regulation of maximal photosynthetic rate (Amax ) was found. Both tree species showed increased net photosynthetic rates (An ) under elevated [CO2 ] (L. decidua: +39%; P. mugo: +35%). Stomatal conductance (gH2O ) was insensitive to changes in [CO2 ], thus transpiration rates remained unchanged and intrinsic water-use efficiency (iWUE) increased due to higher An . Soil warming affected neither An nor gH2O . Unresponsiveness of gH2O to [CO2 ] and warming was confirmed by δ(18) O needle and tree ring values. Consequently, under sufficient water supply, elevated [CO2 ] induced sustained enhancement in An and lead to increased C inputs into this ecosystem, while soil warming hardly affected gas exchange of L. decidua and P. mugo at the alpine treeline. © 2013 John Wiley & Sons Ltd.

Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells

PubMed Central

Shofuda, Tomoko; Kanematsu, Daisuke; Fukusumi, Hayato; Yamamoto, Atsuyo; Bamba, Yohei; Yoshitatsu, Sumiko; Suemizu, Hiroshi; Nakamura, Masato; Sugimoto, Yoshikazu; Furue, Miho Kusuda; Kohara, Arihiro; Akamatsu, Wado; Okada, Yohei; Okano, Hideyuki; Yamasaki, Mami; Kanemura, Yonehiro

2013-01-01

Placental tissue is a biomaterial with remarkable potential for use in regenerative medicine. It has a three-layer structure derived from the fetus (amnion and chorion) and the mother (decidua), and it contains huge numbers of cells. Moreover, placental tissue can be collected without any physical danger to the donor and can be matched with a variety of HLA types. The decidua-derived mesenchymal cells (DMCs) are highly proliferative fibroblast-like cells that express a similar pattern of CD antigens as bone marrow-derived mesenchymal cells (BM-MSCs). Here we demonstrated that induced pluripotent stem (iPS) cells could be efficiently generated from DMCs by retroviral transfer of reprogramming factor genes. DMC-hiPS cells showed equivalent characteristics to human embryonic stem cells (hESCs) in colony morphology, global gene expression profile (including human pluripotent stem cell markers), DNA methylation status of the OCT3/4 and NANOG promoters, and ability to differentiate into components of the three germ layers in vitro and in vivo. The RNA expression of XIST and the methylation status of its promoter region suggested that DMC-iPSCs, when maintained undifferentiated and pluripotent, had three distinct states: (1) complete X-chromosome reactivation, (2) one inactive X-chromosome, or (3) an epigenetic aberration. Because DMCs are derived from the maternal portion of the placenta, they can be collected with the full consent of the adult donor and have considerable ethical advantages for cell banking and the subsequent generation of human iPS cells for regenerative applications. PMID:26858858

Comparison of human mesenchymal stromal cells from four neonatal tissues: Amniotic membrane, chorionic membrane, placental decidua and umbilical cord.

PubMed

Araújo, Anelise Bergmann; Salton, Gabrielle Dias; Furlan, Juliana Monteiro; Schneider, Natália; Angeli, Melissa Helena; Laureano, Álvaro Macedo; Silla, Lúcia; Passos, Eduardo Pandolfi; Paz, Ana Helena

2017-05-01

Mesenchymal stromal cells (MSCs) are being investigated as a potential alternative for cellular therapy. This study was designed to compare the biological characteristics of MSCs isolated from amniotic membrane (A-MSCs), chorionic membrane (C-MSCs), placental decidua (D-MSCs) and umbilical cord (UC-MSCs) to ascertain whether any one of these sources is superior to the others for cellular therapy purposes. MSCs were isolated from amniotic membrane, chorionic membrane, umbilical cord and placental decidua. Immunophenotype, differentiation ability, cell size, cell complexity, polarity index and growth kinetics of MSCs isolated from these four sources were analyzed. MSCs were successfully isolated from all four sources. Surface marker profile and differentiation ability were consistent with human MSCs. C-MSCs in suspension were the smallest cells, whereas UC-MSCs presented the greatest length and least width. A-MSCs had the lowest polarity index and UC-MSCs, as more elongated cells, the highest. C-MSCs, D-MSCs and UC-MSCs exhibited similar growth capacity until passage 8 (P8); C-MSCs presented better lifespan, whereas insignificant proliferation was observed in A-MSCs. Neonatal and maternal tissues can serve as sources of multipotent stem cells. Some characteristics of MSCs obtained from four neonatal tissues were compared and differences were observed. Amniotic membrane was the least useful source of MSCs, whereas chorionic membrane and umbilical cord were considered good options for future use in cell therapy because of the known advantages of immature cells. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

NODAL in the Uterus Is Necessary for Proper Placental Development and Maintenance of Pregnancy1

PubMed Central

Park, Craig B.; DeMayo, Francesco J.; Lydon, John P.; Dufort, Daniel

2012-01-01

Preterm birth is the single leading cause of perinatal mortality in developed countries, affecting approximately 12% of pregnancies and accounting for 75% of neonatal loss in the United States. Despite the prevalence and severity of premature delivery, the causes and mechanisms that underlie spontaneous and idiopathic preterm birth remain unknown. Our inability to elucidate these fundamental causes has been attributed to a poor understanding of the signaling pathways associated with the premature induction of parturition and a lack of suitable animal models available for preterm birth research. In this study, we describe the generation and analysis of a novel conditional knockout of the transforming growth factor beta (TGFB) superfamily member, Nodal, from the maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females exhibited a severe malformation of the maternal decidua basalis during placentation, leading to significant intrauterine growth restriction, and ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several approaches, we characterized aberrant placental development and demonstrated that reduced proliferation combined with increased apoptosis resulted in a diminished decidua basalis and compromised maternal-fetal interface. Last, we evaluated various components of the established parturition cascade and determined that preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX-2) upregulation at the placental interface. Taken together, the results presented in this study highlight an in vivo role for maternal NODAL during placentation, present an interesting link between disrupted decidua basalis formation and premature parturition, and describe a potentially valuable model toward elucidating the complex processes that underlie preterm birth. PMID:22378764

Expression of {beta}{sub 1} integrins in human endometrial stromal and decidual cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiokawa, Shigetatsu; Yoshimura, Yasunori; Nakamura, Yukio

The present study was undertaken to investigate the expression of {beta}{sub 1} integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, and {alpha}{sub 5} subunits of the {beta}{sub 1} integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E{sub 2}) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of {beta}{sub 1} integrins in vitro. Flow cytometry also demonstrated the expression of themore » {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, {alpha}{sub 3}, {alpha}{sub 5}, and {alpha}{sub 6} subunits of {beta}{sub 1} integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of {beta}{sub 1} integrins expression. Immunohistochemistry confirmed the {beta}{sub 1} integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed {beta}{sub 1} integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, {beta}{sub 1} integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation. 43 refs., 7 figs., 2 tabs.« less

Acute Fetal Demise with First Trimester Maternal Infection Resulting from Listeria monocytogenes in a Nonhuman Primate Model

PubMed Central

Wolfe, Bryce; Wiepz, Gregory J.; Schotzko, Michele; Bondarenko, Gennadiy I.; Durning, Maureen; Simmons, Heather A.; Mejia, Andres; Faith, Nancy G.; Sampene, Emmanuel; Suresh, Marulasiddappa; Kathariou, Sophia; Czuprynski, Charles J.

2017-01-01

ABSTRACT Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques (Macaca fascicularis) received a single intragastric inoculation between days 36 and 46 of gestation with 107 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy. PMID:28223455

Research on the expression of integrin β3 and leukaemia inhibitory factor in the decidua of women with cesarean scar pregnancy.

PubMed

Qian, Zhi-Da; Weng, Yue; Wang, Chun-Fen; Huang, Li-Li; Zhu, Xiao-Ming

2017-03-11

Cesarean scar pregnancy (CSP) is a late serious complication of cesarean section. There has been an increase in the incidence of CSP worldwide in recent years. It's a life-threatening condition because of the high risk of uncontrolled hemorrhage and uterine rupture. The mechanism of CSP is still unclear. The endometrial receptivity might be different in the cesarean scar between CSP and normal pregnancies. Endometrial expression of integrin β3 and LIF positively correlates with endometrial receptivity and embryo implantation. The purpose of the study is to explore the mechanism of CSP. The EnVision two-step immunohistochemical staining technique was used to detect the expression of integrin β3 and LIF in the decidua of women with CSP (20 cases) and normal pregnancies (20 cases). The distribution and staining intensity of integrin β3 and LIF in the two groups were observed. Observation of the staining were done using microscope within five randomly selected high-power fields (HPF, 10 × 40). All data analyses were conducted with SPSS 17.0 and the statistical significance was set at P <0.05. The decidua in the different parts of both two groups that stained with the anti-integrin β3 and anti-LIF antibody: most of the integrin β3 and LIF positive cells were located in glandular epithelium. The expression intensity of integrin β3 in the cesarean scar in CSP group was significant higher than the uterine cavity in CSP group and the cesarean scar in normal pregnancy group. It's similar with the uterine cavity in normal pregnancy group. The expression intensity of LIF in the cesarean scar in CSP group was significant higher than the uterine cavity in CSP group and the cesarean scar in normal pregnancy group. It's significant lower than the uterine cavity in normal pregnancy group. The decidual integrin β3 and LIF might play an important role in the mechanism of CSP. The increase expression of integrin β3 and LIF in the cesarean scar decidua might be associated with embryo implantation in cesarean scar. The occurrence of CSP might be related to the changes of endometrial receptivity in local cesarean scar.

Decreased expression of the vitamin D receptor in women with recurrent pregnancy loss.

PubMed

Yan, Xiaoting; Wang, Liqin; Yan, Chunfang; Zhang, Xinwen; Hui, Lingyun; Sheng, Qiu; Xue, Mingzhan; Yu, Xuewen

2016-09-15

The multiple functions of vitamin D3 have stimulated interest in the role that this vitamin may play during pregnancy. The present study investigated the expression of the vitamin D receptor (VDR) in women during the first trimester of pregnancy in order to determine whether VDR is associated with recurrent pregnancy loss (RPL). Forty women at 7-10 weeks gestation with RPL and 40 women of similar gestational age with a healthy pregnancy were recruited. VDR mRNA and protein in chorionic villi and decidua were evaluated by immunohistochemistry, confocal laser scanning microscopy (CLSM), western blot, and quantitative real-time polymerase chain reaction. The serum levels of VDR were measured by an enzyme-linked immunosorbent assay. Women with RPL had a significantly weaker expression of VDR mRNA in villi and decidual tissues compared with the control women (both p < 0.0001). Western blot analysis showed an approximately 46% decrease in VDR expression in villi and a 52% decrease in decidua in the RPL vs. the controls. Serum VDR levels were also significantly lower in the RPL group than in the control group (p = 0.003). Compared with the controls, immunohistochemical and CLSM analysis revealed significantly lower VDR expression in villous cytotrophoblasts and stromal cells, as well as in decidual glandular epithelial and stromal cells (all p < 0.05). In conclusion, these observations show that women with RPL have lower levels of VDR expression in chorionic villi, decidua and serum compared with normal pregnant women, suggesting that decreased VDR expression in the first trimester pregnancy may be associated with RPL. Copyright © 2016 Elsevier Inc. All rights reserved.

G protein-coupled estrogen receptor 1 (GPER, GPR 30) in normal human endometrium and early pregnancy decidua.

PubMed

Kolkova, Z; Noskova, V; Ehinger, A; Hansson, S; Casslén, B

2010-10-01

The recently identified trans-membrane G protein-coupled estrogen receptor 1 (GPER, GPR30) has been implicated in rapid non-genomic effects of estrogens. This focuses on expression and localization of GPER mRNA and protein in normal cyclic endometrium and early pregnancy decidua. Real-time PCR, western blotting, in situ hybridization and immuno-histochemistry were used. Endometrial expression of GPER mRNA was lower in the secretory phase than in the proliferative phase, and even lower in the decidua. The expression pattern was similar to that of ERα mRNA, but different from that of ERβ mRNA. Western blot detected GPER protein as a 54 kDa band in all endometrial and decidual samples. In contrast to the mRNA, GPER protein did not show cyclic variations. Apparently, a lower amount of mRNA is sufficient to maintain protein levels in the secretory phase. GPER mRNA was predominantly localized in the epithelium of mid- and late-proliferative phase endometrium, whereas expression in early proliferative and secretory glands could not be distinguished from the diffuse stromal signal, which was present throughout the cycle. Immuno-staining for GPER was stronger in glandular and luminal epithelium than in the stroma throughout the cycle. The cyclic variations of GPER mRNA obviously relate to strong epithelial expression in the proliferative phase, and the expression pattern suggests regulation by ovarian steroids. GPER protein is present in endometrial tissue throughout the cycle, and the epithelial localization suggests potential functions during sperm migration at mid-cycle, as well as decidualization and blastocyst implantation in the mid-secretory phase.

Xylem and phloem phenology in co-occurring conifers exposed to drought.

PubMed

Swidrak, Irene; Gruber, Andreas; Oberhuber, Walter

2014-01-01

Variability in xylem and phloem phenology among years and species is caused by contrasting temperatures prevailing at the start of the growing season and species-specific sensitivity to drought. The focus of this study was to determine temporal dynamics of xylem and phloem formation in co-occurring deciduous and evergreen coniferous species in a dry inner Alpine environment (750 m a.s.l., Tyrol, Austria). By repeated micro-sampling of the stem, timing of key phenological dates of xylem and phloem formation was compared among mature Pinus sylvestris , Larix decidua and Picea abies during two consecutive years. Xylem formation in P. sylvestris started in mid and late April 2011 and 2012, respectively, and in both years about 2 week later in P. abies and L. decidua . Phloem formation preceded xylem formation on average by 3 week in P. sylvestris , and c . 5 week in P. abies and L. decidua . Based on modeled cell number increase, tracheid production peaked between early through late May 2011 and late May through mid-June 2012. Phloem formation culminated between late April and mid-May in 2011 and in late May 2012. Production of xylem and phloem cells continued for about 4 and 5-6 months, respectively. High variability in xylem increment among years and species is related to exogenous control by climatic factors and species-specific sensitivity to drought, respectively. On the other hand, production of phloem cells was quite homogenous and showed asymptotic decrease with respect to xylem cells indicating endogenous control. Results indicate that onset and culmination of xylem and phloem formation are controlled by early spring temperature, whereby strikingly advanced production of phloem compared to xylem cells suggests lower temperature requirement for initiation of the former.

Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development

PubMed Central

Peng, Jia; Monsivais, Diana; You, Ran; Zhong, Hua; Pangas, Stephanie A.; Matzuk, Martin M.

2015-01-01

Members of the transforming growth factor β (TGF-β) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-β signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-β subfamily. Absence of ALK5 leads to early embryonic lethality because of severe defects in vascular development. In this study, we conditionally ablated uterine ALK5 using progesterone receptor-cre mice to define the physiological roles of ALK5 in female reproduction. Despite normal ovarian functions and artificial decidualization in conditional knockout (cKO) mice, absence of uterine ALK5 resulted in substantially reduced female reproduction due to abnormalities observed at different stages of pregnancy, including implantation defects, disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells, and impairment of spiral artery remodeling. In our microarray analysis, genes encoding proteins involved in cytokine–cytokine receptor interactions and NK cell-mediated cytotoxicity were down-regulated in cKO decidua compared with control decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus control decidua. According to these data, we hypothesize that TGF-β acts on decidual cells via ALK5 to induce expression of other growth factors and cytokines, which are key regulators in luminal epithelium proliferation, trophoblast development, and uNK maturation during pregnancy. Our findings not only generate a mouse model to study TGF-β signaling in female reproduction but also shed light on the pathogenesis of many pregnancy complications in human, such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction. PMID:26305969

Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads.

PubMed

Hurtado, Christine Waasdorp; Golden-Mason, Lucy; Brocato, Megan; Krull, Mona; Narkewicz, Michael R; Rosen, Hugo R

2010-08-30

Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.

Three-dimensional analysis of the anatomical growth response of European conifers to mechanical disturbance.

PubMed

Schneuwly, Dominique M; Stoffel, Markus; Dorren, Luuk K A; Berger, Frédéric

2009-10-01

Studies on tree reaction after wounding were so far based on artificial wounding or chemical treatment. For the first time, type, spread and intensity of anatomical responses were analyzed and quantified in naturally disturbed Larix decidua Mill., Picea abies (L.) Karst. and Abies alba Mill. trees. The consequences of rockfall impacts on increment growth were assessed at the height of the wounds, as well as above and below the injuries. A total of 16 trees were selected on rockfall slopes, and growth responses following 54 wounding events were analyzed on 820 cross-sections. Anatomical analysis focused on the occurrence of tangential rows of traumatic resin ducts (TRD) and on the formation of reaction wood. Following mechanical disturbance, TRD production was observed in 100% of L. decidua and P. abies wounds. The radial extension of TRD was largest at wound height, and they occurred more commonly above, rather than below, the wounds. For all species, an intra-annual radial shift of TRD was observed with increasing axial distance from wounds. Reaction wood was formed in 87.5% of A. alba following wounding, but such cases occurred only in 7.7% of L. decidua. The results demonstrate that anatomical growth responses following natural mechanical disturbance differ significantly from the reactions induced by artificial stimuli or by decapitation. While the types of reactions remain comparable between the species, their intensity, spread and persistence disagree considerably. We also illustrate that the external appearance of wounds does not reflect an internal response intensity. This study reveals that disturbance induced under natural conditions triggers more intense and more widespread anatomical responses than that induced under artificial stimuli, and that experimental laboratory tests considerably underestimate tree response.

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway.

PubMed

Cook, Ian H; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O; Sales, Kurt J; Jabbour, Henry N

2010-03-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1-prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1-PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium-calcineurin signalling pathway in a guanine nucleotide-binding protein (G(q/11)), extracellular signal-regulated kinases, Ca(2+) and calcineurin-nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Ralpha and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1-PROKR1 signalling pathway regulating IL-11.

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway

PubMed Central

Cook, Ian H.; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O.; Sales, Kurt J.; Jabbour, Henry N.

2010-01-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1–prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1–PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium–calcineurin signalling pathway in a guanine nucleotide-binding protein (Gq/11), extracellular signal-regulated kinases, Ca2+ and calcineurin–nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Rα and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1–PROKR1 signalling pathway regulating IL-11. PMID:19801577

Number of decidual natural killer cells & macrophages in pre-eclampsia

PubMed Central

Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Popovic, Jasmina; Tasic, Marija; Stojnev, Slavica

2016-01-01

Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK) cells and macrophages in the decidua. Methods: This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56+ NK cells, CD68+ macrophages and cytokeratin 7 trophoblastic cells. Results: In pre-eclampsia, there was a significantly lower number of CD56+ NK cells in the decidua (P<0.001) and a higher number of CD68+ macrophages (P<0.001) compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR), a significantly greater number of NK cells (P<0.05) was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56+ NK cells were significantly less (P<0.05) and macrophages were more (P<0.05) in the group with poor trophoblastic invasion. Interpretation & conclusions: Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed. PMID:28474619

Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss.

PubMed

Krieg, S A; Fan, X; Hong, Y; Sang, Q-X; Giaccia, A; Westphal, L M; Lathi, R B; Krieg, A J; Nayak, N R

2012-09-01

Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

Bud gall midges - potential invaders on larches in North America

Treesearch

Yuri N. Baranchikov

2007-01-01

Larch bud gall midges (Diptera: Cecidomyiidae) form a specialized group of gall insects inhabiting buds of larch (Larix) in the northern Palaearctic Region. Currently there are four described species in this group. Dasineura kellneri Henschel is found in Central Europe and infests Larix decidua; D....

Screening larch in vitro for resistance to Mycosphaerella laricina

Treesearch

M.E. Ostry; Paula M. Pijut; D.D. Skilling

1991-01-01

Needle blight of larch caused by Mycosphaerella laricina seriously limits the productivity of susceptible trees in the north central and northeastern United States. Adventitious shoots, derived from cotyledon tissue culture, of selected European larch (Larix decidua) and a hybrid larch were inoculated in vitro with three isolates...

Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers.

PubMed

Macias, Maria I; Grande, Jesús; Moreno, Ana; Domínguez, Irene; Bornstein, Rafael; Flores, Ana I

2010-11-01

The objective of the study was to isolate and characterize a population of mesenchymal stem cells (MSCs) from human term placental membranes. We isolated an adherent cell population from extraembryonic membranes. Morphology, phenotype, growth characteristics, karyotype, and immunological and differentiation properties were analyzed. The isolated placental MSCs were from maternal origin and named as decidua-derived mesenchymal stem cells (DMSCs). DMSCs differentiated into derivatives of all germ layers. It is the first report about placental MSC differentiation into alveolar type II cells. Clonally expanded DMSCs differentiated into all embryonic layers, including pulmonary cells. DMSCs showed higher life span than placental cells from fetal origin and proliferated without genomic instability. The data suggest that DMSCs are true multipotent MSCs, distinguishing them from other placental MSCs. DMSCs could be safely used in the mother as a potential source of MSCs for pelvic floor dysfunctions and immunological diseases. Additionally, frozen DMSCs can be stored for both autologous and allogeneic tissue regeneration. Copyright © 2010 Mosby, Inc. All rights reserved.

Micropropagation of Capparis decidua (Forsk.) Edgew. - a tree of arid horticulture.

PubMed

Deora, N S; Shekhawat, N S

1995-12-01

A method for micropropagation of mature trees of Capparis decidua was developed. Multiple shoots were obtained from nodal explants on Murashige and Skoog's (1962) medium+0.1mgl(-1) NAA+5.0mgl(-1)BAP+additives (50mgl(-1) ascorbic acid and25 mgl(-1) each of adenine sulphate, L-arginine and citric acid) at 28 ± 2°C, 12 h/dphotoperiod and 35-40 μmol m(-2)s(-1) photon flux density. The shoots were multiplied by (i) subculture of nodal shoot segments onto MS +0.1 mgl(--1) IAA+1.0mgl(-1) BAPH+additives, and (ii) repeated transfer of original explant onto MS+ 0.1mgl(-1) IAA+mg l(-1) BAP+additives, at intervals of 3 weeks. Sixty to 70% of the shoots rooted when pulse treated with 100 mg l(-1) IBA in half strength MS liquid medium for 4h, and then transferred onto hormone-free half-strength agar-gelled MS basal saltmedium. Incubation in dark at 33 ± 2°C for 6d favoured root induction. In vitro hardened plants were transferred to pots.

In Vitro Dermo-Cosmetic Evaluation of Bark Extracts from Common Temperate Trees.

PubMed

Hubert, Jane; Angelis, Apostolis; Aligiannis, Nektarios; Rosalia, Michalea; Abedini, Amin; Bakiri, Ali; Reynaud, Romain; Nuzillard, Jean-Marc; Gangloff, Sophie C; Skaltsounis, Alexios-Leandros; Renault, Jean-Hugues

2016-10-01

Wood residues produced from forestry activities represent an interesting source of biologically active, high value-added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies , and Populus tremula after three successive solid/liquid extractions of the barks with n- heptane, methanol, and methanol/water. All extracts were evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against gram-positive Staphylococcus aureus . In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua , and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermo-cosmetic industry. Georg Thieme Verlag KG Stuttgart · New York.

Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

PubMed

Davila, Juanmahel; Laws, Mary J; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

2015-08-01

During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal-endothelial and stromal-trophoblast crosstalk critical for placenta development and establishment of pregnancy.

Localisation pattern of homogalacturonan and arabinogalactan proteins in developing ovules of the gymnosperm plant Larix decidua Mill.

PubMed

Rafińska, Katarzyna; Bednarska, Elżbieta

2011-03-01

We have identified and characterised the temporal and spatial distribution of the homogalacturonan (HG) and arabinogalactan proteins (AGP) epitopes that are recognised by the antibodies JIM5, JIM7, LM2, JIM4, JIM8 and JIM13 during ovule differentiation in Larix decidua Mill. The results obtained clearly show differences in the pattern of localisation of specific HG epitopes between generative and somatic cells of the ovule. Immunocytochemical studies revealed that the presence of low-esterified HG is characteristic only of the wall of megasporocyte and megaspores. In maturing female gametophytes, highly esterified HG was the main form present, and the central vacuole of free nuclear gametophytes was particularly rich in this category of HG. This pool will probably be used in cell wall building during cellularisation. The selective labelling obtained with AGP antibodies indicates that some AGPs can be used as markers for gametophytic and sporophytic cells differentiation. Our results demonstrated that the AGPs recognised by JIM4 may constitute molecules determining changes in ovule cell development programs. Just after the end of meiosis, the signal detected with JIM4 labelling appeared only in functional and degenerating megaspores. This suggests that the antigens bound by JIM4 are involved in the initiation of female gametogenesis in L. decidua. Moreover, the analysis of AGPs distribution showed that differentiation of the nucellus cells occurs in the very young ovule stage before megasporogenesis. Throughout the period of ovule development, the pattern of localisation of the studied AGPs was different both in tapetum cells surrounding the gametophyte and in nucellus cells. Changes in the distribution of AGPs were also observed in the nucellus of the mature ovule, and they could represent an indicator of tissue arrangement to interact with the growing pollen tube. The possible role of AGPs in fertilisation is also discussed.

Soil Properties Related to Coniferous Seedling Height Growth in Northern Wisconsin

Treesearch

John J. Rawinski; James A. Bowles; Nonan V. Noste

1980-01-01

Soil properties (organic matter content, pH, texture, and microclimate) were related to early height growth of jack pine (Pinus banksiana, Lamb.), red pine (Pinus resinosa, Ait.), white spruce (Picea glauca, (Moench) Voss), and hybrid larch (Larix leptolepis x Larizx decidua) planted in northern Wisconsin. Based on 2-year height growth, jack pine and hybrid larch...

Ecological Baseline, Fort Hood, Texas

DTIC Science & Technology

1980-08-01

cedar eTm (Uiimus crassifolia), Texas ash (Fraxinus texansis), and Texas persimmon ( Diospyros texana). Conversely, the two predominant tree species...Ilex decidua), Mex- ican buckeye (Ungnadia spjeciosa), and Texas persimmon ( Diospyros texana). Vines included greenbrier (Smilax bona-nox) and white...Hedgehey Cactus (Echinocereus sp.) has been observed on Fort Hood. Due to the brief period of flowering for this genus , the individual species were not

Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages.

PubMed

Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

2016-04-28

Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas.

Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages

PubMed Central

Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

2016-01-01

Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas. PMID:27136536

Traditional plants used for the treatment of diabetes mellitus in Sursagar constituency, Jodhpur, Rajasthan - An ethnomedicinal survey.

PubMed

Goyal, Manoj

2015-11-04

In Jodhpur, large number of people suffering with non-insulin dependent diabetes mellitus (type 2 diabetes). They are using medicinal plants along with modern medicine for the management of diabetes. The aim of this work is to document the anti-diabetic plants and determine the most relevant anti-diabetic plant species using the Disease Consensus Index. Ethnomedicinal survey was conducted for selection of anti-diabetic plant. Structured questionnaire was developed for calculation of Disease Consensus Index and administered to fifty Type 2 diabetic patients for recording their response. Twenty-one species of anti-diabetic plants were recorded, Momordica charantia (score: 0.71), Azadirachta indica (score: 0.64), Trigonella foenum-graecum (score: 0.63), Capparis decidua (score: 0.60), Withania coagulans (score: 0.54), Gymnema sylvestre (score: 0.52) and Syzygium cumini (score: 0.51) were the most significant anti-diabetic plants of the area of study, having DCI more than 0.5. Use of anti-diabetic plants is prevalent diabetic patients of the area. C. decidua, W. coagulans and G. sylvestre are recommend the further phytochemical and pharmacological investigation due to high DCI score and relatively unexplored status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Two-way regulation between cells and aligned collagen fibrils: local 3D matrix formation and accelerated neural differentiation of human decidua parietalis placental stem cells.

PubMed

Li, Wen; Zhu, Bofan; Strakova, Zuzana; Wang, Rong

2014-08-08

It has been well established that an aligned matrix provides structural and signaling cues to guide cell polarization and cell fate decision. However, the modulation role of cells in matrix remodeling and the feedforward effect on stem cell differentiation have not been studied extensively. In this study, we report on the concerted changes of human decidua parietalis placental stem cells (hdpPSCs) and the highly ordered collagen fibril matrix in response to cell-matrix interaction. With high-resolution imaging, we found the hdpPSCs interacted with the matrix by deforming the cell shape, harvesting the nearby collagen fibrils, and reorganizing the fibrils around the cell body to transform a 2D matrix to a localized 3D matrix. Such a unique 3D matrix prompted high expression of β-1 integrin around the cell body that mediates and facilitates the stem cell differentiation toward neural cells. The study offers insights into the coordinated, dynamic changes at the cell-matrix interface and elucidates cell modulation of its matrix to establish structural and biochemical cues for effective cell growth and differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

PubMed Central

El-Azzamy, Haidy; Balogh, Andrea; Romero, Roberto; Xu, Yi; LaJeunesse, Christopher; Plazyo, Olesya; Xu, Zhonghui; Price, Theodore G.; Dong, Zhong; Tarca, Adi L.; Papp, Zoltan; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Kim, Chong Jai; Gomez-Lopez, Nardhy; Than, Nandor Gabor

2017-01-01

Background The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. Methods Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. Results The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. Conclusions Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition. PMID:28226203

Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

PubMed

Giudice, L C; Irwin, J C

1999-01-01

The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

Stable Water Use Efficiency under Climate Change of Three Sympatric Conifer Species at the Alpine Treeline.

PubMed

Wieser, Gerhard; Oberhuber, Walter; Gruber, Andreas; Leo, Marco; Matyssek, Rainer; Grams, Thorsten Erhard Edgar

2016-01-01

The ability of treeline associated conifers in the Central Alps to cope with recent climate warming and increasing CO2 concentration is still poorly understood. We determined tree ring stable carbon and oxygen isotope ratios of Pinus cembra, Picea abies, and Larix decidua trees from 1975 to 2010. Stable isotope ratios were compared with leaf level gas exchange measurements carried out in situ between 1979 and 2007. Results indicate that tree ring derived intrinsic water-use efficiency (iWUE) of P. cembra, P. abies and L. decidua remained constant during the last 36 years despite climate warming and rising atmospheric CO2. Temporal patterns in Δ(13)C and Δ(18)O mirrored leaf level gas exchange assessments, suggesting parallel increases of CO2-fixation and stomatal conductance of treeline conifer species. As at the study site soil water availability was not a limiting factor iWUE remained largely stable throughout the study period. The stability in iWUE was accompanied by an increase in basal area increment (BAI) suggesting that treeline trees benefit from both recent climate warming and CO2 fertilization. Finally, our results suggest that iWUE may not change species composition at treeline in the Austrian Alps due to similar ecophysiological responses to climatic changes of the three sympatric study species.

Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.

PubMed

Ball, E; Robson, S C; Ayis, S; Lyall, F; Bulmer, J N

2006-03-01

Invasion by extravillous trophoblast of uterine decidua and myometrium and the associated spiral artery 'transformation' are essential for the development of normal pregnancy. Small pilot studies of placental bed and basal plate tissues from miscarriages have suggested that impaired interstitial and endovascular trophoblast invasion may play a role in the pathogenesis of miscarriage. The hypothesis that early miscarriage is associated with reduced extravillous trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium and at least one spiral artery from early, karyotyped embryonic miscarriages (

H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition

PubMed Central

Nancy, Patrice; Siewiera, Johan; Tagliani, Elisa; Osokine, Ivan; Manandhar, Priyanka; Clementi, Caterina

2017-01-01

Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a noncontractile state until term and then surmounts this state to enter labor. Here, we show that dynamic generation and erasure of the repressive histone modification tri-methyl histone H3 lysine 27 (H3K27me3) in decidual stromal cells dictate both elements of pregnancy success in mice. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets ensured uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and most unexpectedly, generating myofibroblasts and associated wound-healing responses. In late gestation, genome-wide H3K27 demethylation allowed for target gene upregulation, decidual activation, and labor entry. Pharmacological inhibition of H3K27 demethylation in late gestation not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a noninflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders. PMID:29202469

Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

PubMed Central

Vallejo, Griselda; Maschi, Darío; Citrinovitz, Ana Cecilia Mestre; Aiba, Kazuhiro; Maronna, Ricardo; Yohai, Victor; Ko, Minoru S. H.; Beato, Miguel; Saragüeta, Patricia

2009-01-01

During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3 fold, FDR > 0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells. PMID:19780023

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion.

PubMed

Li, Jing; Li, Fan-fan; Zuo, Wei; Zhou, Yuan; Hao, Hai-yan; Dang, Jing; Jiang, Min; He, Meng-zhou; Deng, Dong-rui

2014-08-01

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Uterine DCs are crucial for decidua formation during embryo implantation in mice

PubMed Central

Plaks, Vicki; Birnberg, Tal; Berkutzki, Tamara; Sela, Shay; BenYashar, Adi; Kalchenko, Vyacheslav; Mor, Gil; Keshet, Eli; Dekel, Nava; Neeman, Michal; Jung, Steffen

2008-01-01

Implantation is a key stage during pregnancy, as the fate of the embryo is often decided upon its first contact with the maternal endometrium. Around this time, DCs accumulate in the uterus; however, their role in pregnancy and, more specifically, implantation, remains unknown. We investigated the function of uterine DCs (uDCs) during implantation using a transgenic mouse model that allows conditional ablation of uDCs in a spatially and temporally regulated manner. Depletion of uDCs resulted in a severe impairment of the implantation process, leading to embryo resorption. Depletion of uDCs also caused embryo resorption in syngeneic and T cell–deficient pregnancies, which argues against a failure to establish immunological tolerance during implantation. Moreover, even in the absence of embryos, experimentally induced deciduae failed to adequately form. Implantation failure was associated with impaired decidual proliferation and differentiation. Dynamic contrast-enhanced MRI revealed perturbed angiogenesis characterized by reduced vascular expansion and attenuated maturation. We suggest therefore that uDCs directly fine-tune decidual angiogenesis by providing two critical factors, sFlt1 and TGF-β1, that promote coordinated blood vessel maturation. Collectively, uDCs appear to govern uterine receptivity, independent of their predicted role in immunological tolerance, by regulating tissue remodeling and angiogenesis. Importantly, our results may aid in understanding the limited implantation success of embryos transferred following in vitro fertilization. PMID:19033665

Stable Water Use Efficiency under Climate Change of Three Sympatric Conifer Species at the Alpine Treeline

PubMed Central

Wieser, Gerhard; Oberhuber, Walter; Gruber, Andreas; Leo, Marco; Matyssek, Rainer; Grams, Thorsten Erhard Edgar

2016-01-01

The ability of treeline associated conifers in the Central Alps to cope with recent climate warming and increasing CO2 concentration is still poorly understood. We determined tree ring stable carbon and oxygen isotope ratios of Pinus cembra, Picea abies, and Larix decidua trees from 1975 to 2010. Stable isotope ratios were compared with leaf level gas exchange measurements carried out in situ between 1979 and 2007. Results indicate that tree ring derived intrinsic water-use efficiency (iWUE) of P. cembra, P. abies and L. decidua remained constant during the last 36 years despite climate warming and rising atmospheric CO2. Temporal patterns in Δ13C and Δ18O mirrored leaf level gas exchange assessments, suggesting parallel increases of CO2-fixation and stomatal conductance of treeline conifer species. As at the study site soil water availability was not a limiting factor iWUE remained largely stable throughout the study period. The stability in iWUE was accompanied by an increase in basal area increment (BAI) suggesting that treeline trees benefit from both recent climate warming and CO2 fertilization. Finally, our results suggest that iWUE may not change species composition at treeline in the Austrian Alps due to similar ecophysiological responses to climatic changes of the three sympatric study species. PMID:27375653

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages

PubMed Central

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-01-01

Objectives l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Methods Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7–13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. Results Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Conclusions Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. PMID:29686031

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

PubMed

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-05-01

l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D 2 -dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T 0 AM and T 1 AM in vitro . Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T 1 AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. © 2018 The authors.

Synergistic induction of apoptosis in primary rat decidual cells by INF-gamma and TNF.

PubMed

Almeida, A; Correia-da-Silva, G; Cepa, M; Bell, S C; Teixeira, N A

2007-03-01

In the rat, in response to blastocyst implantation, stromal cells of the endometrium proliferate and differentiate into decidual cells, forming the decidua. After reaching its maximum development, the decidua undergoes regression. This phenomenon appears to be due to an active process involving apoptosis. As there is sparse knowledge concerning the mechanisms of induction of decidual cell death, the potential role of cytokines present in the uterine environment during pregnancy, such as tumor necrosis factor (TNF) and interferon-gamma (INF-gamma) was explored in primary cultures of rat decidual cells. The effects of these factors upon cellular viability, nuclear morphologic alterations, expression, and enzymatic activities of the effector caspases-3/7 were evaluated. The results obtained demonstrated that in contrast to TNF, which did not induce any alteration, INF-gamma and in association with TNF caused a decrease in cell viability and an increase in the appearance of apoptotic bodies in a time-dependent manner that was augmented in the co-presence of TNF. An increase in caspase-3/7 activities after 12 hr of TNF/INF-gamma treatment was also observed. These findings suggest that INF-gamma expressed in the uterine environment may play an important role in regulating apoptosis through potential synergistic mechanisms with TNF and thereby modulate decidual stability and regression during pregnancy. (c) 2006 Wiley-Liss, Inc.

Environmental versus geographical determinants of genetic structure in two subalpine conifers.

PubMed

Mosca, Elena; González-Martínez, Santiago C; Neale, David B

2014-01-01

Alpine ecosystems are facing rapid human-induced environmental changes, and so more knowledge about tree adaptive potential is needed. This study investigated the relative role of isolation by distance (IBD) versus isolation by adaptation (IBA) in explaining population genetic structure in Abies alba and Larix decidua, based on 231 and 233 single nucleotide polymorphisms (SNPs) sampled across 36 and 22 natural populations, respectively, in the Alps and Apennines. Genetic structure was investigated for both geographical and environmental groups, using analysis of molecular variance (AMOVA). For each species, nine environmental groups were defined using climate variables selected from a multiple factor analysis. Complementary methods were applied to identify outliers based on these groups, and to test for IBD versus IBA. AMOVA showed weak but significant genetic structure for both species, with higher values in L. decidua. Among the potential outliers detected, up to two loci were found for geographical groups and up to seven for environmental groups. A stronger effect of IBD than IBA was found in both species; nevertheless, once spatial effects had been removed, temperature and soil in A. alba, and precipitation in both species, were relevant factors explaining genetic structure. Based on our findings, in the Alpine region, genetic structure seems to be affected by both geographical isolation and environmental gradients, creating opportunities for local adaptation. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Preeclampsia with and without intrauterine growth restriction-Two pathogenetically different entities?

PubMed

Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Stefanovic, Milan; Antic, Vladimir; Djordjevic, Ivana

2016-11-01

The objective of this study is to determine the differences in histopathological features of basal decidua and placenta in cases of preeclampsia with or without fetal intrauterine growth restriction (IUGR). A prospective case-control study included a study group consisting of 30 pregnant women with preeclampsia completed by cesarean section (CS), in 19 of whom preeclampsia was associated with IUGR, and in 11 it was not. The control group consisted of 20 healthy pregnant women delivered by elective CS. Placentas and samples of placental bed obtained during CS were histopathologically (HP) analyzed after hematoxylin-eosin staining and immunohistochemical labeling of Cytokeratin 7 (CK7) trophoblastic cells in decidua. Regarding the HP changes in the spiral arteries in preeclampsia, the most frequent features were inadequate transformation of spiral arteries with poor trophoblastic invasion (70.0%) and fibrinoid necrosis of the media (66.7%), and rarely acute atherosis (33.3%) and thrombosis (30.0%). Villous hypermaturity was more frequently found in placentas of patients with preeclampsia with IUGR (p < 0.05), while there were no differences between subgroups of preeclampsia with and without IUGR regarding some of HP alterations of placental bed. Alterations of the placental bed in terms of decidual vasculopathy are more the characteristics of the preeclampsia itself than IUGR, while changes in placental villi primarily follow the presence of IUGR, which could indicate that preeclampsia with and without IUGR are two pathogenetically different entities.

Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla.

PubMed

Pijnenborg, R; Vercruysse, L; Carter, A M

2011-08-01

In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental bed tissue, showing interstitial and spiral artery invasion of the inner myometrium as well as the decidua. The cell density and depth of trophoblast invasion was equivalent to a human placental bed of 10-14 weeks. Intraluminal trophoblasts were not seen in any of the invaded vessels, allowing no definite conclusions about the origin of the intramural trophoblast and the time-course of spiral artery invasion. A different late second trimester placenta specimen showed scattered extravillous trophoblast in the basal plate and underlying decidua, as well as a remodelled spiral artery containing intramural trophoblast. Absence of inner myometrial tissue precluded assessment of invasion depth in this later specimen. Despite the limited material we can conclude that key aspects of trophoblast invasion are shared by the three hominid species: gorilla, chimpanzee and human. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

PubMed Central

Apps, R.; Sharkey, A.; Gardner, L.; Male, V.; Trotter, M.; Miller, N.; North, R.; Founds, S.; Moffett, A.

2011-01-01

We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray. Villous trophoblast (VT) is in contact with maternal blood and mediates nutrient exchange whereas extravillous trophoblast (EVT) invades the decidua and remodels uterine arteries. Using highly purified first trimester trophoblast we identified over 3000 transcripts that are differentially expressed. Many of these transcripts represent novel functions and pathways that show co-ordinated up-regulation in VT or EVT. In addition we identify new players in established functions such as migration, immune modulation and cytokine or angiogenic factor secretion by EVT. The transition from VT to EVT is also characterised by alterations in transcription factors such as STAT4 and IRF9, which may co-ordinate these changes. Transcripts encoding several members of the immunoglobulin-superfamily, which are normally expressed on leukocytes, were highly transcribed in EVT but not expressed as protein, indicating specific control of translation in EVT. Interactions of trophoblast with decidual leukocytes are involved in regulating EVT invasion. We show that decidual T-cells, macrophages and NK cells express the inhibitory collagen receptor LAIR-1 and that EVT secrete LAIR-2, which can block this interaction. This represents a new mechanism by which EVT can modulate leukocyte function in the decidua. Since LAIR-2 is detectable in the urine of pregnant, but not non-pregnant women, trophoblast-derived LAIR-2 may also have systemic effects during pregnancy. PMID:21075446

Tracing fresh assimilates through Larix decidua exposed to elevated CO₂ and soil warming at the alpine treeline using compound-specific stable isotope analysis.

PubMed

Streit, Kathrin; Rinne, Katja T; Hagedorn, Frank; Dawes, Melissa A; Saurer, Matthias; Hoch, Günter; Werner, Roland A; Buchmann, Nina; Siegwolf, Rolf T W

2013-02-01

How will carbon source-sink relations of 35-yr-old larch trees (Larix decidua) at the alpine treeline respond to changes in atmospheric CO(2) and climate? We evaluated the effects of previously elevated CO(2) concentrations (9 yr, 580 ppm, ended the previous season) and ongoing soil warming (4 yr, + 4°C). Larch branches were pulse labeled (50 at% (13)CO(2)) in July 2010 to trace fresh assimilates through tissues (buds, needles, bark and wood) and non-structural carbon compounds (NCC; starch, lipids, individual sugars) using compound-specific isotope analysis. Nine years of elevated CO(2) did not lead to increased NCC concentrations, nor did soil warming increase NCC transfer velocities. By contrast, we found slower transfer velocities and higher NCC concentrations than reported in the literature for lowland larch. As a result of low dilution with older carbon, sucrose and glucose showed the highest maximum (13)C labels, whereas labels were lower for starch, lipids and pinitol. Label residence times in needles were shorter for sucrose and starch (c. 2 d) than for glucose (c. 6 d). Although our treatments showed no persistent effect on larch carbon relations, low temperature at high altitudes clearly induced a limitation of sink activities (growth, respiration, root exudation), expressed in slower carbon transfer and higher NCC concentrations. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Ovipositional responses of the pulse beetle, Bruchus chinensis (Coleoptera: Bruchidae) to extracts and compounds of Capparis decidua.

PubMed

Upadhyay, Ravi K; Rohatgi, Leena; Chaubey, Mukesh K; Jain, Subhash C

2006-12-27

Extracts of Capparis decidua stems and flowers showed insecticidal and oviposition inhibitory activities against Bruchus chinensis. The LC50 values of these extracts were found to increase with the increase in the polarity of the extract at different exposure periods. For instance, after 96 h, the LC50 values were found to be 3.619, 7.319, and 10.151 microg for CD1, CD2, and CD3, respectively. Extract CD7 was effective only at higher doses. The toxicity was found to be dose- and time-dependent. The females laid lesser number of eggs, when exposed to sublethal doses of different extracts and pure compounds, as compared to control. The maximum oviposition deterrence index was found for extract CD1 followed in decreasing order by CD2, CD3, and CD7. From extract CD1, two compounds were isolated and characterized as triacontanol (C1) and 2-carboxy-1,1-dimethylpyrrolidine (C2). When the females were exposed to sublethal doses of these compounds, they laid lesser number of eggs as compared to the control. C2 was found to have a slightly greater oviposition inhibition effect than C1. From fraction CD7, one novel compound labeled as CDF1 has been isolated and identified as 6-(1-hydroxy-non-3-enyl)tetrahydropyran-2-one. CDF1 has also shown insecticidal and oviposition inhibitory activities against B. chinensis at low concentrations.

Intra-annual dynamics of non-structural carbohydrates in the cambium of mature conifer trees reflects radial growth demands.

PubMed

Simard, Sonia; Giovannelli, Alessio; Treydte, Kerstin; Traversi, Maria Laura; King, Gregory M; Frank, David; Fonti, Patrick

2013-09-01

The presence of soluble carbohydrates in the cambial zone, either from sugars recently produced during photosynthesis or from starch remobilized from storage organs, is necessary for radial tree growth. However, considerable uncertainties on carbohydrate dynamics and the consequences on tree productivity exist. This study aims to better understand the variation in different carbon pools at intra-annual resolution by quantifying how cambial zone sugar and starch concentrations fluctuate over the season and in relation to cambial phenology. A comparison between two physiologically different species growing at the same site, i.e., the evergreen Picea abies Karst. and the deciduous Larix decidua Mill., and between L. decidua from two contrasting elevations, is presented to identify mechanisms of growth limitation. Results indicate that the annual cycle of sugar concentration within the cambial zone is coupled to the process of wood formation. The highest sugar concentration is observed when the number of cells in secondary wall formation and lignification stages is at a maximum, subsequent to most radial growth. Starch disappears in winter, while other freeze-resistant non-structural carbohydrates (NSCs) increase. Slight differences in NSC concentration between species are consistent with the differing climate sensitivity of the evergreen and deciduous species investigated. The general absence of differences between elevations suggests that the cambial activity of trees growing at the treeline was not limited by the availability of carbohydrates at the cambial zone but instead by environmental controls on the growing season duration.

Endogenous lysophosphatidic acid participates in vascularisation and decidualisation at the maternal-fetal interface in the rat.

PubMed

Sordelli, Micaela S; Beltrame, Jimena S; Zotta, Elsa; Gomez, Natalia; Dmytrenko, Ganna; Sales, María Elena; Blois, Sandra M; Davio, Carlos; Martinez, Silvina Perez; Franchi, Ana M; Ribeiro, María L

2017-10-01

Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA 3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA 3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA 3 receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg -1 ) in a total volume of 2μL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA 3 receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA 3 receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.

Comparing growth phenology of co-occurring deciduous and evergreen conifers exposed to drought.

PubMed

Swidrak, Irene; Schuster, Roman; Oberhuber, Walter

2013-12-01

Plant phenological events are influenced by climate factors such as temperature and rainfall. To evaluate phenological responses to water availability in a Spring Heath-Pine wood (Erico-Pinetum typicum), the focus of this study was to determine intra-annual dynamics of apical and lateral growth of co-occurring early successional Larix decidua and Pinus sylvestris and late successional Picea abies exposed to drought. The effect of reduced plant water availability on growth phenology was investigated by conducting a rainfall exclusion experiment. Timing of key phenological dates (onset, maximum rate, end, duration) of growth processes were compared among species at the rain-sheltered and control plot during 2011 and 2012. Shoot and needle elongation were monitored on lateral branches in the canopy at c . 16 m height and radial growth was recorded by automatic dendrometers at c . 1.3 m height of > 120 yr old trees. Different sequences in aboveground growth phenology were detected among the three species under the same growing conditions. While onset of radial growth in April through early May was considerably preceded by onset of needle growth in Larix decidua (5 - 6 weeks) and shoot growth in Pinus sylvestris ( c . 3 weeks), it occurred quite simultaneously with onset of shoot growth in Picea abies . Low water availability had a minor impact on onset of aboveground growth, which is related to utilization of stored water, but caused premature cessation of aboveground growth. At the control plot mean growing season length was 130 days in Pinus sylvestris , 95 days in Larix decidua and 73 days in Picea abies supporting the hypothesis that early successional species are resource expenders, while late successional species are more efficient in utilizing resources and develop safer life strategies. High synchronicity found in culmination of radial growth in late spring (mid-May through early June) prior to occurrence of more favourable environmental conditions in summer might indicate sink competition for carbohydrates to belowground organs. This is supported by completion of apical growth in mid June in all species, except for needle growth of Pinus sylvestris , which lasted until early August. Phenological observations of conifers exposed to drought revealed that tree water status early during the growing season determines total annual aboveground growth and besides temperature, species-specific endogenous and/or environmental factors (most likely photoperiod and/or different threshold temperatures) are involved in controlling apical and lateral growth resumption after winter dormancy.

Comparing growth phenology of co-occurring deciduous and evergreen conifers exposed to drought

PubMed Central

Swidrak, Irene; Schuster, Roman; Oberhuber, Walter

2013-01-01

Plant phenological events are influenced by climate factors such as temperature and rainfall. To evaluate phenological responses to water availability in a Spring Heath-Pine wood (Erico-Pinetum typicum), the focus of this study was to determine intra-annual dynamics of apical and lateral growth of co-occurring early successional Larix decidua and Pinus sylvestris and late successional Picea abies exposed to drought. The effect of reduced plant water availability on growth phenology was investigated by conducting a rainfall exclusion experiment. Timing of key phenological dates (onset, maximum rate, end, duration) of growth processes were compared among species at the rain-sheltered and control plot during 2011 and 2012. Shoot and needle elongation were monitored on lateral branches in the canopy at c. 16 m height and radial growth was recorded by automatic dendrometers at c. 1.3 m height of > 120 yr old trees. Different sequences in aboveground growth phenology were detected among the three species under the same growing conditions. While onset of radial growth in April through early May was considerably preceded by onset of needle growth in Larix decidua (5 - 6 weeks) and shoot growth in Pinus sylvestris (c. 3 weeks), it occurred quite simultaneously with onset of shoot growth in Picea abies. Low water availability had a minor impact on onset of aboveground growth, which is related to utilization of stored water, but caused premature cessation of aboveground growth. At the control plot mean growing season length was 130 days in Pinus sylvestris, 95 days in Larix decidua and 73 days in Picea abies supporting the hypothesis that early successional species are resource expenders, while late successional species are more efficient in utilizing resources and develop safer life strategies. High synchronicity found in culmination of radial growth in late spring (mid-May through early June) prior to occurrence of more favourable environmental conditions in summer might indicate sink competition for carbohydrates to belowground organs. This is supported by completion of apical growth in mid June in all species, except for needle growth of Pinus sylvestris, which lasted until early August. Phenological observations of conifers exposed to drought revealed that tree water status early during the growing season determines total annual aboveground growth and besides temperature, species-specific endogenous and/or environmental factors (most likely photoperiod and/or different threshold temperatures) are involved in controlling apical and lateral growth resumption after winter dormancy. PMID:24273375

Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

PubMed

Leno-Durán, E; Ruiz-Magaña, M J; Muñoz-Fernández, R; Requena, F; Olivares, E G; Ruiz-Ruiz, C

2014-10-10

Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place. This work was supported by the Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (Grant CTS-6183, Proyectos de Investigación de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educación y Ciencia, Spain and the University of Granada. The authors have no conflict of interest. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stress and substance P but not the substance P-metabolite SP5-11 trigger murine abortion by augmenting TNF-alpha levels at the feto-maternal interface.

PubMed

Fest, S; Zenclussen, A C; Joachim, R; Hagen, E; Demuth, H-U; Hoffmann, T

2006-01-01

In a well-established murine abortion model, stress is thought to trigger fetal rejection by inducing a proinflammatory immune response via substance P (SP), being tumour necrosis factor (TNF)-alpha-producing CD8+ T cells involved. Interestingly, the SP metabolite SP5-11 also binds to SP receptors and mediates SP-like effects on immune cells at sites of inflammation. No data were available regarding the effects of SP5-11 on pregnancy outcome in the CBA/J x DBA/2J abortion-prone combination. We investigated the influence of SP5-11 in contrast to stress or SP on the abortion rate and the cytokine production by lymphocytes as well as on the levels of CD8+ T cells. Stress and SP boosted the abortion rate and increased the percentage of type 1 [TNF-alpha, interferon-gamma, interleukin (IL)-12] and type 2 (IL-4 and IL-10) cytokine-producing lymphocytes in blood and decidua, predominantly CD8+ T cells. Interestingly, SP5-11 did not significantly affect the abortion rate or cytokine production in the decidua, while increasing the Th1 and Th2 cytokine production systemically. Our data suggest that stress and SP induce abortion by augmenting the local levels of TNF-alpha, which seems therefore to be a potent trigger of miscarriage. On the contrary, the SP metabolite SP5-11 only affects the systemic cytokine production without boosting the abortion rate in this experimental model.

Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro.

PubMed

Moser, G; Weiss, G; Gauster, M; Sundl, M; Huppertz, B

2015-12-01

How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy? Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space. Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells. As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis. First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5-11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed. The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation. This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations. This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Preculturing effect of thidiazuron on in vitro shoot multiplication and micropropagation round in Capparis decidua (Forsk.) an important multipurpose plant.

PubMed

Bukhari, Najat A W; Siddique, Iram; Perveen, Kahkashan

2016-09-01

An efficient protocol was developed for clonal multiplication of an important shrub: Capparis decidua (Forsk.) Edgew, through in vitro shoot induction and multiplication from nodal explants. Pretreatment of nodal explants in a liquid Murashige and Skoog (MS) medium augmented with various thidiazuron (TDZ) concentrations at relatively high levels (5-100 μM) for different time duration (4, 8, 12 and 16 d), proved a significant approach for in vitro shoot production. After an initial exposure time to TDZ, nodal explants were inoculated onto a MS basal medium devoid of TDZ for further induction and proliferation. The highest regeneration rate (85%), average number of shoots/explant (8.7 ± 0.22) and maximum shoot length (3.9 ± 0.33 cm) were obtained from the nodal explants exposed to 50 μM TDZ for 8 d. The nodal explants excised from the proliferated cultures of TDZ (50 μM) for 8 d were used as explants and showed an enhancement rate after next three round of in vitro propagation. Best results for rooting was obtained by ex vitro treatment of shoots with 200 μM indole-3-butyric acid (IBA) for 20 min. as it produced an average of 5.7 ± 0.41 roots per microshoot with 4.4 ± 0.39 cm root length in 84% shoots. Different planting substrates was tested for maximum survival of hardening off micropropagated plantlets and soilrite proved most effective than others as 97.1 ± 7.21 plantlets survived. All micropropagated plants grew well in natural conditions and showed similar morphology to the mother plant.

Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells

PubMed Central

Li, Min; Piao, Longzhu; Chen, Chie-Pein; Wu, Xianqing; Yeh, Chang-Ching; Masch, Rachel; Chang, Chi-Chang; Huang, S. Joseph

2017-01-01

During human pregnancy, immune tolerance of the fetal semiallograft occurs in the presence of abundant maternal leukocytes. At the implantation site, macrophages comprise approximately 20% of the leukocyte population and act as primary mediators of tissue remodeling. Decidual macrophages display a balance between anti-inflammatory and proinflammatory phenotypes. However, a shift to an M1 subtype is reported in preeclampsia. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are major differentiating factors that mediate M1 and M2 polarization, respectively. Previously, we observed the following: i) the preeclamptic decidua contains an excess of both macrophages and GM-CSF, ii) the preeclampsia-associated proinflammatory cytokines, IL-1β and tumor necrosis factor-α, markedly enhance GM-CSF and M-CSF expression in cultured leukocyte-free first-trimester decidual cells (FTDCs), iii) FTDC-secreted GM-CSF polarizes macrophages toward an M1 subtype. The microenvironment is a key determinant of macrophage phenotype. Thus, we examined proinflammatory stimulation of FTDC-secreted M-CSF and its role in macrophage development. Immunofluorescence staining demonstrated elevated M-CSF–positive decidual cell numbers in preeclamptic decidua. In FTDCs, IL-1β and tumor necrosis factor-α signal through the NF-κB pathway to induce M-CSF production, which does the following: i) enhances differentiation of and elevates CD163 expression in macrophages, ii) increases macrophage phagocytic capacity, and iii) inhibits signal-regulatory protein α expression by macrophages. These findings suggest that FTDC-secreted M-CSF modulates the decidual immune balance by inducing M2 macrophage polarization and phagocytic capacity in response to proinflammatory stimuli. PMID:26970370

Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

PubMed Central

Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

2014-01-01

Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P < 0.05) and formed endothelial-like networks to a greater extent (P < 0.05) than SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P < 0.05), and an increased percentage of dNK cells expressed NKG2D at 10% oxygen (P < 0.05) compared to other oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

A Suppressive Antagonism Evidences Progesterone and Estrogen Receptor Pathway Interaction with Concomitant Regulation of Hand2, Bmp2 and ERK during Early Decidualization

PubMed Central

Mestre-Citrinovitz, Ana C.; Kleff, Veronika; Vallejo, Griselda

2015-01-01

Progesterone receptor and estrogen receptor participate in growth and differentiation of the different rat decidual regions. Steroid hormone receptor antagonists were used to study steroid regulation of decidualization. Here we describe a suppressive interaction between progesterone receptor (onapristone) and estrogen receptor (ICI182780) antagonists and their relation to a rescue phenomenon with concomitant regulation of Hand2, Bmp2 and p-ERK1/2 during the early decidualization steps. Phenotypes of decidua development produced by antagonist treatments were characterized by morphology, proliferation, differentiation, angiogenesis and expression of signaling molecules. We found that suppression of progesterone receptor activity by onapristone treatment resulted in resorption of the implantation sites with concomitant decrease in progesterone and estrogen receptors, PCNA, KI67 antigen, DESMIN, CCND3, CX43, Prl8a2, and signaling players such as transcription factor Hand2, Bmp2 mRNAs and p-ERK1/2. Moreover, FGF-2 and Vegfa increased as a consequence of onapristone treatment. Implantation sites from antagonist of estrogen receptor treated rats developed all decidual regions, but showed an anomalous blood vessel formation at the mesometrial part of the decidua. The deleterious effect of onapristone was partially counteracted by the impairment of estrogen receptor activity with rescue of expression levels of hormone steroid receptors, proliferation and differentiation markers, and the induction of a probably compensatory increase in signaling molecules Hand2, Bmp2 and ERK1/2 activation compared to oil treated controls. This novel drug interaction during decidualization could be applied to pathological endometrial cell proliferation processes to improve therapies using steroid hormone receptor targets. PMID:25897495

Adherent basal plate myometrial fibers in the delivered placenta as a risk factor for development of subsequent placenta accreta.

PubMed

Linn, Rebecca L; Miller, Emily S; Lim, Grace; Ernst, Linda M

2015-12-01

Placenta accreta is implantation of chorionic tissue directly upon the myometrium without normal intervening decidua. The clinical significance of myometrial fibers attached to the basal plate (BPMYO) has yet to be fully elucidated. To determine the importance of depth and quantity of BPMYO in predicting subsequent accreta in the next pregnancy. Women with placentas from two successive pregnancies submitted for pathologic evaluation were included. 50 cases had clinical and/or pathologic diagnosis of accreta in an index pregnancy. 100 controls had no evidence of accreta in an index pregnancy. H&E slides were re-reviewed and stage of accreta/BPMYO was determined. The stages were defined as: Stage 0-no BPMYO; Stage 1-BPMYO with intervening decidua; Stage 2 < 2 decidual cells separating myometrium from chorionic tissue; Stage 3-accreta; Stage 4-increta; Stage 5-percreta. The amount of BPMYO for each placenta was quantified. Prior placentas of cases were twice as likely to have BPMYO compared to controls (84%vs42%, P < 0.001). The frequency of stage 1 BPMYO was not significantly different between the two groups (46%v40%, P = 0.489), but cases were more likely to have higher stages of BPMYO (stage 2-3) in a prior placenta (38%vs2%, P < 0.001). A significantly higher number of BPMYO foci and a larger proportion of BPMYO on the basal plate (6.2%vs0.7%, P < 0.001) in cases compared to controls. Small amounts and low stage BPMYO (stage 1) may be common; however, higher stages of BPMYO (stage 2-3) and greater quantities of BPMYO in a delivered placenta are significantly associated with the subsequent development of accreta. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta

PubMed Central

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-01-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto–maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. PMID:24802103

Tissue-Specific Education of Decidual NK Cells

PubMed Central

Xiong, Shiqiu; Kennedy, Philippa R.; Gardner, Lucy; Farrell, Lydia E.; Chazara, Olympe; Ivarsson, Martin A.; Hiby, Susan E.; Colucci, Francesco; Moffett, Ashley

2015-01-01

During human pregnancy, fetal trophoblast cells invade the decidua and remodel maternal spiral arteries to establish adequate nutrition during gestation. Tissue NK cells in the decidua (dNK) express inhibitory NK receptors (iNKR) that recognize allogeneic HLA-C molecules on trophoblast. Where this results in excessive dNK inhibition, the risk of pre-eclampsia or growth restriction is increased. However, the role of maternal, self–HLA-C in regulating dNK responsiveness is unknown. We investigated how the expression and function of five iNKR in dNK is influenced by maternal HLA-C. In dNK isolated from women who have HLA-C alleles that carry a C2 epitope, there is decreased expression frequency of the cognate receptor, KIR2DL1. In contrast, women with HLA-C alleles bearing a C1 epitope have increased frequency of the corresponding receptor, KIR2DL3. Maternal HLA-C had no significant effect on KIR2DL1 or KIR2DL3 in peripheral blood NK cells (pbNK). This resulted in a very different KIR repertoire for dNK capable of binding C1 or C2 epitopes compared with pbNK. We also show that, although maternal KIR2DL1 binding to C2 epitope educates dNK cells to acquire functional competence, the effects of other iNKR on dNK responsiveness are quite different from those in pbNK. This provides a basis for understanding how dNK responses to allogeneic trophoblast affect the outcome of pregnancy. Our findings suggest that the mechanisms that determine the repertoire of iNKR and the effect of self-MHC on NK education may differ in tissue NK cells compared with pbNK. PMID:26320253

Bisphenol A modulates receptivity and secretory function of human decidual cells: an in vitro study.

PubMed

Mannelli, Chiara; Szóstek, Anna Z; Lukasik, Karolina; Carotenuto, Claudiopietro; Ietta, Francesca; Romagnoli, Roberta; Ferretti, Cristina; Paulesu, Luana; Wołczynski, Slawomir; Skarzynski, Dariusz Jan

2015-08-01

The human endometrium is a fertility-determining tissue and a target of steroid hormones' action. Endocrine disruptors (EDs) can exert adverse effects on the physiological function of the decidua at the maternal-fetal interface. We examined the potential effects of an ED, bisphenol A (BPA), on endometrial maturation/decidualization, receptivity, and secretion of decidual factors (biomarkers). In vitro decidualized, endometrial stromal cells from six hysterectomy specimens were treated with 1  pM-1  μM of BPA, for 24  h and assessed for cell viability and proliferation. Three non-toxic concentrations of BPA (1  μM, 1  nM, and 1  pM) were selected to study its influence on secretion of cell decidualization biomarkers (IGF-binding protein and decidual prolactin (dPRL)), macrophage migration inhibitory factor (MIF) secretion, and hormone receptors' expression (estrogen receptors (ERα and ERβ); progesterone receptors (PRA and PRB); and human chorionic gonadotropin (hCG)/LH receptor (LH-R)). The results showed a decrease in cell viability (P<0.001) in response to BPA at the level of 1  mM. At the non-toxic concentrations used, BPA perturbed the expression of ERα, ERβ, PRA, PRB, and hCG/LH-R (P<0.05). Furthermore, 1  μM of BPA reduced the mRNA transcription of dPRL (P<0.05). Secretion of MIF was stimulated by all BPA treatments, the lowest concentration (1  pM) being the most effective (P<0.001). The multi-targeted disruption of BPA on decidual cells, at concentrations commonly detected in the human population, raises great concern about the possible consequences of exposure to BPA on the function of decidua and thus its potential deleterious effect on pregnancy. © 2015 Society for Reproduction and Fertility.

In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus.

PubMed

Arbab, Ahmed Hassan; Parvez, Mohammad Khalid; Al-Dosari, Mohammed Salem; Al-Rehaily, Adnan Jathlan

2017-07-01

Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC 50 ) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC 50 =10.65), Pulicaria crispa (ethyl acetate extract, IC 50 =14.45), Coccinea grandis (total ethanol extract, IC 50 =31.57), Fumaria parviflora (hexane extract, IC 50 =35.44), Capparis decidua (aqueous extract, IC 50 =66.82), Corallocarpus epigeus (total ethanol extract, IC 50 =71.9), Indigofera caerulea (methanol extract, IC 50 =73.21), Abutilon figarianum (dichloromethane extract, IC 50 =99.76) and Acacia oerfota (total ethanol extract, IC 50 =101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua , C. epigeus, A. figarianum , A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy.

PubMed

Tirado-González, Irene; Freitag, Nancy; Barrientos, Gabriela; Shaikly, Valerie; Nagaeva, Olga; Strand, Magnus; Kjellberg, Lennart; Klapp, Burghard F; Mincheva-Nilsson, Lucia; Cohen, Marie; Blois, Sandra M

2013-01-01

Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

Pregnancy immunology: decidual immune cells.

PubMed

Sanguansermsri, Donruedee; Pongcharoen, Sutatip

2008-01-01

Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro

PubMed Central

Moser, G.; Weiss, G.; Gauster, M.; Sundl, M.; Huppertz, B.

2015-01-01

STUDY QUESTION How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy? SUMMARY ANSWER Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space. WHAT IS KNOWN ALREADY Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells. STUDY DESIGN, SIZE, DURATION As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis. PARTICIPANTS/MATERIALS, SETTING, METHODS First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5–11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed. MAIN RESULTS AND THE ROLE OF CHANCE The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation. LIMITATIONS, REASONS FOR CAUTION This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations. WIDER IMPLICATIONS OF THE FINDINGS This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now. PMID:26493408

Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal stem cells for cancer therapy.

PubMed

Paris, Juan L; de la Torre, Paz; Victoria Cabañas, M; Manzano, Miguel; Grau, Montserrat; Flores, Ana I; Vallet-Regí, María

2017-05-04

A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound.

Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ritvos, O.; Ranta, T.; Jalkanen, J.

1988-05-01

The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purifiedmore » 34 K IGF-BP specifically bound (125I)iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of (125I) iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of (125I) iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with (125I)iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-(3H)aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells.« less

miR-375 induces human decidua basalis-derived stromal cells to become insulin-producing cells.

PubMed

Shaer, Anahita; Azarpira, Negar; Vahdati, Akbar; Karimi, Mohammad Hosein; Shariati, Mehrdad

2014-09-01

This paper focuses on the development of renewable sources of isletreplacement tissue for the treatment of type I diabetes mellitus. Placental tissue-derived mesenchymal stem cells (MSCs) are a promising source for regenerative medicine due to their plasticity and easy availability. They have the potential to differentiate into insulin-producing cells. miR-375 is a micro RNA that is expressed in the pancreas and involved in islet development. Human placental decidua basalis MSCs (PDB-MSCs) were cultured from full-term human placenta. The immunophenotype of the isolated cells was checked for CD90, CD105, CD44, CD133 and CD34 markers. The MSCs (P3) were chemically transfected with hsa-miR-375. Total RNA was extracted 4 and 6 days after transfection. The expressions of insulin, NGN3, GLUT2, PAX4, PAX6, KIR6.2, NKX6.1, PDX1, and glucagon genes were evaluated using real-time qPCR. On day 6, we tested the potency of the clusters in response to the high glucose challenge and assessed the presence of insulin and NGN3 proteins via immunocytochemistry. Flow cytometry analysis confirmed that more than 90% of the cells were positive for CD90, CD105 and CD44 and negative for CD133 and CD34. Morphological changes were followed from day 2. Cell clusters formed during day 6. Insulin-producing clusters showed a deep red color with DTZ. The expression of pancreatic-specific transcription factors increased remarkably during the four days after transfection and significantly increased on day 7. The clusters were positive for insulin and NGN3 proteins, and C-peptide and insulin secretion increased in response to changes in the glucose concentration (2.8 mM and 16.7 mM). In conclusion, the MSCs could be programmed into functional insulin-producing cells by transfection of miR-375.

Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

PubMed

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-09-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. © 2014 British Society for Immunology.

Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

PubMed

Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

2017-09-15

Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by inflammation triggered by monocyte adhesion and increased endothelial cell proliferation. These events are manifest in inflammatory diseases, such as atherosclerosis. Therefore, our results suggest that DBMSCs could be usefully employed as a therapeutic strategy for atherosclerosis.

Placenta‐Derived Decidua Stromal Cells for Treatment of Severe Acute Graft‐Versus‐Host Disease

PubMed Central

Baygan, Arjang; Remberger, Mats; Gustafsson, Britt; Winiarski, Jacek; Khoein, Bita; Moll, Guido; Klingspor, Lena; Westgren, Magnus; Sadeghi, Behnam

2018-01-01

Abstract Severe acute graft‐versus‐host disease (GVHD) is a life‐threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta‐derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM‐MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One‐year survival in the two groups was 47% (95% confidence interval [CI] 23–68) and 76% (95% CI 51–89), respectively (p = .016). For the SR patients, 1‐year survival was 73% (95% CI 37–90) in SR group 2 (n = 11), which was better than 31% (95% CI 11–54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5–42) in BM‐MSC treated (n = 15; p = .0015), and 3% (95% CI 0–14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT‐02172937.) stem cells translational medicine 2018;7:325–332 PMID:29533533

Genetic deletion of Cxcl14 in mice alters uterine NK cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Qichen; Graduate School of the Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan, Beijing 100049; Chen, Hua

2013-06-14

Highlights: •We first examined the expression of Cxcl14 in MLAp and DB of uterus. •We found the uNK cells in MLAp and decidua express Cxcl14. •In Cxcl14{sup −/−} placenta, we found significantly decreased uNK cells. •We first performed microarray to compare the gene expression in MLAp and DB. -- Abstract: The uterine natural killer cells (uNK cells) are the major immune cells in pregnant uterus and the number of uNK cells is dramatically increased during placentation and embryo development. The uNK cells are necessary for the immune tolerance, cytokine secretion and angiogenesis of placenta. Former studies indicated that the populationmore » expansion of uNK cells was accomplished through recruitment of NK cell precursors from the spleen and bone marrow, but not proliferation of NK cells. However, the necessary molecules within this process were little understood. Here in our study, we found the co-localized expression of Cxcl14 protein with uNK cells in E13.5 pregnant uterus. Moreover, we used Cxcl14 knockout mice to examine uNK cells in mesometrial lymphoid aggregate of pregnancy (MLAp) and decidua basalis (DB) of E13.5 pregnant uterus and found significantly decreased uNK cells in Cxcl14{sup −/−} pregnant uteri compared with Cxcl14{sup +/−} pregnant uteri. To further explorer the molecular change in MLAp and DB after Cxcl14 knockout, we isolated the MLAp and DB from Cxcl14{sup +/+} and Cxcl14{sup −/−} pregnant uteri and performed microarray analysis. We found many genes were up and down regulated after Cxcl14 knockout. In conclusion, our results suggested the important function of Cxcl14 in uNK cells and the proper level of Cxcl14 protein were required to recruit NK cells to pregnant uterus.« less

Thermal Properties of Capparis Decidua (ker) Fiber Reinforced Phenol Formaldehyde Composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, G. P.; Mangal, Ravindra; Bhojak, N.

2010-06-29

Simultaneous measurement of effective thermal conductivity ({lambda}), effective thermal diffusivity ({kappa}) and specific heat of Ker fiber reinforced phenol formaldehyde composites have been studied by transient plane source (TPS) technique. The samples of different weight percentage typically (5, 10, 15, 20 and 25%) have been taken. It is found that values of effective thermal conductivity and effective thermal diffusivity of the composites decrease, as compared to pure phenol formaldehyde, as the fraction of fiber loading increases. Experimental data is fitted on Y. Agari model. Values of thermal conductivity of composites are calculated with two models (Rayleigh, Maxwell and Meredith-Tobias model).more » Good agreement between theoretical and experimental result has been found.« less

Galectin signature in normal pregnancy and preeclampsia.

PubMed

Blois, Sandra M; Barrientos, Gabriela

2014-03-01

Members of the galectin family are expressed within the female reproductive tract and have been shown to be involved in multiple biological functions that support the progression of pregnancy. Specific expression patterns of different members of this family have been identified at the maternal decidua and on the placental side. In some cases, mechanisms by which galectins exert their functions have been delineated in adverse pregnancy outcomes. This review summarizes studies on galectins that have been documented to be important for pregnancy maintenance, either supporting the maternal adaptation to pregnancy or the placentation process. In addition, we focus our discussion on the role of galectins in preeclampsia, a specific life-threatening pregnancy disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Nutrient-gene interactions in early pregnancy: a vascular hypothesis.

PubMed

Steegers-Theunissen, R P M; Steegers, E A P

2003-02-10

It is hypothesized that the following periconceptional and early pregnancy nutrient-gene interactions link vascular-related reproductive complications and cardiovascular diseases in adulthood: (1) Maternal and paternal genetically controlled nutrient status affects the quality of gametes and fertilization capacity; (2) The embryonic genetic constitution, derived from both parents, and the maternal genetically controlled nutrient environment determine embryogenesis and fetal growth; (3) Trophoblast invasion of decidua and spiral arteries is driven by genes derived from both parents as well as by maternal nutritional factors; (4) Angiogenesis, vasculogenesis and vascular function are dependent on the genetic constitution of the embryo, derived from both parents, and the maternal genetically controlled nutritional environment.Early intra-uterine programming of vessels may concern the same (in)dependent determinants of vascular-related complications during pregnancy and cardiovascular diseases in later life.

Frost drought in conifers at the alpine timberline: xylem dysfunction and adaptations.

PubMed

Mayr, Stefan; Hacke, Uwe; Schmid, Peter; Schwienbacher, Franziska; Gruber, Andreas

2006-12-01

Drought stress can cause xylem embolism in trees when the water potential (psi) in the xylem falls below specific vulnerability thresholds. At the alpine timberline, frost drought is known to cause excessive winter embolism unless xylem vulnerability or transpiration is sufficiently reduced to avoid critical psi. We compared annual courses of psi and embolism in Picea abies, Pinus cembra, Pinus mugo, Larix decidua, and Juniperus communis growing at the timberline vs. low altitude. In addition, vulnerability properties and related anatomical parameters as well as wood density (D(t)) and wall reinforcement (wall thickness related to conduit diameter) were studied. This allowed an estimate of stress intensities as well as a detection of adaptations that reduce embolism formation. At the alpine timberline, psi was lowest during winter with corresponding embolism rates of up to 100% in three of the conifers studied. Only Pinus cembra and Larix decidua avoided winter embolism due to moderate psi. Minor embolism was observed at low altitude where the water potentials of all species remained within a narrow range throughout the year. Within species, differences in psi50 (psi at 50% loss of conductivity) at high vs. low altitude were less than 1 MPa. In Picea abies and Pinus cembra, psi50 was more negative at the timberline while, in the other conifer species, psi50 was more negative at low altitude. Juniperus communis exhibited the lowest (-6.4 +/- 0.04 MPa; mean +/- SE) and Pinus mugo the highest psi50 (-3.34 +/- 0.03 MPa). In some cases, D(t) and tracheid wall reinforcement were higher than in previously established relationships of these parameters with psi50, possibly because of mechanical demands associated with the specific growing conditions. Conifers growing at the alpine timberline were exposed to higher drought stress intensities than individuals at low altitude. Frost drought during winter caused high embolism rates which were probably amplified by freeze-thaw stress. Although frost drought had a large effect on plant water transport, adaptations in hydraulic safety and related anatomical parameters were observed in only a few of the conifer species studied.

Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

PubMed

Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi

2013-01-01

Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.

Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers

PubMed Central

Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi

2013-01-01

Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection. PMID:24367701

Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion.

PubMed

Qian, Jinfeng; Zhang, Na; Lin, Jing; Wang, Caiyan; Pan, Xinyao; Chen, Lanting; Li, Dajin; Wang, Ling

2018-05-13

The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed. In part II, 35 subjects with URSA and 40 subjects in the early stage of normal pregnancy who chose to undergo an abortion were recruited. Samples of the decidua were collected, and the proportion of immune cells and the expression of related molecules were evaluated. Peripheral regulatory T cells (Treg cells) increased in PCs compared to NPCs, but in women with URSA the flux of Treg cells disappeared when pregnancy occurred. Levels of interleukin-10 (IL-10), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and IL-17 and the ratio of Th17/Treg cells in peripheral blood remained stable among the four groups. At the maternal-fetal interface, the percentage of Treg cells, the level of CTLA-4 of CD4 + CD25 + CD127 lo cells and CD4 + Foxp3 + cells were significantly lower in women with URSA compared to controls, respectively. Levels of transforming growth factor-β1 (TGF-β1) mRNA and protein in the decidua significantly decreased in URSA while levels of IL-6 and tumor necrosis factor-ɑ (TNF-ɑ) and the Th17/Treg ratio significantly increased. In conclusion, peripheral Treg cells did not increase in pregnant women with URSA. The decrease in Treg cells and levels of CTLA-4 and TGF-β1 and as well as the increase in levels of IL-6 and TNF-ɑ, and the Th17/Treg ratio at the maternal-fetal interface might contribute to inappropriate maternal-fetal immune tolerance in URSA.

High-altitude forest sensitivity to global warming: results from long-term and short-term analyses in the eastern italian alps

NASA Astrophysics Data System (ADS)

Carrer, Marco; Anfodillo, Tommaso; Urbinati, Carlo; Carraro, Vinicio

Dendroecological (long-term) analysis and ecophysiological (short-term) monitoring were used interactively to study the responses of tree-ring growth to climate in timberline mixed forests (consisting of Larix decidua Mill., Picea abies (L.) Karst. and Pinus cembra (L.)) in the Italian Eastern Alps (2000-2100 m a.s.l.). Climate-growth linear response functions (LRF) revealed that warm temperatures in June and July have a positive effect on radial growth whereas precipitation during the vegetation period has no effect. Monitoring of the intra-annual radial growth dynamics using band dendrometers confirmed that the radial growth rate of the three species in June and July was greater when air temperatures were higher. Tree-ring formation lasted about 50-60 days (from mid-June to the beginning of August).

Direct seeding woody species for restoration of bottomlands

USGS Publications Warehouse

Twedt, D.J.; Connor, Kristina F

2006-01-01

I direct seeded (broadcast) seeds of 39 species of trees and shrubs using an ATV-mounted rotary spreader to initiate restoration of bottomland forest on retired agricultural sites. Four sites were planted during February, 2000, and 13 additional sites were planted during April and May, 2001. After two growing seasons, stem density of direct-seeded species varied greatly among study plots (range = 0 to 888 stems/ha) but averaged only 110 stems/ha. I recommend that future efforts at direct seeding focus on seven shrub species (Amorpha fruticosa L., Cephalanthus occidentalis L., Cornus spp., Crataegus spp., Ilex decidua Walt., Morus rubra L., and Prunus spp.) and seven tree species (Celtis laevigata Willd., Diospyros virginiana L., Fraxinus spp., Gleditsia triacanthos L., Robinia pseudoacacia L., Taxodium distichum (L.) Rich, and Ulmus spp.) that successfully established in these trials.

Immunological function of vitamin D during human pregnancy.

PubMed

Ji, Jin-Lu; Muyayalo, Kahinho P; Zhang, Yong-Hong; Hu, Xiao-Hui; Liao, Ai-Hua

2017-08-01

The well-established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non-classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal-fetal interface. The insufficiency or deficiency of vitamin D may affect the mother directly and is related to specific pregnancy outcomes, such as preeclampsia, gestational diabetes, and recurrent miscarriage. This article reviews the effects of vitamin D on immune regulation during pregnancy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Adrenomedullin and endocrine control of immune cells during pregnancy.

PubMed

Matson, Brooke C; Caron, Kathleen M

2014-09-01

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

Phytochemical and Biological Activities of Four Wild Medicinal Plants

PubMed Central

Ahmad, Shabir; AbdEl-Salam, Naser M.; Fouad, H.; Rehman, Najeeb Ur; Hussain, Hidayat; Saeed, Wajid

2014-01-01

The fruits of four wild plants, namely, Capparis decidua, Ficus carica, Syzygium cumini, and Ziziphus jujuba, are separately used as traditional dietary and remedial agents in remote areas of Khyber Pakhtunkhwa, Pakistan. The results of our study on these four plants revealed that the examined fruits were a valuable source of nutraceuticals and exhibited good level of antimicrobial activity. The fruits of these four investigated plants are promising source of polyphenols, flavonoids, alkaloids, terpenoids, and saponins. These four plants' fruits are good sources of iron, zinc, copper, manganese, selenium, and chromium. It was also observed that these fruits are potential source of antioxidant agent and the possible reason could be that these samples had good amount of phytochemicals. Hence, the proper propagation, conservation, and chemical investigation are recommended so that these fruits should be incorporated for the eradication of food and health related problems. PMID:25374941

Molecular Regulation of Parturition: The Role of the Decidual Clock.

PubMed

Norwitz, Errol R; Bonney, Elizabeth A; Snegovskikh, Victoria V; Williams, Michelle A; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M

2015-04-27

The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We suggest that it is not a placental clock that regulates the timing of birth, but rather a "decidual clock." Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Molecular Regulation of Parturition: The Role of the Decidual Clock

PubMed Central

Norwitz, Errol R.; Bonney, Elizabeth A.; Snegovskikh, Victoria V.; Williams, Michelle A.; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M.

2015-01-01

The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a “parturition cascade” exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a “placental clock.” We suggest that it is not a placental clock that regulates the timing of birth, but rather a “decidual clock.” Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. PMID:25918180

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.

PubMed

Feng, Liping; Ransom, Carla E; Nazzal, Matthew K; Allen, Terrence K; Li, Yi-Ju; Truong, Tracy; Potts, Lauren C; Seed, Patrick C; Murtha, Amy P

2016-01-01

Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4) and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10-7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.

Dendroclimatic trend and glacial fluctuations in the Central Italian Alps

NASA Astrophysics Data System (ADS)

Pelfini, M.; Santilli, M.; D Agata, C.; Diolaiuti, G.; Smiraglia, C.

2003-04-01

In the Alpine environment, one of the main limiting factors for tree growth is the thermal conditions of the vegetative season. The conifers at high altitude, if not subject to others disturbs, such as geomorphological processes or biological interferences, undergo a development, from which the width of annual rings depends. Five chronologies few centuries long, obtained for the species Larix decidua Mill. and Pinus cembra L. from different valleys of the Central Italian Alps (Alpisella, Valfurva, Gavia and Solda) in proximity of timberline (2000-2550 m of altitude), were analysed and their climatic signal gained; this last one was then related to the recent glacial fluctuations. The chronologies are the averages of many dendrochronological indicized curves obtained from dominant trees with regular growth and extended from 13th-17th century up to the present. The time intervals of the chronologies are the following ones: Pinus cembra: 1752-1999 for Valfurva; 1607-1999 for Gavia; 1593-1999 for Val Solda. With regard to Larix decidua: 1252-1998 for Val Solda; 1784-2001 for Alpisella. The good correspondence between the various chronologies allows to consider them representative of the climatic regional signal. In order to evidence climatic evolution, linear trends based on running mean with period of 11 years have been constructed. Those curves have been compared between them and then overlapped and mediated in order to obtain a climatic signal of regional value that excludes eventual local anomalies. Finally, the growth variations in the chronologies have been compared to known alpine climatic variations and glacial fluctuations. In particular time-distance curves (curves of cumulated frontal variations) of some glaciers from the Ortles-Cevedale Group were utilized. The periods of tree rings growth rate reduction appear well correlated to glacial advancing phases of the Little Ice Age and of the following phases. In particular, growth rate reductions are observable in correspondence of the second decade of the 19th century (main LIA phases) and around 1880, 1920 and 1980, when the glaciers advanced almost all over the Alpine chain. The obtained results agree upon the data from various authors in Europe. This work was conducted as part of 2001 MIUR Project: Glacial retreat in the Italian Alps and the climatic change since deglaciation to the present phase. National Coordinator: Prof. R. Federici, Local Coordinator: Prof. C. Smiraglia

Inactivation of maternal Hif-1α at mid-pregnancy causes placental defects and deficits in oxygen delivery to the fetal organs under hypoxic stress.

PubMed

Kenchegowda, Doreswamy; Natale, Bryony; Lemus, Maria A; Natale, David R; Fisher, Steven A

2017-02-15

A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O 2 ) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function. We used Tamoxifen-inducible Cre-Lox to inactivate Hif-1α in maternal tissues at E8.5 (MATcKO), and used ODD-Luciferase as a reporter of hypoxia in placenta and fetal tissues. MATcKO of Hif-1α reduced the number of uterine natural killer (uNK) cells and Tpbpa-positve trophoblast cells in the maternal decidua at E13.5 -15.5. There were dynamic changes in all three layers of E13.5-15.5 MATcKO placenta. Of note was the under-development of the labyrinth at E15.5 associated with reduced Ki67 and increased TUNEL staining consistent with reduced cell proliferation and increased apoptosis. Labyrinth defects were particularly evident in placentas connected to effectively HIF-1α heterozygous null embryos. MATcKO had no effect on basal ODD-Luciferase activity in fetal organs (heart, liver, brain) at any stage, but at E13.5-15.5 resulted in enhanced induction of the ODD-Luciferase hypoxia reporter when the dam's inspired O 2 was reduced to 8% for 4 hours. MATcKO also slowed the growth after E13.5 of fetuses that were effectively heterozygous for Hif-1α, with most being non-viable at E15.5. The hearts of these E15.5 fetuses were abnormal with reduction in size, thickened epicardium and mesenchymal septum. We conclude that maternal HIF-1α is required for placentation including recruitment of uNK and trophoblast cells into the maternal decidua and other trophoblast cell behaviors. The placental defects render the fetus vulnerable to O 2 deprivation after mid-gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

Critical role of mTOR, PPARγ and PPARδ signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth.

PubMed

Roberti, Sabrina L; Higa, Romina; White, Verónica; Powell, Theresa L; Jansson, Thomas; Jawerbaum, Alicia

2018-06-01

What are the consequences of inhibiting mTOR, the mechanistic target of rapamycin (mTOR), and the peroxisome proliferator activated receptor gamma (PPARγ) and PPARδ pathways in the early post-implantation period on decidual function, embryo viability and feto-placental growth in the rat? mTOR inhibition from Days 7 to 9 of pregnancy in rats caused decidual PPARγ and PPARδ upregulation on Day 9 of pregnancy and resulted in embryo resorption by Day 14 of pregnancy. PPARγ and PPARδ inhibition differentially affected decidual mTOR signaling and levels of target proteins relevant to lipid histotrophic nutrition and led to reduced feto-placental weights on Day 14 of pregnancy. Although mTOR, PPARγ and PPARδ are nutrient sensors important during implantation, the role of these signaling pathways in decidual function and how they interact in the early post-implantation period are unknown. Perilipin 2 (PLIN2) and fatty acid binding protein 4 (FABP4), two adipogenic proteins involved in lipid histotrophic nutrition, are targets of mTOR and PPAR signaling pathways in a variety of tissues. Rapamycin (mTOR inhibitor, 0.75 mg/kg, sc), T0070907 (PPARγ inhibitor, 0.001 mg/kg, sc), GSK0660 (PPARδ inhibitor, 0.1 mg/kg, sc) or vehicle was injected daily to pregnant rats from Days 7 to 9 of pregnancy and the studies were performed on Day 9 of pregnancy (n = 7 per group) or Day 14 of pregnancy (n = 7 per group). On Day 9 of pregnancy, rat decidua were collected and prepared for western blot and immunohistochemical studies. On Day 14 of pregnancy, the resorption rate, number of viable fetuses, crown-rump length and placental and decidual weights were determined. Inhibition of mTOR in the early post-implantation period led to a reduction in FABP4 protein levels, an increase in PLIN2 levels and an upregulation of PPARγ and PPARδ in 9-day-pregnant rat decidua. Most embryos were viable on Day 9 of pregnancy but had resorbed by Day 14 of pregnancy. This denotes a key function of mTOR in the post-implantation period and suggests that activation of PPAR signaling was insufficient to compensate for impaired nutritional/survival signaling induced by mTOR inhibition. Inhibition of PPARγ signaling resulted in decreased decidual PLIN2 and FABP4 protein expression as well as in inhibition of decidual mTOR signaling in Day 9 of pregnancy. This treatment also reduced feto-placental growth on Day 14 of pregnancy, revealing the relevance of PPARγ signaling in sustaining post-implantation growth. Moreover, following inhibition of PPARδ, PLIN2 levels were decreased and mTOR complex 1 and 2 signaling was altered in decidua on Day 9 of pregnancy. On Day 14 of pregnancy, PPARδ inhibition caused reduced feto-placental weight, increased decidual weight and increased resorption rate, suggesting a key role of PPARδ in sustaining post-implantation development. Not applicable. This is an in vivo animal study and the relevance of the results for humans remains to be established. The early post-implantation period is a critical window of development and changes in the intrauterine environment may cause embryo resorption and lead to placental and fetal growth restriction. mTOR, PPARγ and PPARδ signaling are decidual nutrient sensors with extensive cross-talk that regulates adipogenic proteins involved in histotrophic nutrition and important for embryo viability and early placental and fetal development and growth. Funding was provided by the Agencia Nacional de Promoción Científica y Tecnológica de Argentina (PICT 2014-411 and PICT 2015-0130), and by the International Cooperation (Grants CONICET-NIH-2014 and CONICET-NIH-2017) to A.J. and T.J. The authors have no conflicts of interest.

Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro

PubMed Central

Zou, Yanfen; Yu, Xiang; Lu, Jing; Jiang, Ziyan; Zuo, Qing; Fan, Mingsong; Huang, Shiyun

2015-01-01

Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells' metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia. PMID:26357650

Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies.

PubMed

Gamliel, Moriya; Goldman-Wohl, Debra; Isaacson, Batya; Gur, Chamutal; Stein, Natan; Yamin, Rachel; Berger, Michael; Grunewald, Myriam; Keshet, Eli; Rais, Yoach; Bornstein, Chamutal; David, Eyal; Jelinski, Adam; Eisenberg, Iris; Greenfield, Caryn; Ben-David, Arbel; Imbar, Tal; Gilad, Ronit; Haimov-Kochman, Ronit; Mankuta, David; Elami-Suzin, Matan; Amit, Ido; Hanna, Jacob H; Yagel, Simcha; Mandelboim, Ofer

2018-05-15

Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-γ and VEGFα, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation. Copyright © 2018 Elsevier Inc. All rights reserved.

Fetal loss in homozygous mutant Norrie disease mice: a new role of Norrin in reproduction.

PubMed

Luhmann, Ulrich F O; Meunier, Dominique; Shi, Wei; Lüttges, Angela; Pfarrer, Christiane; Fundele, Reinald; Berger, Wolfgang

2005-08-01

Mutations in the Norrie disease pseudoglioma gene (NDP) are known to cause X-linked recessive Norrie disease. In addition, NDP mutations have been found in other vasoproliferative retinopathies such as familial exudative vitreoretinopathy, retinopathy of prematurity, and Coats disease, suggesting a role for Norrin in vascular development. Here we report that female mice homozygous for the Norrie disease pseudoglioma homolog (Ndph) knockout allele exhibit almost complete infertility, while heterozygous females and hemizygous males are fertile. Histological examinations and RNA in situ hybridization analyses revealed defects in vascular development and decidualization in pregnant Ndph-/- females from embryonic day 7 (E7) onwards, resulting in embryonic loss. Using RT-PCR analyses we also demonstrate, for the first time, the expression of Ndph in mouse uteri and deciduae as well as the expression of NDP in human placenta. Taken together, these data provide strong evidence for Norrin playing an important role in female reproductive tissues. Copyright 2005 Wiley-Liss, Inc

A bioinformatics transcriptome meta-analysis highlights the importance of trophoblast differentiation in the pathology of hydatidiform moles.

PubMed

Desterke, Christophe; Slim, Rima; Candelier, Jean-Jacques

2018-05-01

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal trophoblastic development, migration/invasion of the extravillous trophoblast in the decidua. These abnormalities are established in a hypoxic environment during the first trimester of gestation. Using text mining, we identified 72 unique genes that are linked to HM (HM-linked genes) that we studied by bioinformatic analysis in publicly available transcriptomes of primary chorionic villous cells (cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, and arterial and venous endothelial) isolated from normal placentas or established trophoblastic cell lines cultured under different oxygen concentrations. We show that the majority of HM-linked genes (75%) are involved in normal trophoblastic differentiation, arranged in clusters, and some of them are implicated in chorionic villous invasion or regulated by oxygen concentrations. Our analysis integrates the various aspects of the pathophysiology of HM and highlights the importance of trophoblastic differentiation in this pathology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

PubMed

Turco, Margherita Y; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G E; Brosens, Jan J; Critchley, Hilary O; Simons, Benjamin D; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J

2017-05-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically-defined medium

PubMed Central

Turco, Margherita Y.; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J.; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G.E.; Brosens, Jan J.; Critchley, Hilary O.; Simons, Benjamin D.; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J.

2017-01-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem cell-derived organoid cultures to generate 3D cultures of normal and decidualised human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation. PMID:28394884

Characterization of tumor infiltrating Natural Killer cell subset

PubMed Central

Nissan, Aviram; Darash-Yahana, Merav; Peretz, Tamar; Mandelboim, Ofer; Rachmilewitz, Jacob

2015-01-01

The presence of tumor-infiltrating Natural Killer (NK) within a tumor bed may be indicative of an ongoing immune response toward the tumor. However, many studies have shown that an intense NK infiltration, is associated with advanced disease and may even facilitate cancer development. The exact role of the tumor infiltrating NK cells and the correlation between their presence and poor prognosis remains unclear. Interestingly, during pregnancy high numbers of a specific NK subset, CD56brightCD16dim, are accumulated within first trimester deciduas. These decidual NK (dNK) cells are unique in their gene expression pattern secret angiogenic factors that induce vascular growth. In the present study we demonstrate a significant enrichment of a CD56brighCD16dim NK cells within tumors. These NK cells express several dNK markers including VEGF. Hence, this study adds new insights into the identity of tumor residual NK cells, which has clear implications for the treatment of human cancer. PMID:26079948

Development of the inverted visceral yolk sac in three species of caviids (Rodentia, Caviomorpha, Caviidae).

PubMed

Miglino, M A; Franciolli, A L R; de Oliveira, M F; Ambrósio, C E; Bonatelli, M; Machado, M R F; Mess, A

2008-08-01

Guinea pig related rodents possess numerous derived placental characters. We attempt to identify diversity within the visceral yolk sac and its association with the chorioallantoic placenta in three species of caviids, two of them possessing a capsule formed by the decidua that covers the chorioallantoic placenta. The results verify that in early pregnancy all three species have an inverted yolk sac placenta. In advanced pregnancy the species differ: Galea spixii, as representative without a capsule, bear a yolk sac in apposition to the chorioallantoic placenta with signs of exchange activity until term. Galea is similar to other caviomorphs in this respect. In Dasyprocta leporina and Cuniculus paca, the representatives possessing a capsule, the yolk sac endoderm lacks signs of substance exchange. Evidently, the presence of a capsule prevents such an interaction. The variations established here must be considered if animal models for human placentation are required which have restricted access to the chorioallantoic placenta from the outside.

Influence of age and composition of shelterbelts plants on enzyme activity and auxine - phytophormone IAA concentrations in soils

NASA Astrophysics Data System (ADS)

Wojciech Szajdak, Lech; Gaca, Wioletta; Meysner, Teresa; Styła, Katarzyna; Maryganova, Victoria

2010-05-01

The investigations were carried out in Dezydery Chlapowski Agroecological Landscape Park in Turew (40 km South-West of Poznań, West Polish Lowlands, 16° 45 E and 52° 01 N). The soil samples were taken from two shelterbelts differing the age and the composition of trees. First 200-years-old shelterbelt is consisting mainly by Robinia pseudacacia and small admixture of Quercus robur and Larix deciduas. It has 2 kilometers of length and 36 meters of width. The second one new shelterbelt (many species) was created in 1993 and consists of several species of plants such as: Quercus pertraea and Quercus robur, Larix decidua, Pinus silvestris, Sorbus aucuparia, Sorbus intermedia and Tilia cordata. Its length is 340 meters and its width is 17.5 meters. All shelterbelts and adjoining cultivated fields were introduced on Hapludalfs soils (according to FAO classification). In soil under two shelterbelts and adjoining cultivated fields the activity of the following enzymes nitrate reductase, urease, xanthine oxidase, phenol oxidase, peroxidase activity were measured. In addition, the concentrations of iron ions, indole-3-acetic acids, total organic carbon, dissolved organic carbon, total nitrogen, ammonium and nitrates were determined. In soils under shelterbelts compared to adjoining cultivated fields higher content of organic matter was observed, because the accumulation of soil organic matter under shelterbelts is suggested to be the main mechanism of long-term withdrawal of various chemical elements from cycling in the agroecosystems. However, many chemical, biochemical, physical and biological processes control conversions of organic compounds in soils and finally these processes depend on the organic matter content and particularly on humic substances. Due to a very good developed root system of trees in shelterbelts than cultivated plants, they transpire more than 34% water than cultivated fields and intensively take up nutrients and finally improve quality of ground and surface water. The acidity of the soil under the 200-years-old shelterbelt was the highest and during the entire vegetation season pH ranged from 3.19 to 3.51, while for the soil of adjoining cultivated field pH values were much higher (5.03-5.65). However, there are not much differences between pH of the soil under young shelterbelt (created in 1993) and the soil of adjoining cultivated field (3.73-5.25 and 3.72-4.15, respectively). The activities of enzymes and all chemical compounds were the highest in soil under 200-years-old shelterbelt than in soil under young shelterbelt and two adjoining cultivated fields to both shelterbelts.

Time since death and decay rate constants of Norway spruce and European larch deadwood in subalpine forests determined using dendrochronology and radiocarbon dating

NASA Astrophysics Data System (ADS)

Petrillo, Marta; Cherubini, Paolo; Fravolini, Giulia; Marchetti, Marco; Ascher-Jenull, Judith; Schärer, Michael; Synal, Hans-Arno; Bertoldi, Daniela; Camin, Federica; Larcher, Roberto; Egli, Markus

2016-03-01

Due to the large size (e.g. sections of tree trunks) and highly heterogeneous spatial distribution of deadwood, the timescales involved in the coarse woody debris (CWD) decay of Picea abies (L.) Karst. and Larix decidua Mill. in Alpine forests are largely unknown. We investigated the CWD decay dynamics in an Alpine valley in Italy using the chronosequence approach and the five-decay class system that is based on a macromorphological assessment. For the decay classes 1-3, most of the dendrochronological samples were cross-dated to assess the time that had elapsed since tree death, but for decay classes 4 and 5 (poorly preserved tree rings) radiocarbon dating was used. In addition, density, cellulose, and lignin data were measured for the dated CWD. The decay rate constants for spruce and larch were estimated on the basis of the density loss using a single negative exponential model, a regression approach, and the stage-based matrix model. In the decay classes 1-3, the ages of the CWD were similar and varied between 1 and 54 years for spruce and 3 and 40 years for larch, with no significant differences between the classes; classes 1-3 are therefore not indicative of deadwood age. This seems to be due to a time lag between the death of a standing tree and its contact with the soil. We found distinct tree-species-specific differences in decay classes 4 and 5, with larch CWD reaching an average age of 210 years in class 5 and spruce only 77 years. The mean CWD rate constants were estimated to be in the range 0.018 to 0.022 y-1 for spruce and to about 0.012 y-1 for larch. Snapshot sampling (chronosequences) may overestimate the age and mean residence time of CWD. No sampling bias was, however, detectable using the stage-based matrix model. Cellulose and lignin time trends could be derived on the basis of the ages of the CWD. The half-lives for cellulose were 21 years for spruce and 50 years for larch. The half-life of lignin is considerably higher and may be more than 100 years in larch CWD. Consequently, the decay of Picea abies and Larix decidua is very low. Several uncertainties, however, remain: 14C dating of CWD from decay classes 4 and 5 and having a pre-bomb age is often difficult (large age range due to methodological constraints) and fall rates of both European larch and Norway spruce are missing.

Topical Treatment of Dermatophytic Lesion on Mice (Mus musculus) Model.

PubMed

Sharma, Bindu; Kumar, Padma; Joshi, Suresh Chandra

2011-06-01

Antidermatophytic potential of three weed plants viz. Tridax procumbens L., Capparis decidua (forsk) Edgew and Lantana camara L. were explored and experimentally induced dermatophytic lesion was topically treated in mice. Microbroth dilution method was carried out for determination of MIC and MFC of different extracts of selected plants. In animal studies, mice were experimentally inoculated with Trichophyton mentagrophytes and infected animals were topically treated with 5 mg/g terbinafine and two concentrations, i.e., 5 and 10 mg/g of test extract ointment. Complete recovery from the infection was observed on 12th day of treatment for reference drug terbinafine (5 mg/g) and 10 mg/g concentration of test extract ointment whereas 5 mg/g concentration of test extract ointment showed complete cure on 16th day of treatment. Fungal burden was also calculated by culturing skin scrapings from infected animals of different groups. Test extract ointment successfully treated induced dermatophytosis in mice without any disease recurrence incidences, thereby indicating efficacy of test extract as an excellent topical antifungal agent for the cure of dermatophytosis.

Tim-3 and PD-1 regulate CD8+ T cell function to maintain early pregnancy in mice

PubMed Central

XU, Yuan-Yuan; WANG, Song-Cun; LIN, Yi-Kong; LI, Da-Jin; DU, Mei-Rong

2017-01-01

During pregnancy, CD8+ T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8+ T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3+PD-1+CD8+ T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy. Furthermore, normal pregnant CBA/J females challenged with Tim-3- and/or PD-1-blocking antibodies were more susceptible to fetal resorption. These findings indicate that Tim-3 and PD-1 pathways play critical roles in regulating CD8+ T cell function and maintaining normal pregnancy. PMID:28331165

INTRAUTERINE FATE OF INVASIVE TROPHOBLAST CELLS1

PubMed Central

Rosario, Gracy X.; Ain, Rupasri; Konno, Toshihiro; Soares, Michael J.

2009-01-01

Invasion of trophoblast cells into the uterine spiral arteries and the uterine wall is characteristic of hemochorial placentation. In the rat, trophoblast cells penetrate through the uterine decidua and well into the metrial gland. In this report, we examined the fate of these invasive trophoblast cells following parturition. Invasive trophoblast endocrine cells were retained in the postpartum mesometrial uterus in the rat. The demise of invasive trophoblast cells was followed by the appearance of differentiated smooth muscle cells surrounding blood vessels previously lined by invasive trophoblast cells and an infiltration of macrophages. Regulation of intrauterine trophoblast cell fate was investigated following premature removal of the fetus or removal of the fetus and chorioallantoic placenta. The presence of the fetus affected the distribution of invasive trophoblast cells within the uterus but did not negatively impact their survival. Premature removal of all chorioallantoic placentas and associated fetuses from a uterus resulted in extensive removal of intrauterine trophoblast cells. In summary, the postpartum demise of intrauterine invasive trophoblast cells is a dynamic developmental event regulated in part by the removal of trophic signals emanating from the chorioallantoic placenta. PMID:19344949

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

PubMed Central

Simmons, Heather A.; Salamat, M. Shahriar; Thoong, Troy H.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Vosler, Logan J.; Mohns, Mariel S.; Breitbach, Meghan E.; Stewart, Laurel M.; Newman, Christina M.; Graham, Michael E.; Turski, Patrick A.; Post, Jennifer; Hayes, Jennifer M.; Schotzko, Michele L.; Permar, Sallie R.; Rakasz, Eva G.; Capuano, Saverio; Tarantal, Alice F.; Osorio, Jorge E.; O’Connor, Shelby L.

2017-01-01

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated. PMID:28542585

Association of increased S100A8 serum protein with early pregnancy loss.

PubMed

Nair, Rohini R; Khanna, Anuradha; Singh, Kiran

2015-02-01

The contribution of systemic S100A8 protein in menstrual cycle, pregnancy, and early pregnancy loss (EPL) is not known. Altered expression of S100A8 in maternal decidua is associated with recurrent early pregnancy loss. The objective of this study was to investigate the systemic level of S100A8 in different phases of menstrual cycle, different trimester of pregnancy, and in EPL. Level of S100A8 was investigated in serum samples of the subjects through enzyme-linked immunosorbent assay (ELISA). S100A8 levels were elevated during proliferative phase of menstrual cycle. We found no statistical difference in S100A8 level in different trimester of pregnancy. S100A8 level was found to be significantly elevated in patients with EPL. This is the first study evaluating the systemic level of S100A8 predicting its role during menstrual cycle and pregnancy. It opens a new perspective in which S100A8 can be used as a prognostic marker for EPL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intrauterine air impairs embryonic postimplantation development in mice.

PubMed

Liu, Ruonan; Li, Yimeng; Miao, Yanping; Wei, Yanhui; Guan, Mo; Zhou, Rongyan; Li, Xiangyun

2017-12-01

Although most embryologists load air bubbles into the catheter along with embryos during embryo transfer, the effects of these air bubbles on embryo transfer success rate are not clear. Air bubbles were nonsurgically injected into unilateral uterine horns of mice to demonstrate the negative effects of intrauterine air bubbles on embryonic development. Our data showed that when air bubbles are nonsurgically injected into unilateral uterine horns of pregnant 4days mice the litter size is significantly decreased. Four days after the introduction of air, abnormal decidua and dead conceptuses were detected in the uterine horns receiving the air bubbles. In addition, intrauterine air also significantly impaired murine embryo transfer success rates, and induced an increase in endometrial capillary permeability and decidualization in mice on day 4 of pseudopregnancy. These results strongly indicated that the air bubbles loaded into embryo transfer catheters to bracket the embryo-containing medium may have negative effect on embryonic implantation and development. Intrauterine air impaired murine embryonic postimplantation development, and this provided some clues for improving embryo transfer techniques in human. Copyright © 2017 Elsevier B.V. All rights reserved.

Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population.

PubMed

da Silva, Ronaldo Celerino; Segat, Ludovica; Zanin, Valentina; Arraes, Luiz Claudio; Crovella, Sergio

2012-11-01

DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Lessons from reproductive immunology for other fields of immunology and clinical approaches.

PubMed

Markert, Udo R; Fitzgerald, Justine S; Seyfarth, Lydia; Heinzelmann, Joana; Varosi, Frauke; Voigt, Sandra; Schleussner, Ekkehard; Seewald, Hans-Joachim

2005-01-01

Reproduction is indispensable to evolution and, thus, life. Nonetheless, it overcomes common rules known to established life. Immunology of reproduction, and especially the tolerance of two genetically distinct organisms and their fruitful symbiosis, is one of the most imposing paradox of life. Mechanisms, which are physiologically used for induction of said tolerance, are frequently abused by pathogens or tumors intending to escape the host's immune response. Understanding the regulation of immune responses in pregnancy and the invasion of allogeneic fetus-derived trophoblast cells into the decidua may lead to new therapeutic concepts. In transplantation, knowledge concerning local physiological immunotolerance may be useful for the development of new therapies, which do not require a general immune suppression of the patient. In immunological disorders, such as autoimmune diseases or allergies, immune deviations occur which are either prevented during pregnancy or have parallels to pregnancy. Vice versa, lessons from other fields of immunology may also offer new notions for the comprehension of reproductive immunology and may lead to new therapies for the treatment of pregnancy-related problems.

ENZYME DISTRIBUTION IN THE RAT FETUS AND PLACENTA FOLLOWING THE ADMINSTRATION OF ETHIONINE

PubMed Central

Schultz, Richard L.; Schultz, Phyllis W.

1962-01-01

Enzyme changes which accompany ethionine-induced resorption of the rat conceptus have been studied by both histochemical and biochemical techniques. Pregnant rats were injected with ethionine over a 3-day period prior to autopsy on day 12 of pregnancy. Sections of the whole conceptus were studied for acid phosphatase with both the Burstone and Gomori methods and for succinoxidase activity with nitro-BT. Biochemical determinations of cathepsins, acid phosphatase, and succinoxidase were performed on homogenates of the fetuses, placentae, and deciduas basalis from ethionine-treated and saline-treated rats. The histochemical study has shown that resorption is accompanied by an increase in the size and number of acid phosphatase granules in the decidual tissues and a concurrent loss of acid phosphatase granules in the fetal tissues. Biochemical methodology indicated that there was no increase in total cathepsin or acid phosphatase activities in the resorbing tissues. No change in succinoxidase activity was found with either histochemical or biochemical techniques. The significance of these results was discussed with reference to the lysosome hypothesis. PMID:13987236

Uterine NK Cells Are Critical in Shaping DC Immunogenic Functions Compatible with Pregnancy Progression

PubMed Central

Freitag, Nancy; Otto, Teresa; Thijssen, Victor L. J. L.; Moschansky, Petra; von Kwiatkowski, Petra; Klapp, Burghard F.; Winterhager, Elke; Bauersachs, Stefan; Blois, Sandra M.

2012-01-01

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression. PMID:23056436

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

PubMed

Tirado-González, Irene; González, Irene Tirado; Barrientos, Gabriela; Freitag, Nancy; Otto, Teresa; Thijssen, Victor L J L; Moschansky, Petra; von Kwiatkowski, Petra; Klapp, Burghard F; Winterhager, Elke; Bauersachs, Stefan; Blois, Sandra M

2012-01-01

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.

Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

PubMed

Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

2017-02-15

Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission. Copyright © 2017 American Society for Microbiology.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

[Physiological significance of IGF-I and its binding proteins on fetal growth and maturation].

PubMed

Iwashita, M

1994-08-01

Insulin-like growth factor-I (IGF-I) is one of growth factors that circulates bound to specific, high affinity binding proteins (IGFBPs). Physiological significance of IGF-I and IGFBPs on fetal growth is investigated in this study. In mother, circulating levels of IGF-I are increased during pregnancy in which placental hormones take the place of pituitary GH to regulate IGF-I during pregnancy and correlates with fetal birth weight. IGFBPs except IGFBP-1 in the maternal circulation are markedly reduced compared to those of non pregnant women due to increased activity of protease(s) while IGFBP-1 gradually increased throughout pregnancy and negatively correlates with fetal weight. IGF-I stimulated 3H-AIB uptake and release by cultured trophoblast cells in a dose dependent manner. Furthermore, fetal growth and the transfer of 3H-AIB to fetus is inhibited when IGF-I is neutralized by polyclonal antibody. These results indicate that maternal IGF-I stimulates fetal growth by activating placental transport of nutrients to fetus. In contrast, IGFBP-1 inhibits both 125I-IGF-I binding to placental membrane and 3H-glycine uptake of trophoblast cells by IGF-I in a dose dependent manner. Moreover, fetal growth and the transfer of 3H-AIB to fetus are accelerated when IGFBP-1 is neutralized by polyclonal antibody, suggesting that maternal IGFBP-1 inhibits fetal growth by inhibiting IGF-I action on the placenta. IGF-I and four IGFBPs including IGFBP-1, -2, -3, and -4 are localized in cytotrophoblast of term placenta. Similarly IGFBP-1, -2, and -4 are detected in medium conditioned by term decidua cells by Western ligand blot in which release of IGFBP-1 and -4 are diminished by IGF-I and all three IGFBPs are increased by progesterone. Thus, there is a complicated autocrine/paracrine regulation between decidua and placenta and IGF-I action on fetal growth is presumed to be modified by this local regulation. Fetal levels of IGF-I and IGFBP-1 are positively and negatively correlate with fetal weight, respectively. The isomers of phosphorylated IGFBP-1 in cord sera are separated by anion ion exchange chromatography in which one nonphosphorylated and four phosphorylated IGFBP-1 are detected. In pared blood samples from mid-term delivery, percentage of nonphosphorylated IGFBP-1 is higher in fetal blood compared to those in mother. Similarly, percentage of nonphosphorylated IGFBP-1 is elevated in AFD infants than is SFD infants from term delivery. Thus, the proportion of nonphosphorylated and phosphorylated isomers of IGFBP-1 varies corresponding to fetal growth.(ABSTRACT TRUNCATED AT 400 WORDS)

A stochastic model for early placental development†

PubMed Central

Cotter, Simon L.; Klika, Václav; Kimpton, Laura; Collins, Sally; Heazell, Alexander E. P.

2014-01-01

In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions. PMID:24850904

Effects of atmospheric and climate change at the timberline of the Central European Alps

PubMed Central

Wieser, Gerhard; Matyssek, Rainer; Luzian, Roland; Zwerger, Peter; Pindur, Peter; Oberhuber, Walter; Gruber, Andreas

2011-01-01

This review considers potential effects of atmospheric change and climate warming within the timberline ecotone of the Central European Alps. After focusing on the impacts of ozone (O3) and rising atmospheric CO2 concentration, effects of climate warming on the carbon and water balance of timberline trees and forests will be outlined towards conclusions about changes in tree growth and treeline dynamics. Presently, ambient ground-level O3 concentrations do not exert crucial stress on adult conifers at the timberline of the Central European Alps. In response to elevated atmospheric CO2 Larix decidua showed growth increase, whereas no such response was found in Pinus uncinata. Overall climate warming appears as the factor responsible for the observed growth stimulation of timberline trees. Increased seedling re-establishment in the Central European Alps however, resulted from invasion into potential habitats rather than upward migration due to climate change, although seedlings will only reach tree size upon successful coupling with the atmosphere and thus loosing the beneficial microclimate of low stature vegetation. In conclusion, future climate extremes are more likely than the gradual temperature increase to control treeline dynamics in the Central European Alps. PMID:21379395

The role of inflammation in preterm birth--focus on periodontitis.

PubMed

Klebanoff, M; Searle, K

2006-12-01

It is universally accepted that acute inflammation is responsible for a substantial fraction of preterm births, particularly early cases. Much of this inflammation is caused by intrauterine infection. There is also evidence that infection and perhaps inflammation remote from the genitourinary tract can trigger preterm labour. Several studies have suggested that periodontitis during pregnancy increases the risk of preterm birth. Periodontitis may cause preterm birth by causing low-grade bacteraemia, which lodges in the decidua, chorion and amnion or by releasing endotoxin into the maternal circulation, which triggers intrauterine inflammation and preterm birth. Alternatively, it may release cytokines and other inflammatory products, which then trigger preterm labour. It is also conceivable that periodontitis might serve as a marker for other unhealthy behaviours, or immune hyperresponsiveness and that hyperresponsiveness to low-grade intrauterine infection itself might cause preterm birth. Currently, there are few data available to distinguish these possibilities. Such distinctions are important since they have clear implications for whether treatment of periodontitis might reduce the incidence of preterm birth. Several clinical trials of treatment of periodontitis are continuing, but until their results are known there is currently little evidence that treatment of periodontitis during pregnancy reduces the incidence of preterm birth.

The up side of decidual natural killer cells: new developments in immunology of pregnancy.

PubMed

Jabrane-Ferrat, Nabila; Siewiera, Johan

2014-04-01

Early phases of human pregnancy are associated with the accumulation of a unique subset of natural killer (NK) cells in the maternal decidua. Decidual NK (dNK) cells that are devoid of cytotoxicity play a pivotal role in successful pregnancy. By secreting large amounts of cytokines/chemokines and angiogenic factors, dNK cells participate in all steps of placentation including trophoblast invasion into the maternal endometrium and vascular remodelling. In this review, we summarize some of dNK cell features and discuss more recent exciting data that challenge the conventional view of these cells. Our new data demonstrate that dNK cells undergo fine tuning or even subvert their classical inhibitory machinery and turn into a real defence force in order to prevent the spread of viruses to fetal tissue. Today it is not clear how these phenotypic and functional adaptations impact cellular cross-talk at the fetal-maternal interface and tissue homeostasis. Ultimately, precise understanding of the molecular mechanisms that govern dNK cell plasticity during congenital human cytomegalovirus infection should lead to the design of more robust strategies to reverse immune escape during viral infection and cancer. © 2013 John Wiley & Sons Ltd.

New, rare or remarkable microfungi in the Italian Alps (Carnic Alps)--part I--ascomycotina.

PubMed

Feige, G B; Ale-Agha, N; Jensen, M; Christiaans, B; Kricke, R

2004-01-01

During our observations in the SE part of the Carnic Alps in the year 2003 we were able to collect and identify 35 ascomycetes on trees and dead wood. Among these one can find numerous ascomycetes of different orders e.g. Pyrenomycetes, Loculoascomycetes and Discomycetes. Some species like Botryosphaeria ribis GROSENLUCHER & DUGGAR on Ribes alpinum L., Dothiora pyrenophora (FR.) FR. on Sorbus aucuparia L., Gemmamyces piceae (BORTH.) CASAGO. on Picea excelsa (LAM.) LINK, Glomerella montana (SACC.) v. ARX & E. MULLER on Sesleria caerulea (L.) ARD, Hymenoscyphus immutabilis (Fuck.) Dennis on Alnus incana (L.) Moench, Hysterographium fraxini (PERS. Ex. FR.) de Not. on Fraxinus ornus L., Lachnellula willkommii (Hartig) DENNIS [= Trichascyphella willkommii (Hartig) NANNF.] on Larix decidua MILL.,Leptosphaeria lycopodina (Mont.) SACC. on Lycopodium annotinum L., Mollisia adenostylidis REHM. on Adenostyles glabra (MILL.) DC., Pezicula cinnamomea (DC.)SACC. [ana: Cryptosporiopsis quercina PETRAK] on Quercus robur L., Pyrenopeziza petiolaris (A. & S. Ex FR.) NANNF. on Acer pseudoplatanus L., Tapesia rosae (PERS.) FUCKEL on Rosa canina L., are new for this area. All specimen are deposited in the Herbarium ESS Mycotheca Parva, Collection G.B. Feige/N. Ale-Agha.

Placental Apoptosis in Health and Disease

PubMed Central

Sharp, Andrew N.; Heazell, Alexander E.P.; Crocker, Ian P.; Mor, Gil

2011-01-01

Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre-eclampsia, and intra-uterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell-types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental-derived material is thought to provoke the endothelial dysfunction of pre-eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets. PMID:20367628

Localization and counting of CD68-labelled macrophages in placentas of normal and preeclamptic women

NASA Astrophysics Data System (ADS)

Al-khafaji, Lina Ali; Al-Yawer, Malak A.

2017-09-01

In the human placenta, there are two types of placental macrophages Hofbauer cells of fetal villi and decidual macrophages of maternal decidua basalis. Placental macrophages adopt a specialized phenotype that may hold a key role in synthesis of vital mediators involved in the establishment and maintenance of pregnancy, parturition and maternal-fetal tolerance. Aberrant behavior of these macrophages can affect trophoblast functions and placental development and potentially can lead to a spectrum of adverse pregnancy outcomes. Yet, the populations and functions of placental macrophages in women with different parity and women with preeclampsia remain ill-defined and subject of controversy. Immuno-histochemical study using CD68 primary antibody revealed a significant increase in number of CD68 positive fetal and decidual macrophages in preeclamptic subgroups as compared to controls. Fetal macrophages were seen to be localized near fetal vessel wall and near syncytium which were significantly increased in primiparous preeclamptic subgroup. Our study assumed that there may be intermingling of signals between macrophages and trophoblast cells resulting in impairment of trophoblast invasion and spiral artery remodeling which is the primary placental defect in pregnancies complicated by preeclampsia.

[IDENTIFICATION OF CAUSES OF EARLY PREGNANCY LOSSES ACCORDING TO HYSTOMORPHOLOGIC FEATURES].

PubMed

Gotsiridze, K; Kintraia, N; Pailodze, M; Gogia, T; Tsaava, F

2017-01-01

Retrospective analysis of the early spontaneous abortions has been conducted (486 cases). Histomorphologic analysis of the curettage material contents erveledinvolutive-regressive developmental chsnges in 108 (22,28%) cases, in 370 cases (77.78%) pathologic changes, like inflammatory changes of deciduas and chorionic villis in 302 cases (80.2%), pathologic prematurity of chorionic vili in 48 cases (12.6%), hydatidiform mole in 28 cases (7.4%). As most cases of pregnancy loss has been reported at 7-9 weeks /172 cases/, we compared histomorphologic data revealed at 7-8 (71 cases) weeks to 5-6 (135 cases) and 10-12 weeks of gestation. Morphologic research data confimed, that at 7-8 weeks compared to 5-6 weeks leading reason ofpregnancy loss was inflammatory changes (OR-1,584), what can be cause of 110 pregnancy losses at 1000 pregnant women (AR-0.11). Data comparing7-9 weeks to 10-12 weeks pregnancy losses, confirm the priority of pathologic immaturity (OR-1,279) and hydatidiform mole (OR-1,557) and could be the risk of 100 cases of pregnancy termination at 1000 pregnant women (AR-0.10).Existing results are of great importance for the preconceptional preparation of women.

Different radial growth responses of co-occurring coniferous forest trees in the Alps to drought

NASA Astrophysics Data System (ADS)

Oberhuber, Walter; Mennel, Julia

2010-05-01

Species-specific drought resistance will effect the development of forest ecosystems under a warmer and drier climate by changing species composition and inducing shifts in forest distribution. Therefore, we applied dendroclimatological techniques to determine drought sensitivity of three native coniferous tree species (Norway spruce, Picea abies; European larch, Larix decidua; Scots pine, Pinus sylvestris), which differ in phenological and successional traits and grow intermixed at dry-mesic sites within an inner-Alpine dry valley (750 m a.s.l., Tyrol, Austria). Ring-width chronologies (resolution 1 µm) of each species were developed by extracting two core samples from ≥ 80 mature trees (mean tree age 135 yr). To identify the climatic factors most closely associated with variations in radial tree growth, we calculated response and correlation functions for the common interval from 1911-2007 using yearly tree-ring indices and monthly and seasonal climate variables (precipitation, air temperature) and evaluated growth response to extreme hot and/or dry conditions during the growing season. Additionally, the impact of climate warming on long-term variability of climate-growth relationships was analysed by means of moving response functions. Major finding of our study were: (i) current April through June precipitation was the environmental factor most strongly associated with growth of all three species (r = 0.484, 0.458, and 0.546 for Pinus sylvestris, Larix decidua and Picea abies, respectively; all P < 0.001), whereby Picea abies showed higher correlation coefficients with precipitation from May through June (r = 0.585, P < 0.001). (ii) Annual increment of Picea abies was most strongly limited by May through June temperature (r = -0.500, P < 0.001). (iii) Continuously increasing moving response function coefficients of monthly precipitation variables since the mid-20th century revealed increasing drought sensitivity of all species. During recent decades a significant inverse relationship between radial growth and early summer temperature was only detected for Picea abies. (iv) Analysis of distinct below-average growth in several years (1952, 1976, 1984, 1992 and 2005) indicated species-specific response to climate extremes, whereby Pinus sylvestris was the least drought sensitive species of the comparison. Results demonstrate that within the study area different growth responses of coniferous species to climate exist, which might be explained by temporal shifts in cambial activity and wood formation. Furthermore, our study shows that high temperature and limited water availability has the strongest impact on the growth performance of Picea abies, which will likely lead to increased tree mortality. Instable climate-growth relationships during recent decades, which occur coincidently with the recent warming trend, indicate increasing drought stress of all species, whereby within mixed coniferous stands Pinus sylvestris may benefit from adapting better to drier conditions in the future. High mortality rates of Pinus sylvestris, which have been observed in recent years at more xeric sites, support our findings that drought initiates changes of forest structure and species composition within this dry inner-Alpine valley.

Gap junction connexins in female reproductive organs: implications for women's reproductive health.

PubMed

Winterhager, Elke; Kidder, Gerald M

2015-01-01

Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health. No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles. Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth. CX40, which characterizes the extravillous trophoblast (EVT), supports proliferation of the proximal EVTs while preventing them from differentiating into the invasive pathway. Furthermore, women with recurrent early pregnancy loss as well as those with endometriosis exhibit reduced levels of CX43 in their decidua. The antimalaria drug mefloquine, which blocks gap junction function, is responsible for increased risk of early pregnancy loss and stillbirth, probably due to inhibition of intercellular communication in the decidua or between trophoblast layers followed by an impairment of placental growth. Gap junctions also play a critical role in regulating uterine blood flow, contributing to the adaptive response to pregnancy. Given that reproductive impairment can result from connexin mutations in mice, it is advised that women suffering from somatic disease symptoms associated with connexin gene mutations be additionally tested for impacts on reproductive function. Better knowledge of these essential connexin functions in human female reproductive organs is important for safeguarding women's reproductive health. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding.

PubMed

Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Arlier, Sefa; Kayisli, Umit A; Lockwood, Charles J

2016-06-01

Human pregnancy requires robust hemostasis to prevent hemorrhage during extravillous trophoblast (EVT) invasion of the decidualized endometrium, modification of spiral arteries and post-partum processes. However, decidual hemorrhage (abruption) can occur throughout pregnancy from poorly transformed spiral arteries, causing fetal death or spontaneous preterm birth (PTB), or it can promote the aberrant placentation observed in intrauterine growth restriction (IUGR) and pre-eclampsia; all leading causes of perinatal or maternal morbidity and mortality. In non-fertile cycles, the decidua undergoes controlled menstrual bleeding. Abnormal uterine bleeding (AUB) accompanying progestin-only, long-acting, reversible contraception (pLARC) accounts for most discontinuations of these safe and highly effective agents, thereby contributing to unwanted pregnancies and abortion. The aim of this study was to investigate the role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. We conducted a critical review of the literature arising from PubMed searches up to December 2015, regarding in situ and in vitro expression and regulation of several specific proteins involved in uterine hemostasis in decidua and cycling endometrium. In addition, we discussed clinical and molecular mechanisms associated with pLARC-induced AUB and pregnancy complications with abruptions, chorioamnionitis or pre-eclampsia. Progestin-induced decidualization of estradiol-primed human endometrial stromal cells (HESCs) increases in vivo and in vitro expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) while inhibiting plasminogen activators (PAs), matrix metalloproteinases (MMPs), and the vasoconstrictor, endothelin-1 (ET-1). These changes in decidual cell-derived regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone prevent hemorrhage during EVT invasion and vascular remodeling. In non-fertile cycles, progesterone withdrawal reduces TF and PAI-1 while increasing PA, MMPs and ET-1, causing menstrual-associated bleeding, fibrinolysis, ECM degradation and ischemia. First trimester decidual hemorrhage elicits later adverse outcomes including pregnancy loss, pre-eclampsia, abruption, IUGR and PTB. Decidual hemorrhage generates excess thrombin that binds to decidual cell-expressed protease-activated receptors (PARs) to induce chemokines promoting shallow placentation; such bleeding later in pregnancy generates thrombin to down-regulate decidual cell progesterone receptors and up-regulate cytokines and MMPs linked to PTB. Endometria of pLARC users display ischemia-induced excess vasculogenesis and progestin inhibition of spiral artery vascular smooth muscle cell proliferation and migration leading to dilated fragile vessels prone to bleeding. Moreover, aberrant TF-derived thrombin signaling also contributes to the pathogenesis of endometriosis via induction of angiogenesis, inflammation and cell survival. Perivascular decidualized HESCs promote endometrial hemostasis during placentation yet facilitate menstruation through progestational regulation of hemostatic, proteolytic, and vasoactive proteins. Pathological endometrial hemorrhage elicits excess local thrombin generation, which contributes to pLARC associated AUB, endometriosis and adverse pregnancy outcomes through several biochemical mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding

PubMed Central

Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Arlier, Sefa; Kayisli, Umit A.; Lockwood, Charles J.

2016-01-01

BACKGROUND Human pregnancy requires robust hemostasis to prevent hemorrhage during extravillous trophoblast (EVT) invasion of the decidualized endometrium, modification of spiral arteries and post-partum processes. However, decidual hemorrhage (abruption) can occur throughout pregnancy from poorly transformed spiral arteries, causing fetal death or spontaneous preterm birth (PTB), or it can promote the aberrant placentation observed in intrauterine growth restriction (IUGR) and pre-eclampsia; all leading causes of perinatal or maternal morbidity and mortality. In non-fertile cycles, the decidua undergoes controlled menstrual bleeding. Abnormal uterine bleeding (AUB) accompanying progestin-only, long-acting, reversible contraception (pLARC) accounts for most discontinuations of these safe and highly effective agents, thereby contributing to unwanted pregnancies and abortion. The aim of this study was to investigate the role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. METHODS We conducted a critical review of the literature arising from PubMed searches up to December 2015, regarding in situ and in vitro expression and regulation of several specific proteins involved in uterine hemostasis in decidua and cycling endometrium. In addition, we discussed clinical and molecular mechanisms associated with pLARC-induced AUB and pregnancy complications with abruptions, chorioamnionitis or pre-eclampsia. RESULTS Progestin-induced decidualization of estradiol-primed human endometrial stromal cells (HESCs) increases in vivo and in vitro expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) while inhibiting plasminogen activators (PAs), matrix metalloproteinases (MMPs), and the vasoconstrictor, endothelin-1 (ET-1). These changes in decidual cell-derived regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone prevent hemorrhage during EVT invasion and vascular remodeling. In non-fertile cycles, progesterone withdrawal reduces TF and PAI-1 while increasing PA, MMPs and ET-1, causing menstrual-associated bleeding, fibrinolysis, ECM degradation and ischemia. First trimester decidual hemorrhage elicits later adverse outcomes including pregnancy loss, pre-eclampsia, abruption, IUGR and PTB. Decidual hemorrhage generates excess thrombin that binds to decidual cell-expressed protease-activated receptors (PARs) to induce chemokines promoting shallow placentation; such bleeding later in pregnancy generates thrombin to down-regulate decidual cell progesterone receptors and up-regulate cytokines and MMPs linked to PTB. Endometria of pLARC users display ischemia-induced excess vasculogenesis and progestin inhibition of spiral artery vascular smooth muscle cell proliferation and migration leading to dilated fragile vessels prone to bleeding. Moreover, aberrant TF-derived thrombin signaling also contributes to the pathogenesis of endometriosis via induction of angiogenesis, inflammation and cell survival. CONCLUSION Perivascular decidualized HESCs promote endometrial hemostasis during placentation yet facilitate menstruation through progestational regulation of hemostatic, proteolytic, and vasoactive proteins. Pathological endometrial hemorrhage elicits excess local thrombin generation, which contributes to pLARC associated AUB, endometriosis and adverse pregnancy outcomes through several biochemical mechanisms. PMID:26912000

Environmental control of CO2-assimilation and leaf conductance in Larix decidua Mill. : I. A comparison of contrasting natural environments.

PubMed

Benecke, U; Schulze, E -D; Matyssek, R; Havranek, W M

1981-08-01

CO 2 -assimilation and leaf conductance of Larix decidua Mill. were measured in the field at high (Patscherkofel, Austria) and low (Bayreuth, Germany) elevation in Europe, and outside its natural range along an altitudinal gradient in New Zealand.Phenology of leaf and stem growth showed New Zealand sites to have much longer growing seasons than in Europe, so that the timberline (1,330 m) season was almost twice as long as at the Austrian timberline (1,950 m).The maximum rates of photosynthesis, A max , were similar at all sites after completion of leaf growth, namely 3 to 3.5 μmol m -2 s -1 . Only the sun needles of the Bayreuth tree reached 3.5 to 5 μmol m -2 s -1 . Light response curves for CO 2 -assimilation changed during leaf ontogeny, the slope being less in young than in adult leaves. The temperature optimum for 90% of maximum photosynthesis was at all sites similar between ca. 12-28°C for much of the summer. Only at the cooler high altitude timberline sites were optima lower at ca. 10-16°C in developing needles during early summer.A linear correlation existed between A max and leaf conductance at A max , and this showed no difference between the sites except for sun needles at Bayreuth.Leaf conductance responded strongly to light intensity and this was concurrent with the light response of CO 2 -uptake. A short-term and a long-term effect were differentiated. With increasing age maximum rates of CO 2 -uptake and leaf conductance at A max increased, whereas short-term response during changes in light declined. The stomata became less responsive with increasing age and tended to remain open. The stomatal responses to light have a significant effect on the water use efficiency during diurnal courses. A higher water use efficiency was found for similar atmospheric conditions in spring than in autumn.Stomata responded with progressive closure to declining air humidity in a similar manner under dissimilar climates. Humidity response thus showed insensitivity to habitat differences.From the diurnal course of gas-exchange stomata were more closed at timberline (1,330 m) than at lower elevations but this did not lead to corresponding site differences in CO 2 -exchange suggesting Larix may not be operating at high water use efficiency when air is humid.The main difference between habitats studied was in the time necessary for completion of needle development. Similarity in photosynthesis and leaf conductance existed between sites when tree foliage was compared at the same stage of development. Length of growing season and time requirement for foliar development appear to be a principle factor in the carbon balance of deciduous species. The evergreen habit may be more effective in counterbalancing the effects of cool short summers.

Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

PubMed Central

Pavlov, Nadine; Guibourdenche, Jean; Degrelle, Séverine A.; Evain-Brion, Danièle

2014-01-01

The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

Placentation in the anteaters Myrmecophaga tridactyla and Tamandua tetradactyla (Eutheria, Xenarthra).

PubMed

Mess, Andrea M; Favaron, Phelipe O; Pfarrer, Christiane; Osmann, Christine; Melo, Allan P F; Rodrigues, Rosangela F; Ambrósio, Carlos E; Bevilacqua, Estela; Miglino, Maria A

2012-11-30

Since Xenarthra are serious candidates for being basal to Eutheria, their characteristics, e.g. the placental system, influence perceptions of evolution. However, in the subgroup containing the anteaters, data are very limited. The present study aims to elucidate the nature of the feto-maternal interface in the anteater placenta and to interpret these data within an evolutionary context. Placentas of two species were investigated with histology, immunohistochemistry and transmission electron microscopy. Remnants of the maternal vessel endothelium were absent, resulting in a fully haemochorial barrier throughout the placenta. Two structurally different parts, the villous and trabecular areas were complex and intermingled. In particular, the trabeculae which consisted of cellular, proliferative trophoblast, associated with connective tissue, were attached to the decidua. The villi contained fetal capillaries and hypertrophied mesenchymal cells that occurred near the surface near the end of gestation. The surface of the villi consisted of flat, syncytial trophoblast, interspersed with proliferative trophoblast cells. Based on fundamental differences between anteaters and armadillos, we inferred that placental evolution was more complex than previously thought. The haemochorial pattern of anteaters was likely an ancient condition of xenarthrans. Consequently, villous placentation may be attributed, at least in part, by convergent evolution, but was also characterized by some features that were widespread among xenarthrans.

Bark flammability as a fire-response trait for subalpine trees

PubMed Central

Frejaville, Thibaut; Curt, Thomas; Carcaillet, Christopher

2013-01-01

Relationships between the flammability properties of a given plant and its chances of survival after a fire still remain unknown. We hypothesize that the bark flammability of a tree reduces the potential for tree survival following surface fires, and that if tree resistance to fire is provided by a thick insulating bark, the latter must be few flammable. We test, on subalpine tree species, the relationship between the flammability of bark and its insulating ability, identifies the biological traits that determine bark flammability, and assesses their relative susceptibility to surface fires from their bark properties. The experimental set of burning properties was analyzed by Principal Component Analysis to assess the bark flammability. Bark insulating ability was expressed by the critical time to cambium kill computed from bark thickness. Log-linear regressions indicated that bark flammability varies with the bark thickness and the density of wood under bark and that the most flammable barks have poor insulating ability. Susceptibility to surface fires increases from gymnosperm to angiosperm subalpine trees. The co-dominant subalpine species Larix decidua (Mill.) and Pinus cembra (L.) exhibit large differences in both flammability and insulating ability of the bark that should partly explain their contrasted responses to fires in the past. PMID:24324473

High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography

NASA Astrophysics Data System (ADS)

Ren, Hugang; Avila, Cecilia; Kaplan, Cynthia; Pan, Yingtian

2011-11-01

Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness dDV ~ 92+/-38 μm), low-scattering chorion and trophoblast (CT, dCT ~ 150+/-67 μm), high-scattering subepithelial amnion (A, dA ~ 95+/-36 μm), and low-scattering epithelium (E, dE ~ 29+/-8 μm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses dMCP ranging from 24 to 615 μm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., dMCP>615 μm) because of its increased imaging depth.

The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

PubMed

López-Tello, Jorge; Arias-Álvarez, María; Jiménez-Martínez, Maria-Ángeles; Barbero-Fernández, Alicia; García-García, Rosa María; Rodríguez, María; Lorenzo, Pedro L; Torres-Rovira, Laura; Astiz, Susana; González-Bulnes, Antonio; Rebollar, Pilar G

2017-06-01

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

Neutrophil migration into the placenta: Good, bad or deadly?

PubMed Central

Giaglis, Stavros; Stoikou, Maria; Grimolizzi, Franco; Subramanian, Bibin Y.; van Breda, Shane V.; Hoesli, Irene; Lapaire, Olav; Hasler, Paul; Than, Nandor Gabor; Hahn, Sinuhe

2016-01-01

ABSTRACT Almost 2 decades have passed since the discovery that pregnancy is associated with a basal inflammatory state involving neutrophil activation, and that this is more overt in cases with preeclampsia, than in instances with sepsis. This pivotal observation paved the way for our report, made almost a decade ago, describing the first involvement of neutrophil extracellular traps (NETs) in a non-infectious human pathology, namely preeclampsia, where an abundance of these structures were detected directly in the placental intervillous space. Despite these remarkable findings, there remains a paucity of interest among reproductive biologists in further exploring the role or involvement of neutrophils in pregnancy and related pathologies. In this review we attempt to redress this deficit by highlighting novel recent findings including the discovery of a novel neutrophil subset in the decidua, the interaction of placental protein 13 (PP13) and neutrophils in modulating spiral artery modification, as well as the use of animal model systems to elucidate neutrophil function in implantation, gestation and parturition. These model systems have been particularly useful in identifying key components implicated in recurrent fetal loss, preeclampsia or new signaling molecules such as sphingolipids. Finally, the recent discovery that anti-phospolipid antibodies can trigger NETosis, supports our hypothesis that these structures may contribute to placental dysfunction in pertinent cases with recurrent fetal loss. PMID:26933824

Placentation in the anteaters Myrmecophaga tridactyla and Tamandua tetradactyla (Eutheria, Xenarthra)

PubMed Central

2012-01-01

Background Since Xenarthra are serious candidates for being basal to Eutheria, their characteristics, e.g. the placental system, influence perceptions of evolution. However, in the subgroup containing the anteaters, data are very limited. The present study aims to elucidate the nature of the feto-maternal interface in the anteater placenta and to interpret these data within an evolutionary context. Methods Placentas of two species were investigated with histology, immunohistochemistry and transmission electron microscopy. Results Remnants of the maternal vessel endothelium were absent, resulting in a fully haemochorial barrier throughout the placenta. Two structurally different parts, the villous and trabecular areas were complex and intermingled. In particular, the trabeculae which consisted of cellular, proliferative trophoblast, associated with connective tissue, were attached to the decidua. The villi contained fetal capillaries and hypertrophied mesenchymal cells that occured near the surface near the end of gestation. The surface of the villi consisted of flat, syncytial trophoblast, interspersed with proliferative trophoblast cells. Conclusions Based on fundamental differences between anteaters and armadillos, we inferred that placental evolution was more complex than previously thought. The haemochorial pattern of anteaters was likely an ancient condition of xenarthrans. Consequently, villous placentation may be attributed, at least in part, by convergent evolution, but was also characterized by some features that were widespread among xenarthrans. PMID:23199198

Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface

PubMed Central

Li, N.; Wu, H.M.; Hang, F.; Zhang, Y.S.; Li, M.J.

2017-01-01

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA. PMID:28902929

The Liver X Receptor in Correlation with Other Nuclear Receptors in Spontaneous and Recurrent Abortions

PubMed Central

Knabl, Julia; Pestka, Aurelia; Hüttenbrenner, Rebecca; Plösch, Torsten; Welbergen, Lena; Günthner-Biller, Maria

2013-01-01

The liver X receptors (LXRs) have been shown to be crucially involved in maternal-fetal cholesterol transport and placentation. The aim of this study was to investigate the expression pattern and frequency of LXR under normal physiological circumstances and in spontaneous abortion and/or recurrent miscarriage. A total of 29 (12 physiologic pregnancies/10 spontaneous abortions/7 recurrent miscarriages) human pregnancies in first trimester were analysed for LXR expression. Expression changes were evaluated by immunohistochemistry for receptor and quantitative RT-PCR (TaqMan) was performed to determine the level of LXR mRNA expression. We also stained for RXRα and PPARγ as possible heterodimers of LXR. LXR expression was downregulated in the syncytiotrophoblast of spontaneous abortion placentas compared to normal pregnancy. In recurrent miscarriage there was a trend for a downregulation. Decidua showed an even stronger downregulation in both groups. In the syncytiotrophoblast we found a positive correlation for the combination of LXR/PPARγ in abortions and a negative correlation for LXR/RXRα. In addition, double-immunofluorescence staining showed that LXR as well as RXRα and PPARγ are expressed by the extravillous trophoblast. Finally, RXRα and LXR showed coexpression in the same extravillous trophoblast cells. To conclude, our data show that LXR expression is decreased in miscarriage. PMID:23690759

Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface.

PubMed

Li, N; Wu, H M; Hang, F; Zhang, Y S; Li, M J

2017-09-12

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

Joining the immunological dots in recurrent miscarriage.

PubMed

Bansal, Amolak Singh

2010-11-01

While raised cellular immunity mediated by T helper (Th) 1 type cells may be harmful for the developing embryo/foetus, it is likely that Th2 type immunity may be helpful. The role of natural killer (NK) cells is presently underestimated, although they are clearly important in angiogenesis and the coordinated invasion of the decidua by the trophoblast. Deficient T regulatory cell (Treg) function is evident in women with recurrent miscarriage particularly when this occurs in early pregnancy. The role of the pro-inflammatory Th17 cells is presently unclear. However, early evidence suggests that excessive Th17 activity may promote miscarriage and preterm delivery. This may relate to the ability of these cells to produce those cytokines that encourage Th1 and NK cell activity. As such recurrent miscarriage may be caused not only by chromosomal abnormalities, autoimmunity and uterine abnormalities but also by subclinical uterine infection and inflammation which by stimulating interleukin 6 favours Th17 development over Tregs. This review examines the role of these different cells in early pregnancy and suggests a schema that may join the dots of the immunological puzzle called pregnancy. Finally, suggestions are made as to how inappropriate immunity in recurrent miscarriage may be down-regulated using currently available therapies. © 2010 John Wiley & Sons A/S.

Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity.

PubMed

Jadoon, Saima; Karim, Sabiha; Bin Asad, Muhammad Hassham Hassan; Akram, Muhammad Rouf; Khan, Abida Kalsoom; Malik, Arif; Chen, Chunye; Murtaza, Ghulam

2015-01-01

The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed.

Preliminary evaluation of the potential of tree-ring cellulose content as a novel supplementary proxy in dendroclimatology

NASA Astrophysics Data System (ADS)

Ziehmer, Malin M.; Nicolussi, Kurt; Schlüchter, Christian; Leuenberger, Markus

2018-02-01

Cellulose content (CC (%)) in tree rings is usually utilised as a tool to control the quality of the α-cellulose extraction from tree rings in the preparation of stable-isotope analysis in wooden tissues. Reported amounts of CC (%) are often limited to mean values per tree. For the first time, CC (%) series from two high-Alpine species, Larix decidua Mill. (European Larch, LADE) and Pinus cembra L. (Swiss stone pine, PICE) are investigated in modern wood samples and Holocene wood remains from the Early and mid-Holocene. Modern CC (%) series reveal a species-specific low-frequency trend independent of their sampling site over the past 150 years. Climate-cellulose relationships illustrate the ability of CC (%) to record temperature in both species but for slightly different periods within the growing season. The Holocene CC (%) series illustrate diverging low-frequency trends in both species, independent of sampling site characteristics (latitude, longitude and elevation). Moreover, potential age trends are not apparent in the two coniferous species. The arithmetic mean of CC (%) series in the Early and mid-Holocene indicate low CC (%) succeeding cold events. In conclusion, CC (%) in tree rings show high potential to be established as novel supplementary proxy in dendroclimatology.

Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

PubMed

Heusschen, Roy; Freitag, Nancy; Tirado-González, Irene; Barrientos, Gabriela; Moschansky, Petra; Muñoz-Fernández, Raquel; Leno-Durán, Ester; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M

2013-01-01

Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.

Corticotropin-Releasing Hormone Modulates Human Trophoblast Invasion through Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulation

PubMed Central

Bamberger, Ana-Maria; Minas, Vassilis; Kalantaridou, Sophia N.; Radde, Jessica; Sadeghian, Helen; Löning, Thomas; Charalampopoulos, Ioannis; Brümmer, Jens; Wagener, Christoph; Bamberger, Christoph M.; Schulte, Heinrich M.; Chrousos, George P.; Makrigiannakis, Antonis

2006-01-01

Abnormalities in the process of trophoblast invasion may result in abnormal placentation. Both the embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH), which promotes implantation. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is expressed in extravillous trophoblasts (EVTs) of normal human placenta, may also function in tro-phoblast/endometrial interactions. We investigated whether locally produced CRH plays a role in trophoblast invasion, primarily by regulating CEACAM1 expression. We examined cultures of freshly isolated human EVTs, which express CEACAM1, and an EVT-based hybridoma cell line, which is devoid of endogenous CEACAM1. CRH inhibited EVT invasion in Matrigel invasion assays, and this effect was blocked by the CRH receptor type 1 (CRHR1)-specific antagonist antalarmin. Additionally, CRH decreased CEACAM1 expression in EVTs in a dose-dependent manner. After transfection of the hybridoma cell line with a CEACAM1 expression vector, the invasiveness of these cells was strongly enhanced. This effect was inhibited by addition of blocking monoclonal antibody against CEACAM1. Furthermore, blocking of endogenous CEACAM1 in EVTs inhibited the invasive potential of these cells. Taken together these findings suggest that CRH inhibits trophoblast invasion by decreasing the expression of CEACAM1 through CRHR1, an effect that might be involved in the pathophysiology of clinical conditions, such as preeclampsia and placenta accreta. PMID:16400017

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

PubMed Central

Cha, Jeeyeon; Bartos, Amanda; Egashira, Mahiro; Haraguchi, Hirofumi; Saito-Fujita, Tomoko; Leishman, Emma; Bradshaw, Heather; Dey, Sudhansu K.; Hirota, Yasushi

2013-01-01

There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women. PMID:23979163

The oxygen isotope enrichment of leaf-exported assimilates--does it always reflect lamina leaf water enrichment?

PubMed

Gessler, Arthur; Brandes, Elke; Keitel, Claudia; Boda, Sonja; Kayler, Zachary E; Granier, André; Barbour, Margaret; Farquhar, Graham D; Treydte, Kerstin

2013-10-01

The oxygen stable isotope composition of plant organic matter (OM) (particularly of wood and cellulose in the tree ring archive) is valuable in studies of plant-climate interaction, but there is a lack of information on the transfer of the isotope signal from the leaf to heterotrophic tissues. We studied the oxygen isotopic composition and its enrichment above source water of leaf water over diel courses in five tree species covering a broad range of life forms. We tracked the transfer of the isotopic signal to leaf water-soluble OM and further to phloem-transported OM. Observed leaf water evaporative enrichment was consistent with values predicted from mechanistic models taking into account nonsteady-state conditions. While leaf water-soluble OM showed the expected (18)O enrichment in all species, phloem sugars were less enriched than expected from leaf water enrichment in Scots pine (Pinus sylvestris), European larch (Larix decidua) and Alpine ash (Eucalyptus delegatensis). Oxygen atom exchange with nonenriched water during phloem loading and transport, as well as a significant contribution of assimilates from bark photosynthesis, can explain these phloem (18)O enrichment patterns. Our results indicate species-specific uncoupling between the leaf water and the OM oxygen isotope signal, which is important for the interpretation of tree ring data. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Experimental soil warming shifts the fungal community composition at the alpine treeline.

PubMed

Solly, Emily F; Lindahl, Björn D; Dawes, Melissa A; Peter, Martina; Souza, Rômulo C; Rixen, Christian; Hagedorn, Frank

2017-07-01

Increased CO 2 emissions and global warming may alter the composition of fungal communities through the removal of temperature limitation in the plant-soil system, faster nitrogen (N) cycling and changes in the carbon (C) allocation of host plants to the rhizosphere. At a Swiss treeline featuring Larix decidua and Pinus uncinata, the effects of multiple years of CO 2 enrichment and experimental soil warming on the fungal community composition in the organic horizons were analysed using 454-pyrosequencing of ITS2 amplicons. Sporocarp production and colonization of ectomycorrhizal root tips were investigated in parallel. Fungal community composition was significantly altered by soil warming, whereas CO 2 enrichment had little effect. Tree species influenced fungal community composition and the magnitude of the warming responses. The abundance of ectomycorrhizal fungal taxa was positively correlated with N availability, and ectomycorrhizal taxa specialized for conditions of high N availability proliferated with warming, corresponding to considerable increases in inorganic N in warmed soils. Traits related to N utilization are important in determining the responses of ectomycorrhizal fungi to warming in N-poor cold ecosystems. Shifts in the overall fungal community composition in response to higher temperatures may alter fungal-driven processes with potential feedbacks on ecosystem N cycling and C storage at the alpine treeline. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion

PubMed Central

Nakashima, Akitoshi; Shiozaki, Arihiro; Myojo, Subaru; Ito, Mika; Tatematsu, Mikiko; Sakai, Masatoshi; Takamori, Yasushi; Ogawa, Kazuyuki; Nagata, Kinya; Saito, Shigeru

2008-01-01

Immune changes are known to occur in recurrent spontaneous abortion, but it is unclear whether either maternal natural killer (NK) cells or T cells attack fetus-derived trophoblasts. To clarify the immunological causes of spontaneous abortion, we examined the relationship between cytotoxic granule proteins in decidual lymphocytes, such as granulysin, granzyme B, and perforin, and the induction of apoptosis in extravillous trophoblasts (EVTs). The number of granulysin-positive CD56bright NK cells increased significantly in the decidua basalis during spontaneous abortion compared with normal pregnancy; however, granzyme B- and perforin-positive cells did not change. Interestingly, the expression of granulysin was also detected in the nuclei of EVTs in spontaneous abortion samples. When IL-2-stimulated CD56bright NK cells were cocultured with EVT cells (HTR-8/SV40neo), granulysin was found initially in the cytoplasm and then accumulated in the nuclei of the HTR-8/SV40neo cells. Furthermore, transfected cells expressing a GFP-granulysin fusion protein induced apoptosis in HTR-8/SV40neo cells independently of caspases. Our results suggest that granulysin-positive uterine NK cells attack EVTs; subsequently, the uNK-derived granulysin actively accumulates in the nuclei of EVTs, causing the death of EVTs due to apoptosis. These data support a new apoptosis pathway for trophoblasts via uNK-derived granulysin, suggesting that granulysin is involved in spontaneous abortion. PMID:18688023

RXRα is Upregulated in First Trimester Endometrial Glands of Spontaneous Abortions Unlike LXR and PPARγ

PubMed Central

Knabl, J.; Vattai, A.; Hüttenbrenner, R.; Hutter, S.; Karsten, M.

2016-01-01

Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analyzed for expression of the nuclear receptors LXR, RXRα and PPARγ. Expression changes were evaluated by immunohistochemistry in decidual tissue and endometrial glands of the decidua. RXRα expression was up-regulated in the endometrial glands of spontaneous abortion (P<0.015). Similar up regulation of RXRα was found in decidual tissue (P<0.05). LXR and PPARγ expression was unchanged in spontaneous abortion. By Correlation analysis we found a trend to positive correlation of LXR and PPARγ (Spearman correlation coefficient r=0.56, P=0.07) in endometrial glands. In decidual tissue, we found significant negative correlation in the control group, for the combination of RXRα and PPARγ (Spearman correlation coefficient r=0.913, P=0.03). Our data show that RXRα expression is increased in miscarriage in endometrial glands and correlation analysis showed that negative correlation between RXRα and PPARγ disappears in miscarriage. This shift is supposable responsible for the loss of regular function in trophoblast and embryonic tissue. PMID:28076928

A review of techniques of induced abortion.

PubMed

Hepburn, S

1981-04-01

Various techniques are available for inducing abortion. Evacuation of the uterus through the vagina is generally the preferred method in first trimester pregnancies. Dilation of the cervical canal by inserting rod dilators or laminaria tents allows the withdrawal of the fetus. Suction procedures (vacuum aspiration, uterine aspiration, or suction curettage) are possible since the decidua are separable from the basal layer of endometrium. This removal by force does not damage other maternal tissue. A cannula is introduced into the uterine cavity through the dilated cervix and its operator is then connected to a pump by way of a flexible tube which delivers negative pressure of about 600 mm of mercury. When the fetus is withdrawn, the uterus is felt to contract onto the cannula. The average time for this procedure is 5 minutes. Surgical curettage or dilatation and evacuation first dilates the cervical canal and then removes fetal parts and tissue from ovum forceps; a sharp curette does the rest. Anesthesia for these procedures may be general, local, or spinal. The techniques of menstrual regulation is used before pregnancy can be confirmed. However with the advent of the RIA test for the beta subunit of HCG this procedure is rarely indicated. Induction of premature labor is used in the later 1/2 of the second trimester and utilizes prostaglandins. Intraamniobor usually begins within 24 hours. Hysterotomy and hysterectomy are surgical procedures used in abortions.

Sustained Endocannabinoid Signaling Compromises Decidual Function and Promotes Inflammation-induced Preterm Birth.

PubMed

Sun, Xiaofei; Deng, Wenbo; Li, Yingju; Tang, Shuang; Leishman, Emma; Bradshaw, Heather B; Dey, Sudhansu K

2016-04-08

Recent studies provide evidence that premature maternal decidual senescence resulting from heightened mTORC1 signaling is a cause of preterm birth (PTB). We show here that mice devoid of fatty acid amide hydrolase (FAAH) with elevated levels ofN-arachidonyl ethanolamide (anandamide), a major endocannabinoid lipid mediator, were more susceptible to PTB upon lipopolysaccharide (LPS) challenge. Anandamide is degraded by FAAH and primarily works by activating two G-protein-coupled receptors CB1 and CB2, encoded by Cnr1 and Cnr2, respectively. We found thatFaah(-/-)decidual cells progressively underwent premature senescence as marked by increased senescence-associated β-galactosidase (SA-β-Gal) staining and γH2AX-positive decidual cells. Interestingly, increased endocannabinoid signaling activated MAPK p38, but not p42/44 or mTORC1 signaling, inFaah(-/-)deciduae, and inhibition of p38 halted premature decidual senescence. We further showed that treatment of a long-acting anandamide in wild-type mice at midgestation triggered premature decidual senescence utilizing CB1, since administration of a CB1 antagonist greatly reduced the rate of PTB inFaah(-/-)females exposed to LPS. These results provide evidence that endocannabinoid signaling is critical in regulating decidual senescence and parturition timing. This study identifies a previously unidentified pathway in decidual senescence, which is independent of mTORC1 signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A study of monoamine oxidase activity in fetal membranes.

PubMed

Sekizawa, A; Ishikawa, H; Morimoto, T; Hirose, K; Suzuki, A; Saito, H; Yanaihara, T; Arai, Y; Oguchi, K

1996-05-01

To study the role of decidual monoamine oxidase (MAO)-A and -B activities before delivery, the relationship between MAO activity in fetal membranes and catecholamine (CA) concentration in amniotic fluid (AF) was determined. Fetal membranes and AF were obtained at the time of elective Cesarean section (CS group, n = 11) and Cesarean section due to fetal distress without labor pains (FD group, n = 5). MAO-A and -B activities were radiometrically measured using 14C-5-hydroxytriptamine for MAO-A substrate and 14C-benzylamine for MAO-B substrate. CA concentrations in AF were measured by high performance liquid chromatograph with an electro-chemical detector. Both MAO-A and -B activities in decidua obtained from CS were significantly lower than those obtained from FD. Both norepinephrine (NE) and epinephrine (EP) concentrations were significantly lower in the CS group than the FD group. A significant positive correlation between decidual MAO-A activity and NE concentration in AF was observed. No significant correlation was observed between MAO-B activity and the concentration of NE in AF. There was no correlation between EP concentrations and MAO activities. These results suggest that CA concentration in AF may be related to the activity of MAO in fetal membranes, determined by certain physiological processes during pregnancy. It has been suggested that metabolism of monoamines in fetal membranes also plays an important role in reducing monoamine influx into maternal myometrium from the AF.

A new late glacial to early Holocene palaeobotanical and archaeological record in the Eastern Pre-Alps: the Palughetto basin (Cansiglio Plateau, Italy)

NASA Astrophysics Data System (ADS)

Avigliano, Roberto; di Anastasio, Giulio; Improta, Salvatore; Peresani, Marco; Ravazzi, Cesare

2000-12-01

A late glacial to early Holocene lacustrine and peat succession, rich in conifer remains and including some palaeolithic flint artefacts, has been investigated in the Palughetto intermorainic basin (Venetian Pre-Alps). The geomorphological and stratigraphical relationships, 14C dates and pollen analyses allow a reconstruction of the environmental history of the basin and provide significant insights into the reforestation and peopling of the Pre-Alps. The onset of peat accumulation is dated to 14.4-14.1 kyr cal. BP, coinciding with reforestation at middle altitudes that immediately post-dates the immigration of Larix decidua and Picea abies subsp. europaea. Plant macrofossils point to the expansion of spruce about 14.3 kyr cal. BP, so far one of the earliest directly dated in the late glacial period of southern Europe. The previous hypothesis of an early Holocene spruce immigration in the Southern Alps from Slovenia needs reconsideration. Organic sedimentation stopped at the end of the Younger Dryas and was followed by the evolution of hydromorphic soils containing lithic artefacts, anthropic structures and wood charcoal. The typological features of the flint implements refer human occupation of the site to the end of the recent Epigravettian. Charcoals yielded dates either consistent with, or younger than, the archaeological chronology, in the early and middle Holocene.

The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

PubMed

Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

2000-01-01

The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity

PubMed Central

Karim, Sabiha; Asad, Muhammad Hassham Hassan Bin; Kalsoom Khan, Abida; Malik, Arif; Chen, Chunye

2015-01-01

The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed. PMID:26448818

Plasticity in gas-exchange physiology of mature Scots pine and European larch drive short- and long-term adjustments to changes in water availability.

PubMed

Feichtinger, Linda M; Siegwolf, Rolf T W; Gessler, Arthur; Buchmann, Nina; Lévesque, Mathieu; Rigling, Andreas

2017-09-01

Adjustment mechanisms of trees to changes in soil-water availability over long periods are poorly understood, but crucial to improve estimates of forest development in a changing climate. We compared mature trees of Scots pine (Pinus sylvestris) and European larch (Larix decidua) growing along water-permeable channels (irrigated) and under natural conditions (control) at three sites in inner-Alpine dry valleys. At two sites, the irrigation had been stopped in the 1980s. We combined measurements of basal area increment (BAI), tree height and gas-exchange physiology (Δ 13 C) for the period 1970-2009. At one site, the Δ 13 C of irrigated pine trees was higher than that of the control in all years, while at the other sites, it differed in pine and larch only in years with dry climatic conditions. During the first decade after the sudden change in water availability, the BAI and Δ 13 C of originally irrigated pine and larch trees decreased instantly, but subsequently reached higher levels than those of the control by 2009 (15 years afterwards). We found a high plasticity in the gas-exchange physiology of pine and larch and site-specific responses to changes in water availability. Our study highlights the ability of trees to adjust to new conditions, thus showing high resilience. © 2017 John Wiley & Sons Ltd.

How much does climate change threaten European forest tree species distributions?

PubMed

Dyderski, Marcin K; Paź, Sonia; Frelich, Lee E; Jagodziński, Andrzej M

2018-03-01

Although numerous species distribution models have been developed, most were based on insufficient distribution data or used older climate change scenarios. We aimed to quantify changes in projected ranges and threat level by the years 2061-2080, for 12 European forest tree species under three climate change scenarios. We combined tree distribution data from the Global Biodiversity Information Facility, EUFORGEN, and forest inventories, and we developed species distribution models using MaxEnt and 19 bioclimatic variables. Models were developed for three climate change scenarios-optimistic (RCP2.6), moderate (RCP4.5), and pessimistic (RPC8.5)-using three General Circulation Models, for the period 2061-2080. Our study revealed different responses of tree species to projected climate change. The species may be divided into three groups: "winners"-mostly late-successional species: Abies alba, Fagus sylvatica, Fraxinus excelsior, Quercus robur, and Quercus petraea; "losers"-mostly pioneer species: Betula pendula, Larix decidua, Picea abies, and Pinus sylvestris; and alien species-Pseudotsuga menziesii, Quercus rubra, and Robinia pseudoacacia, which may be also considered as "winners." Assuming limited migration, most of the species studied would face a significant decrease in suitable habitat area. The threat level was highest for species that currently have the northernmost distribution centers. Ecological consequences of the projected range contractions would be serious for both forest management and nature conservation. © 2017 John Wiley & Sons Ltd.

Different characteristics of mesenchymal stem cells isolated from different layers of full term placenta

PubMed Central

Ha, Chul-Won; Kim, Jin A; Heo, Jin-Chul; Han, Woo-Jung; Oh, Soo-Young; Choi, Suk-Joo

2017-01-01

Background The placenta is a very attractive source of mesenchymal stem cells (MSCs) for regenerative medicine due to readily availability, non-invasive acquisition, and avoidance of ethical issues. Isolating MSCs from parts of placenta tissue has obtained growing interest because they are assumed to exhibit different proliferation and differentiation potentials due to complex structures and functions of the placenta. The objective of this study was to isolate MSCs from different parts of the placenta and compare their characteristics. Methods Placenta was divided into amniotic epithelium (AE), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV), chorionic trophoblast without villi (CT-V), decidua (DC), and whole placenta (Pla). Cells isolated from each layer were subjected to analyses for their morphology, proliferation ability, surface markers, and multi-lineage differentiation potential. MSCs were isolated from all placental layers and their characteristics were compared. Findings Surface antigen phenotype, morphology, and differentiation characteristics of cells from all layers indicated that they exhibited properties of MSCs. MSCs from different placental layers had different proliferation rates and differentiation potentials. MSCs from CM, CT-V, CV, and DC had better population doubling time and multi-lineage differentiation potentials compared to those from other layers. Conclusions Our results indicate that MSCs with different characteristics can be isolated from all layers of term placenta. These finding suggest that it is necessary to appropriately select MSCs from different placental layers for successful and consistent outcomes in clinical applications. PMID:28225815

The Role of Progesterone in the Feto-Maternal Immunological Crosstalk.

PubMed

Szekeres-Bartho, Julia

2018-06-27

This review aims to provide a brief historical overview of the feto-maternal immunological relationship, which profoundly influences the outcome of pregnancy. The initial question posed in the nineteen fifties by Medawar, was based on the assumption that the maternal immune system recognizes the fetus as an allograft. Indeed, based on the association between HLA-matching and spontaneous miscarriage, it became obvious that immunological recognition of pregnancy is required for a successful gestation. The restricted expression of polymorphic HLA antigens on the trophoblast, together with the presence of non-polymorphic MHC products excludes recognition by both T and NK cells of trophoblast presented antigens, however, T cells, which constitute the majority of decidual T cells are likely candidates. Indeed, a high number of activated, progesterone receptor-expressing T cells are present in peripheral blood of healthy pregnant women, and in the presence of progesterone, these cells secrete an immunomodulatory protein called Progesterone-induced Blocking Factor or PIBF. As early as in the peri-implantation period, the embryo communicates with the maternal immune system via PIBF containing extracellular vesicles. PIBF contributes to the dominance of Th2-type reactivity characterising normal pregnancy, by inducing increased production of Th2 cytokines. The high expression of this molecule in the decidua might be one of the reasons for the low cytotoxic activity of decidual NK cells. ©2018The Author(s). Published by S. Karger AG, Basel.

Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses.

PubMed

Tse, J Y; Lao, T T; Chan, C C; Chiu, P M; Cheung, A N

2001-01-01

Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.

Tree-ring proxies of larch bud moth defoliation: latewood width and blue intensity are more precise than tree-ring width.

PubMed

Arbellay, Estelle; Jarvis, Ingrid; Chavardès, Raphaël D; Daniels, Lori D; Stoffel, Markus

2018-05-19

Reconstructions of defoliation by larch bud moth (LBM, Zeiraphera diniana Gn.) based on European larch (Larix decidua Mill.) tree rings have unraveled outbreak patterns over exceptional temporal and spatial scales. In this study, we conducted tree-ring analyses on 105 increment cores of European larch from the Valais Alps, Switzerland. The well-documented history of LBM outbreaks in Valais provided a solid baseline for evaluating the LBM defoliation signal in multiple tree-ring parameters. First, we used tree-ring width measurements along with regional records of LBM outbreaks to reconstruct the occurrence of these events at two sites within the Swiss Alps. Second, we measured earlywood width, latewood width and blue intensity, and compared these parameters with tree-ring width to assess the capacity of each proxy to detect LBM defoliation. A total of six LBM outbreaks were reconstructed for the two sites between AD 1850 and 2000. Growth suppression induced by LBM was, on average, highest in latewood width (59%), followed by total ring width (54%), earlywood width (51%) and blue intensity (26%). We show that latewood width and blue intensity can improve the temporal accuracy of LBM outbreak reconstructions, as both proxies systematically detected LBM defoliation in the first year it occurred, as well as the differentiation between defoliation and non-defoliation years. This study introduces blue intensity as a promising new proxy of insect defoliation and encourages its use in conjunction with latewood width.

11β-hydroxysteroid dehydrogenase type 1 and pregnancy: Role in the timing of labour onset and in myometrial contraction.

PubMed

Damiani, Francesco; Makieva, Sofia; Rinaldi, Sara F; Hua, Lei; Marcolongo, Paola; Petraglia, Felice; Norman, Jane E

2017-05-15

Glucocorticoids play a primary role in the maturation of fetal organs and may contribute to the onset of labour. Glucocorticoid activity depends on the 11β-hydroxysteroid dehydrogenase family (11β-HSDs), catalysing the interconversion between "active" cortisol into inactive cortisone. No definitive study exists on 11β-HSD expression profile in human decidua and myometrium during pregnancy. We investigated the implications of 11β-HSD1 in the regulation of uterine activity in pregnancy, examining its role on contraction of a myocyte cell line and murine 11β-hsd1 levels in utero. Murine 11β-hsd1 mRNA and protein levels in utero progressively increased until the last day of gestation and significantly decreased at the onset of labour (P < 0.0001) (n = 3 to 5 in the various gestational days analysed). Experiments on human myometrial samples confirm the significant fall in 11β-hsd1 mRNA levels at labour, compared to end pregnancy samples (n = 5 to 8). In vitro experiments showed that human myometrial contraction is inhibited by using a non-selective inhibitor of 11β-HSD1. The present study shows the temporal localisation of 11β-HSD1 in uterus, highlighting its importance in the timing of gestation and suggesting its contribution in the myometrium contraction. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas.

PubMed

Singal, Sahil S; Nygard, Karen; Gratton, Robert; Jansson, Thomas; Gupta, Madhulika B

2018-05-01

Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.

Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature

PubMed Central

Vazquez-Martin, Alejandro; Anatskaya, Olga V.; Giuliani, Alessandro; Erenpreisa, Jekaterina; Huang, Sui; Salmina, Kristine; Inashkina, Inna; Huna, Anda; Nikolsky, Nikolai N.; Vinogradov, Alexander E.

2016-01-01

The dependence of cancer on overexpressed c-MYC and its predisposition for polyploidy represents a double puzzle. We address this conundrum by cross-species transcription analysis of c-MYC interacting genes in polyploid vs. diploid tissues and cells, including human vs. mouse heart, mouse vs. human liver and purified 4n vs. 2n mouse decidua cells. Gene-by-gene transcriptome comparison and principal component analysis indicated that c-MYC interactants are significantly overrepresented among ploidy-associated genes. Protein interaction networks and gene module analysis revealed that the most upregulated genes relate to growth, stress response, proliferation, stemness and unicellularity, as well as to the pathways of cancer supported by MAPK and RAS coordinated pathways. A surprising feature was the up-regulation of epithelial-mesenchymal transition (EMT) modules embodied by the N-cadherin pathway and EMT regulators from SNAIL and TWIST families. Metabolic pathway analysis also revealed the EMT-linked features, such as global proteome remodeling, oxidative stress, DNA repair and Warburg-like energy metabolism. Genes associated with apoptosis, immunity, energy demand and tumour suppression were mostly down-regulated. Noteworthy, despite the association between polyploidy and ample features of cancer, polyploidy does not trigger it. Possibly it occurs because normal polyploidy does not go that far in embryonalisation and linked genome destabilisation. In general, the analysis of polyploid transcriptome explained the evolutionary relation of c-MYC and polyploidy to cancer. PMID:27655693

Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy.

PubMed

Smith, Samantha D; Dunk, Caroline E; Aplin, John D; Harris, Lynda K; Jones, Rebecca L

2009-05-01

Decidual artery remodeling is essential for a healthy pregnancy. This process involves loss of vascular smooth muscle cells and endothelium, which are replaced by endovascular trophoblasts (vEVTs) embedded in fibrinoid. Remodeling is impaired during pre-eclampsia, a disease of pregnancy that results in maternal and fetal mortality and morbidity. Early vascular changes occur in the absence of vEVTs, suggesting that another cell type is involved; evidence from animal models indicates that decidual leukocytes play a role. We hypothesized that leukocytes participate in remodeling through the triggering of apoptosis or extracellular matrix degradation. Decidua basalis samples (8 to 12 weeks gestation) were examined by immunohistochemistry to elucidate associations between leukocytes, vEVTs, and key remodeling events. Trophoblast-independent and -dependent phases of remodeling were identified. Based on a combination of morphological attributes, vessel profiles were classified into a putative temporal series of four stages. In early stages of remodeling, vascular smooth muscle cells showed dramatic disruption and disorganization before vEVT presence. Leukocytes (identified as uterine natural killer cells and macrophages) were apparent infiltrating vascular smooth muscle cells layers and were matrix metalloproteinase-7 and -9 immunopositive. A proportion of vascular smooth muscle cells and endothelial cells were terminal deoxynucleotidyl transferase dUTP nick-end labeling positive, suggesting remodeling involves apoptosis. We thus confirm that vascular remodeling occurs in distinct trophoblast-independent and -dependent stages and provide the first evidence of decidual leukocyte involvement in trophoblast-independent stages.

The sonographic appearance and obstetric management of placenta accreta

PubMed Central

Cheung, Charleen Sze-yan; Chan, Ben Chong-pun

2012-01-01

Placenta accreta is a condition of abnormal placental implantation in which the placental tissue invades beyond the decidua basalis. It may invade into or even through the myometrium and adjacent organs, such as the urinary bladder. The incidence has been rising in recent years. It is one of the important obstetric complications nowadays, leading to significant maternal morbidity and mortality. In the past, this condition was often diagnosed at the time of delivery when massive and unexpected hemorrhage occurred. Hysterectomy, associated with significant physical and psychological consequences, was usually the only management option. As more obstetricians have become aware of this condition, early identification with antenatal imaging diagnostic technology has become possible. Ultrasound scan plays an important role in the antenatal diagnosis. Various sonographic features with different specificity and sensitivity have been described in the literature. In equivocal cases, magnetic resonance imaging may be helpful. With such information, more accurate counseling can be offered to the mothers and their families before delivery. The delivery can also be arranged at a favorable time and in an institution where multidisciplinary support is available. Input from a hematologist, interventional radiologist, intensive care physician, urology surgeon, and/or other specialist are desirable. Apart from hysterectomy, various forms of conservative management can also be considered when the diagnosis is made prior to delivery. Fertility can therefore be preserved. After delivery, with or without hysterectomy performed, psychological support to the mothers and their families is essential. PMID:23239929

Immune cells in term and preterm labor

PubMed Central

Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

2014-01-01

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

Maternal uterine NK cell–activating receptor KIR2DS1 enhances placentation

PubMed Central

Xiong, Shiqiu; Sharkey, Andrew M.; Kennedy, Philippa R.; Gardner, Lucy; Farrell, Lydia E.; Chazara, Olympe; Bauer, Julien; Hiby, Susan E.; Colucci, Francesco; Moffett, Ashley

2013-01-01

Reduced trophoblast invasion and vascular conversion in decidua are thought to be the primary defect of common pregnancy disorders including preeclampsia and fetal growth restriction. Genetic studies suggest these conditions are linked to combinations of polymorphic killer cell Ig-like receptor (KIR) genes expressed by maternal decidual NK cells (dNK) and HLA-C genes expressed by fetal trophoblast. Inhibitory KIR2DL1 and activating KIR2DS1 both bind HLA-C2, but confer increased risk or protection from pregnancy disorders, respectively. The mechanisms underlying these genetic associations with opposing outcomes are unknown. We show that KIR2DS1 is highly expressed in dNK, stimulating strong activation of KIR2DS1+ dNK. We used microarrays to identify additional responses triggered by binding of KIR2DS1 or KIR2DL1 to HLA-C2 and found different responses in dNK coexpressing KIR2DS1 with KIR2DL1 compared with dNK only expressing KIR2DL1. Activation of KIR2DS1+ dNK by HLA-C2 stimulated production of soluble products including GM-CSF, detected by intracellular FACS and ELISA. We demonstrated that GM-CSF enhanced migration of primary trophoblast and JEG-3 trophoblast cells in vitro. These findings provide a molecular mechanism explaining how recognition of HLA class I molecules on fetal trophoblast by an activating KIR on maternal dNK may be beneficial for placentation. PMID:24091323

Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells

PubMed Central

Penna, Ivan; Du, Hongling; Ferriani, Rui; Taylor, Hugh S.

2008-01-01

Calpains have been implicated in the regulation of apoptosis. Here, we identified Calpain5 as a target of HOXA10 transcriptional regulation in endometrial cells as well as its aberrant regulation in endometriosis. Histologically confirmed biopsies of endometriosis were obtained from 20 women. Eutopic endometrium was collected by endometrial biopsy from 30 controls and from the 20 subjects with endometriosis. First trimester decidual samples were obtained from five subjects at the time of pregnancy termination. Immunohistochemistry was used to identify Calpain5 expression. Calpain5 was expressed in endometrial stromal and glandular cells throughout the menstrual cycle and in decidua. Calpain5 protein expression was decreased in both stromal and glandular cells from women with endometriosis compared with that of fertile controls. Human endometrial stromal and epithelial cell lines were transfected with pcDNA/HOXA10, HOXA10 siRNA or respective controls. Quantitative real-time RT–PCR was performed to determine expression of HOXA10 and Calpain5 in each group. Transfection of HESC cells with an HOXA10 expression construct led to increased Calpain5 expression, whereas transfection with siRNA resulted in decreased expression. In conclusion, Calpain5 expression is regulated by HOXA10. Calpain5 expression was decreased in endometriosis likely as a result of decreased HOXA10 expression. Decreased apoptosis in endometrial cells may promote the development of endometriosis through a pathway involving HOXA10, Calpain5 and caspase. PMID:18829447

Balanced levels of nerve growth factor are required for normal pregnancy progression.

PubMed

Frank, Pierre; Barrientos, Gabriela; Tirado-González, Irene; Cohen, Marie; Moschansky, Petra; Peters, Eva M; Klapp, Burghard F; Rose, Matthias; Tometten, Mareike; Blois, Sandra M

2014-08-01

Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P(+) nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation. © 2014 Society for Reproduction and Fertility.

Differential Spatiotemporal Patterns of Galectin Expression are a Hallmark of Endotheliochorial Placentation.

PubMed

Conrad, Melanie L; Freitag, Nancy; Diessler, Mónica E; Hernandez, Rocío; Barrientos, Gabriela; Rose, Matthias; Casas, Luciano A; Barbeito, Claudio G; Blois, Sandra M

2016-03-01

Galectins influence the progress of pregnancy by regulating key processes associated with embryo-maternal cross talk, including angiogenesis and placentation. Galectin family members exert multiple roles in the context of hemochorial and epitheliochorial placentation; however, the galectin prolife in endotheliochorial placenta remains to be investigated. Here, we used immunohistochemistry to analyze galectin (gal)-1, gal-3 and gal-9 expression during early and late endotheliochorial placentation in two different species (dogs and cats). We found that during early feline gestation, all three galectin members were more strongly expressed on trophoblast and maternal vessels compared to the decidua. This was accompanied by an overall decrease of gal-1, gal-3 and gal-9 expressions in late feline gestation. In canine early pregnancy, we observed that gal-1 and gal-9 were expressed strongly in cytotrophoblast (CTB) cells compared to gal-3, and no galectin expression was observed in syncytiotrophoblast (STB) cells. Progression of canine gestation was accompanied by increased gal-1 and gal-3 expressions on STB cells, whereas gal-9 expression remained similar in CTB and STB. These data suggest that both the maternal and fetal compartments are characterized by a spatiotemporal regulation of galectin expression during endotheliochorial placentation. This strongly suggests the involvement of the galectin family in important developmental processes during gestation including immunemodulation, trophoblast invasion and angiogenesis. A conserved functional role for galectins during mammalian placental development emerges from these studies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative chloroplast genomics reveals the evolution of Pinaceae genera and subfamilies.

PubMed

Lin, Ching-Ping; Huang, Jen-Pan; Wu, Chung-Shien; Hsu, Chih-Yao; Chaw, Shu-Miaw

2010-01-01

As the largest and the basal-most family of conifers, Pinaceae provides key insights into the evolutionary history of conifers. We present comparative chloroplast genomics and analysis of concatenated 49 chloroplast protein-coding genes common to 19 gymnosperms, including 15 species from 8 Pinaceous genera, to address the long-standing controversy about Pinaceae phylogeny. The complete cpDNAs of Cathaya argyrophylla and Cedrus deodara (Abitoideae) and draft cpDNAs of Larix decidua, Picea morrisonicola, and Pseudotsuga wilsoniana are reported. We found 21- and 42-kb inversions in congeneric species and different populations of Pinaceous species, which indicates that structural polymorphics may be common and ancient in Pinaceae. Our phylogenetic analyses reveal that Cedrus is clustered with Abies-Keteleeria rather than the basal-most genus of Pinaceae and that Cathaya is closer to Pinus than to Picea or Larix-Pseudotsuga. Topology and structural change tests and indel-distribution comparisons lend further evidence to our phylogenetic finding. Our molecular datings suggest that Pinaceae first evolved during Early Jurassic, and diversification of Pinaceous subfamilies and genera took place during Mid-Jurassic and Lower Cretaceous, respectively. Using different maximum-likelihood divergences as thresholds, we conclude that 2 (Abietoideae and Larix-Pseudotsuga-Piceae-Cathaya-Pinus), 4 (Cedrus, non-Cedrus Abietoideae, Larix-Pseudotsuga, and Piceae-Cathaya-Pinus), or 5 (Cedrus, non-Cedrus Abietoideae, Larix-Pseudotsuga, Picea, and Cathaya-Pinus) groups/subfamilies are more reasonable delimitations for Pinaceae. Specifically, our views on subfamilial classifications differ from previous studies in terms of the rank of Cedrus and with recognition of more than two subfamilies.

Comparative Chloroplast Genomics Reveals the Evolution of Pinaceae Genera and Subfamilies

PubMed Central

Lin, Ching-Ping; Huang, Jen-Pan; Wu, Chung-Shien; Hsu, Chih-Yao; Chaw, Shu-Miaw

2010-01-01

As the largest and the basal-most family of conifers, Pinaceae provides key insights into the evolutionary history of conifers. We present comparative chloroplast genomics and analysis of concatenated 49 chloroplast protein-coding genes common to 19 gymnosperms, including 15 species from 8 Pinaceous genera, to address the long-standing controversy about Pinaceae phylogeny. The complete cpDNAs of Cathaya argyrophylla and Cedrus deodara (Abitoideae) and draft cpDNAs of Larix decidua, Picea morrisonicola, and Pseudotsuga wilsoniana are reported. We found 21- and 42-kb inversions in congeneric species and different populations of Pinaceous species, which indicates that structural polymorphics may be common and ancient in Pinaceae. Our phylogenetic analyses reveal that Cedrus is clustered with Abies–Keteleeria rather than the basal-most genus of Pinaceae and that Cathaya is closer to Pinus than to Picea or Larix–Pseudotsuga. Topology and structural change tests and indel-distribution comparisons lend further evidence to our phylogenetic finding. Our molecular datings suggest that Pinaceae first evolved during Early Jurassic, and diversification of Pinaceous subfamilies and genera took place during Mid-Jurassic and Lower Cretaceous, respectively. Using different maximum-likelihood divergences as thresholds, we conclude that 2 (Abietoideae and Larix–Pseudotsuga–Piceae–Cathaya–Pinus), 4 (Cedrus, non-Cedrus Abietoideae, Larix–Pseudotsuga, and Piceae–Cathaya–Pinus), or 5 (Cedrus, non-Cedrus Abietoideae, Larix–Pseudotsuga, Picea, and Cathaya–Pinus) groups/subfamilies are more reasonable delimitations for Pinaceae. Specifically, our views on subfamilial classifications differ from previous studies in terms of the rank of Cedrus and with recognition of more than two subfamilies. PMID:20651328

Characterization of condensed tannins and carbohydrates in hot water bark extracts of European softwood species.

PubMed

Bianchi, Sauro; Kroslakova, Ivana; Janzon, Ron; Mayer, Ingo; Saake, Bodo; Pichelin, Frédéric

2015-12-01

Condensed tannins extracted from European softwood bark are recognized as alternatives to synthetic phenolics. The extraction is generally performed in hot water, leading to simultaneous extraction of other bark constituents such as carbohydrates, phenolic monomers and salts. Characterization of the extract's composition and identification of the extracted tannins' molecular structure are needed to better identify potential applications. Bark from Silver fir (Abies alba [Mill.]), European larch (Larix decidua [Mill.]), Norway spruce (Picea abies [Karst.]), Douglas fir (Pseudotsuga menziesii [Mirb.]) and Scots pine (Pinus sylvestris [L.]) were extracted in water at 60°C. The amounts of phenolic monomers, condensed tannins, carbohydrates, and inorganic compounds in the extract were determined. The molecular structures of condensed tannins and carbohydrates were also investigated (HPLC-UV combined with thiolysis, MALDI-TOF mass spectrometry, anion exchange chromatography). Distinct extract compositions and tannin structures were found in each of the analysed species. Procyanidins were the most ubiquitous tannins. The presence of phenolic glucosides in the tannin oligomers was suggested. Polysaccharides such as arabinans, arabinogalactans and glucans represented an important fraction of all extracts. Compared to traditionally used species (Mimosa and Quebracho) higher viscosities as well as faster chemical reactivities are expected in the analysed species. The most promising species for a bark tannin extraction was found to be larch, while the least encouraging results were detected in pine. A better knowledge of the interaction between the various extracted compounds is deemed an important matter for investigation in the context of industrial applications of such extracts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Limitation of the Cavitron technique by conifer pit aspiration.

PubMed

Beikircher, B; Ameglio, T; Cochard, H; Mayr, S

2010-07-01

The Cavitron technique facilitates time and material saving for vulnerability analysis. The use of rotors with small diameters leads to high water pressure gradients (DeltaP) across samples, which may cause pit aspiration in conifers. In this study, the effect of pit aspiration on Cavitron measurements was analysed and a modified 'conifer method' was tested which avoids critical (i.e. pit aspiration inducing) DeltaP. Four conifer species were used (Juniperus communis, Picea abies, Pinus sylvestris, and Larix decidua) for vulnerability analysis based on the standard Cavitron technique and the conifer method. In addition, DeltaP thresholds for pit aspiration were determined and water extraction curves were constructed. Vulnerability curves obtained with the standard method showed generally a less negative P for the induction of embolism than curves of the conifer method. Differences were species-specific with the smallest effects in Juniperus. Larix showed the most pronounced shifts in P(50) (pressure at 50% loss of conductivity) between the standard (-1.5 MPa) and the conifer (-3.5 MPa) methods. Pit aspiration occurred at the lowest DeltaP in Larix and at the highest in Juniperus. Accordingly, at a spinning velocity inducing P(50), DeltaP caused only a 4% loss of conductivity induced by pit aspiration in Juniperus, but about 60% in Larix. Water extraction curves were similar to vulnerability curves indicating that spinning itself did not affect pits. Conifer pit aspiration can have major influences on Cavitron measurements and lead to an overestimation of vulnerability thresholds when a small rotor is used. Thus, the conifer method presented here enables correct vulnerability analysis by avoiding artificial conductivity losses.

Role of EG-VEGF in human placentation: Physiological and pathological implications.

PubMed

Hoffmann, Pascale; Saoudi, Yasmina; Benharouga, Mohamed; Graham, Charles H; Schaal, Jean-Patrick; Mazouni, Chafika; Feige, Jean-Jacques; Alfaidy, Nadia

2009-08-01

Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.

European larch phenology in the Alps: can we grasp the role of ecological factors by combining field observations and inverse modelling?

NASA Astrophysics Data System (ADS)

Migliavacca, M.; Cremonese, E.; Colombo, R.; Busetto, L.; Galvagno, M.; Ganis, L.; Meroni, M.; Pari, E.; Rossini, M.; Siniscalco, C.; Morra di Cella, U.

2008-09-01

Vegetation phenology is strongly influenced by climatic factors. Climate changes may cause phenological variations, especially in the Alps which are considered to be extremely vulnerable to global warming. The main goal of our study is to analyze European larch ( Larix decidua Mill.) phenology in alpine environments and the role of the ecological factors involved, using an integrated approach based on accurate field observations and modelling techniques. We present 2 years of field-collected larch phenological data, obtained following a specifically designed observation protocol. We observed that both spring and autumn larch phenology is strongly influenced by altitude. We propose an approach for the optimization of a spring warming model (SW) and the growing season index model (GSI) consisting of a model inversion technique, based on simulated look-up tables (LUTs), that provides robust parameter estimates. The optimized models showed excellent agreement between modelled and observed data: the SW model predicts the beginning of the growing season (BGS) with a mean RMSE of 4 days, while GSI gives a prediction of the growing season length (LGS) with a RMSE of 5 days. Moreover, we showed that the original GSI parameters led to consistent errors, while the optimized ones significantly increased model accuracy. Finally, we used GSI to investigate interactions of ecological factors during springtime development and autumn senescence. We found that temperature is the most effective factor during spring recovery while photoperiod plays an important role during autumn senescence: photoperiod shows a contrasting effect with altitude decreasing its influence with increasing altitude.

European larch phenology in the Alps: can we grasp the role of ecological factors by combining field observations and inverse modelling?

PubMed

Migliavacca, M; Cremonese, E; Colombo, R; Busetto, L; Galvagno, M; Ganis, L; Meroni, M; Pari, E; Rossini, M; Siniscalco, C; Morra di Cella, U

2008-09-01

Vegetation phenology is strongly influenced by climatic factors. Climate changes may cause phenological variations, especially in the Alps which are considered to be extremely vulnerable to global warming. The main goal of our study is to analyze European larch (Larix decidua Mill.) phenology in alpine environments and the role of the ecological factors involved, using an integrated approach based on accurate field observations and modelling techniques. We present 2 years of field-collected larch phenological data, obtained following a specifically designed observation protocol. We observed that both spring and autumn larch phenology is strongly influenced by altitude. We propose an approach for the optimization of a spring warming model (SW) and the growing season index model (GSI) consisting of a model inversion technique, based on simulated look-up tables (LUTs), that provides robust parameter estimates. The optimized models showed excellent agreement between modelled and observed data: the SW model predicts the beginning of the growing season (B(GS)) with a mean RMSE of 4 days, while GSI gives a prediction of the growing season length (L(GS)) with a RMSE of 5 days. Moreover, we showed that the original GSI parameters led to consistent errors, while the optimized ones significantly increased model accuracy. Finally, we used GSI to investigate interactions of ecological factors during springtime development and autumn senescence. We found that temperature is the most effective factor during spring recovery while photoperiod plays an important role during autumn senescence: photoperiod shows a contrasting effect with altitude decreasing its influence with increasing altitude.

Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.

PubMed

Moll, Guido; Ignatowicz, Lech; Catar, Rusan; Luecht, Christian; Sadeghi, Behnam; Hamad, Osama; Jungebluth, Philipp; Dragun, Duska; Schmidtchen, Artur; Ringdén, Olle

2015-10-01

While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant.

PubMed

Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; Dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

2017-01-01

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant

PubMed Central

Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A.; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

2017-01-01

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV. PMID:29270171

Role of stress peptides during human pregnancy and labour.

PubMed

Hillhouse, Edward W; Grammatopoulos, Dimitris K

2002-09-01

Premature birth is the major source of perinatal death and disability. Furthermore, the intrauterine health of the baby is important for preventing certain adult diseases. However, the molecular mechanisms driving the onset of human labour remain uncertain, although several key players have been identified. It is becoming clear that there are many pathways to parturition in humans. Stress peptides, in particular placental corticotrophin releasing hormone (CRH) and possibly the related peptide urocortin, appear to play important roles throughout pregnancy. Plasma CRH is a predictor of the duration of human gestation. During most of pregnancy, CRH, acting via specific CRH receptor subtypes, plays a 'protective' role by promoting myometrial quiescence via the generation of cAMP and cGMP, and upregulation of nitric oxide synthase expression. At term, myometrial contractility is enhanced by a complex series of molecular switches, involving the upregulation of oxytocin receptor expression and crosstalk between the oxytocin and CRH receptors. This results in protein kinase C-induced phosphorylation of specific CRH receptor subtypes, with subsequent desensitization and a shift in the intracellular microenvironment to enhance contractility. CRH/urocortin, via specific receptor isoforms, is now able to activate Gq and potentially enhance the oxytocin-driven generation of inositol triphosphate. In addition, CRH/urocortin, via specific CRH receptor subtypes, may generate prostaglandins from the fetal membranes and decidua, play a role in placental vasodilatation and participate in fetal adrenal function and organ maturation. These peptides and receptors are phylogenetically ancient and well preserved across species. They may have evolved as a mechanism to protect against the 'stress' of premature birth.

Carbon and oxygen isotope signatures in conifers from the Swiss National Park

NASA Astrophysics Data System (ADS)

Churakova (Sidorova), Olga; Saurer, Matthias; Siegwolf, Rolf; Bryukhanova, Marina; Bigler, Christof

2015-04-01

Our study investigates the physiological response and plasticity of trees under climatic changes for larch (Larix decidua) and mountain pine (Pinus mugo var. uncinata) in the Swiss National Park.This research was done in the context of investigation tree mortality and their potential to survive under the harsh mountainous conditions. For the stable isotope analysis we selected four mountain pine and four larch trees from each a south- and north-facing slope. Oxygen isotope ratios can give insight into water sources and evaporative processes. To understand the differential response of mountain pine and larch to short-term climatic changes we measured 18O/16O in water extracted from twigs and needles as well as soil samples for each species at both sites. The seasonal variabilities in 18O/16O needles and twigs of mountain pine and larch trees as well as soil samples were related to changes in climate conditions from end of May until middle of October. To reveal the main climatic factors driving tree growth of pine and larch trees in the long-term, tree-ring width chronologies were built and bulk 18O/16O, 13C/12C wood chronologies were analyzed and correlated with climatic parameters over the last 100 years. The results indicate a strong influence of spring and summer temperatures for larch trees, while variation of spring and summer precipitations is more relevant for mountain pine trees. This work is supported by the Swiss National Science Foundation, Marie-Heim Vögtlin Program PMPDP-2 145507

IFPA Award in Placentology lecture: molecular regulation of human trophoblast invasion.

PubMed

Knöfler, M; Pollheimer, J

2012-02-01

Invasion of extravillous trophoblast cell types into maternal uterine tissues is essential for successful human placental development and progression of pregnancy. Whereas endovascular trophoblasts migrate into the maternal spiral arteries, interstitial trophoblasts invade the decidual stroma, colonize the vessels from outside and communicate with diverse uterine cell types such as decidual stromal cells, macrophages and uterine NK cells. For example, interstitial trophoblasts expressing polymorphic human leukocyte antigen-C interact with uterine NK cells through binding to their killer immunoglobulin-like receptors which likely plays a role in trophoblast invasion and reproductive success of pregnancy. Both extravillous trophoblast subtypes are critically involved in the vascular transformation of the spiral arteries into dilated conduits ensuring appropriate blood flow into the intervillous space. Failures in this remodeling process are thought to be associated with severe forms of fetal growth restriction, preeclampsia and other pregnancy complications warranting studies on the molecular regulation of extravillous trophoblast differentiation. Moreover, interstitial trophoblast-derived hormones may regulate diverse biological functions in the decidua. In particular, human chorionic gonadotrophin has been shown to promote angiogenesis and to suppress apoptosis of endometrial stromal cells. In return, decidual cells produce a plethora of soluble factors controlling trophoblast invasion in a time- and distance-dependent manner. However, the underlying mechanisms have not been fully elucidated. Here, we will summarize autocrine as well as paracrine factors regulating invasion of extravillous trophoblasts and discuss critical signaling cascades involved. In addition, we will focus on key regulatory transcription factors controlling cell column proliferation and differentiation of the human extravillous trophoblast. Copyright © 2012 Elsevier Ltd. All rights reserved.

nm23 regulates decidualization through the PI3K-Akt-mTOR signaling pathways in mice and humans.

PubMed

Zhang, Xue; Fu, Li-Juan; Liu, Xue-Qing; Hu, Zhuo-Ying; Jiang, Yu; Gao, Ru-Fei; Feng, Qian; Lan, Xi; Geng, Yan-Qing; Chen, Xue-Mei; He, Jun-Lin; Wang, Ying-Xiong; Ding, Yu-Bin

2016-10-01

Does nm23 have functional significance in decidualization in mice and humans? nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs. The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation. We first analyzed the expression profile of nm23 in mice during early pregnancy (n = 6/group), pseudopregnancy (n = 6/group) and artificial decidualization (n = 6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways. We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot. NM23-M1 was specifically expressed in the decidual zone during early pregnancy and in artificially induced deciduoma, and NM23-H1 was strongly expressed in human first trimester decidua. The expression of nm23 was upregulated by oestradiol and progesterone (P < 0.05 versus control) in vitro in mESCs and T-HESC, and this was inhibited by their respective receptor antagonists, ICI 182,780 and RU486. Mouse and human nm23 knockdown decreased ESC proliferation and differentiation (P < 0.05 versus control). The PI3K-Akt-mTOR signaling pathways were downstream mediators of nm23 in mESCs and T-HESCs decidualization. Whether the nm23 regulates decidualization via the activation of AMPK, RAS, PKA, STAT3 or other signaling molecules remains to be determined. The role of nm23 in decidualization was tested in vitro only. Results demonstrate that nm23 plays a vital role in decidualization in mice and humans and that nm23 gene expression is hormonally regulated. The downregulation of nm23 in decidua during the first trimester may be associated with infertility in women. This study was supported by the National Natural Science Foundation of China (grant nos. 81370731, 31571551 and 31571190), the Science and Technology Project of Chongqing Education Committee (KJ130309), open funding by the Chongqing Institute for Family Planning (1201) and the Excellent Young Scholars of Chongqing Medical University (CQYQ201302). The authors have no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparative Chloroplast Genomes of Pinaceae: Insights into the Mechanism of Diversified Genomic Organizations

PubMed Central

Wu, Chung-Shien; Lin, Ching-Ping; Hsu, Chi-Yao; Wang, Rui-Jiang; Chaw, Shu-Miaw

2011-01-01

Abstract Pinaceae, the largest family of conifers, has diversified organizations of chloroplast genomes (cpDNAs) with the two typical inverted repeats (IRs) highly reduced. To unravel the mechanism of this genomic diversification, we examined the cpDNA organizations from 53 species of the ten Pinaceous genera, including those of Larix decidua (122,474 bp), Picea morrisonicola (124,168 bp), and Pseudotsuga wilsoniana (122,513 bp), which were firstly elucidated. The results uncovered four distinct cpDNA forms (A−C and P) that are due to rearrangements of two ∼20 and ∼21 kb specific fragments. The C form was documented for the first time and the A form might be the most ancestral one. In addition, only the individuals of Ps. macrocarpa and Ps. wilsoniana were detected to have isomeric cpDNA forms. Three types (types 1−3) of Pinaceae-specific repeats situated nearby the rearranged fragments were found to be syntenic. We hypothesize that type 1 (949 ± 343 bp) and type 3 (608 ± 73 bp) repeats are substrates for homologous recombination (HR), whereas type 2 repeats are likely inactive for HR because of their relatively short sizes (151 ± 30 bp). Conversions among the four distinct forms may be achieved by HR and mediated by type 1 or 3 repeats, thus resulting in increased diversity of cpDNA organizations. We propose that in the Pinaceae cpDNAs, the reduced IRs have lost HR activity, then decreasing the diversity of cpDNA organizations, but the specific repeats that the evolution endowed Pinaceae complement the reduced IRs and increase the diversity of cpDNA organizations. PMID:21402866

E-Spun Composite Fibers of Collagen and Dragline Silk Protein: Fiber Mechanics, Biocompatibility, and Application in Stem Cell Differentiation

PubMed Central

2015-01-01

Biocomposite matrices with high mechanical strength, high stability, and the ability to direct matrix-specific stem cell differentiation are essential for the reconstruction of lesioned tissues in tissue engineering and cell therapeutics. Toward this end, we used the electrospinning technique to fabricate well-aligned composite fibers from collagen and spider dragline silk protein, obtained from the milk of transgenic goats, mimicking the native extracellular matrix (ECM) on a similar scale. Collagen and the dragline silk proteins were found to mix homogeneously at all ratios in the electrospun (E-spun) fibers. As a result, the ultimate tensile strength and elasticity of the fibers increased monotonically with silk percentage, whereas the stretchability was slightly reduced. Strikingly, we found that the incorporation of silk proteins to collagen dramatically increased the matrix stability against excessive fiber swelling and shape deformation in cell culture medium. When human decidua parietalis placental stem cells (hdpPSCs) were seeded on the collagen–silk matrices, the matrices were found to support cell proliferation at a similar rate as that of the pure collagen matrix, but they provided cell adhesion with reduced strengths and induced cell polarization at varied levels. Matrices containing 15 and 30 wt % silk in collagen (CS15, CS30) were found to induce a level of neural differentiation comparable to that of pure collagen. In particular, CS15 matrix induced the highest extent of cell polarization and promoted the development of extended 1D neural filaments strictly in-line with the aligned fibers. Taking the increased mechanical strength and fiber stability into consideration, CS15 and CS30 E-spun fibers offer better alternatives to pure collagen fibers as scaffolds that can be potentially utilized in neural tissue repair and the development of future nanobiodevices. PMID:25405355

Root reinforcement and its implications in shallow landsliding susceptibility on a small alpine catchment

NASA Astrophysics Data System (ADS)

Morandi, M. C.; Farabegoli, E.; Onorevoli, G.

2012-04-01

Roots shear resistance offers a considerable contribution to hill-slope stability on vegetated terrains. Through the pseudo-cohesion of shrubs, trees and turf's roots, the geomechanical properties of soils can be drastically increased, exerting a positive influence on the hillslope stability. We analysed the shallow landsliding susceptibility of a small alpine catchment (Duron valley, Central Dolomites, Italy) that we consider representative of a wide altitude belt of the Dolomites (1800 - 2400 m a.s.l). The catchment is mostly mantled by grass (Nardetum strictae s.l.), with clustered shrubs (Rhododendron hirsutum and Juniperus nana), and trees (Pinus cembra, Larix decidua and Picea abies). The soil depth, investigated with direct and indirect methods, ranges from 0 to 180 cm, with its peak at the hollow axes. Locally, the bedrock, made of Triassic volcanic rocks, is deeply incised by the Holocene drainage network. Intensive grazing of cows and horses pervades the catchment area and cattle-trails occupy ca 20% of the grass cover. We used laboratory and field tests to characterize the geotechnical properties of these alpine soils; moreover we designed and tested an experimental device that measures, in situ, the shear strengths of the grass mantle. In the study area we mapped 18 shallow landslides, mostly related to road cuts and periodically reactivated as retrogressive landslides. The triggering mechanisms of these shallow landslides were qualitatively analysed at large scale and modelled at smaller scale. We used SHALSTAB to model the shallow landsliding susceptibility of the catchment at the basin scale and SLIDE (RocScience) to compute the Safety Factor at the versant scale. Qualitative management solutions are provided, in order to reduce the shallow landsliding susceptibility risk in this alpine context.

Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model1

PubMed Central

Thompson, Loren P.; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P.

2016-01-01

Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39–40 days) or term (60–65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction. PMID:27806942

Climate change at upper treeline: How do trees on the edge react to increasing temperatures?

NASA Astrophysics Data System (ADS)

Jochner, Matthias; Bugmann, Harald; Nötzli, Magdalena; Bigler, Christof

2017-04-01

Treeline ecotones are thought to be particularly sensitive to climate warming, and an alteration of their growth conditions may have important implications for the ecosystem services they supply in mountain regions. We use a novel approach to quantify effects of a changing climate on tree growth, using case studies in the European Alps. We compiled tree-ring data from almost 600 trees of four species at treeline in three climate regions of Switzerland. Temperature loggers installed along transects provided data for a precise interpolation of temperatures experienced by the sampled trees. To assess the influence of temperature on annual growth, we used linear mixed-effects models, allowing us to quantify effect sizes and to account for between-tree growth variability. After removing biological growth trends, we isolated temporal trends of ring-width indices. Furthermore, we fitted non-linear regression models to radial growth rates of individual years with temperature and tree age as predicting covariates for a fine-scale investigation of the temperature dependency of tree growth. For all species, climate-growth linear mixed-effects models indicated strong positive responses of ring-width indices to temperature in early summer and previous year's autumn, featuring considerable between-tree variability. All species showed positive ring-width index trends at treeline but different interactions with elevation: Larix decidua exhibited a declining ring-width index trend with decreasing elevation, whereas Picea abies, Pinus cembra and Pinus mugo showed increasing and/or stable trends. Not only reflected our findings the effects of ameliorated growth conditions, they might have also revealed suspected negative and positive feedbacks of climate change on growth, and increased the knowledge about the functional form and parameterization of the temperature dependency of tree growth.

Altered glucose transport to utero-embryonic unit in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

PubMed

Arnab, Banerjee; Amitabh, Krishna

2011-02-10

The aim of this study was to compare the changes in concentration of glucose and glucose transporters (GLUTs) in the utero-embryonic unit, consisting of decidua, trophoblast and embryo, during delayed and non-delayed periods to understand the possible cause of delayed embryonic development in Cynopterus sphinx. The results showed a significantly decreased concentration of glucose in the utero-embryonic unit due to decline in the expression of insulin receptor (IR) and GLUT 3, 4 and 8 proteins in the utero-embryonic unit during delayed period. The in vitro study showed suppressive effect of insulin on expression of GLUTs 4 and 8 in the utero-embryonic unit and a significant positive correlation between the decreased amount of glucose consumed by the utero-embryonic unit and decreased expression of GLUTs 4 (r=0.99; p<0.05) and 8 (r=0.98; p<0.05). The in vivo study showed expression of IR and GLUT 4 proteins in adipose tissue during November suggesting increased transport of glucose to adipose tissue for adipogenesis. This study showed increased expression of HSL and OCTN2 and increased availability of l-carnitine to utero-embryonic unit suggesting increased transport of fatty acid to utero-embryonic unit during the period of delayed embryonic development. Hence it appears that due to increased transport of glucose for adipogenesis prior to winter, glucose utilization by utero-embryonic unit declines and this may be responsible for delayed embryonic development in C. sphinx. Increased supply of fatty acid to the delayed embryo may be responsible for its survival under low glucose condition but unable to promote embryonic development in C. sphinx. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Expression of two isoforms of CD44 in human endometrium.

PubMed

Behzad, F; Seif, M W; Campbell, S; Aplin, J D

1994-10-01

The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.

Role of inflammatory proteins S100A8 and S100A9 in pathophysiology of recurrent early pregnancy loss.

PubMed

Nair, R R; Khanna, A; Singh, K

2013-09-01

Altered expression of inflammatory molecule at the maternal fetal interface is associated with early pregnancy loss. S100A8 and S100A9 are inflammatory proteins and they exhibit cytokine like function enhancing leukocyte recruitment to the inflammatory site. Reports from mouse model suggest the role of S100A8 with the vasculature of the decidual tissue and leukocyte recruitment during early pregnancy. Hence we hypothesized that maternal overexpression of S100A8 & S100A9 might increase the recruitment of inflammatory leukocytes in maternal-fetal interface resulting in uteroplacental perfusion deficiency, development of thrombotic events, and placental hypoxia, eventually embryo abortion. In the present study we investigated altered expression of S100A8 and S100A9 in 25 recurrent early pregnancy loss (REPL) patients compared to 40 induced abortion subjects as controls. S100A8 and S100A9 mRNA were evaluated using semi-quantitative RT-PCR and quantitative real-time PCR. To determine if differential expression pattern of these transcripts is translated to protein western blot analysis was performed.S100A8 and S100A9 mRNA and protein level were significantly increased in endometrial decidua tissue (p < 0.05) of REPL patients as compared to controls. This is the first report predicting the role of inflammatory molecules S100A8 & S100A9 in REPL. It opens a new perspective for understanding significance of S100A8 and S100A9 in pregnancy maintenance and outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

Integrating proximal and satellite optical data for the analysis of ecosystem carbon uptake and plant phenology at the European larch Specnet site

NASA Astrophysics Data System (ADS)

Galvagno, Marta; Gamon, John; Cremonese, Edoardo; Garrity, Steven; Huemmrich, K. Fred; Filippa, Gianluca; Morra di Cella, Umberto; Rossini, Micol

2017-04-01

Automated canopy-level optical sampling in tandem with ecosystem-atmosphere flux observations is continuously carried on at a variety of ecosystems through the Specnet network (http://specnet.info/). Specifically, 9 sites within US and Europe were selected since 2015, to investigate the use of novel NDVI and PRI low-cost sensors for the analysis of ecosystem functioning and phenology. Different plant functional types, such as grasslands, deciduous, and evergreen forests belong to the network, here we present specific data from the larch (Larix decidua Mill.) forest Italian site. Three automated NDVI and three automated PRI spectral reflectance sensors (Decagon Devices Inc.) were installed in 2015 on the top of the 20-meters eddy covariance tower, pointing toward the west, north, and east orientations. An additional system, composed by one NDVI and PRI system was installed to monitor the understory component. The objective of this analysis is the comparison between these in-situ inexpensive sensors, independent NDVI and PRI sensors (Skye Instruments) previously installed on the 20-meters tower and satellite-derived NDVI. Both MODIS and Sentinel NDVI data were used for the comparison. Moreover, the newly derived chlorophyll/carotenoid index (CCI, Gamon et al. 2016), computed as the normalized difference between the NDVI red band and PRI 532 nm band, was tested to estimate the seasonal pattern of daily Gross Primary Productivity (GPP) of the larch forest. Results showed that the seasonality of NDVI was comparable among in-situ sensors and satellite data, though orientation-specific differences were observed. Both NDVI and CCI tracked daily GPP, but with different sensitivity to its seasonality. Future analysis will be directed toward a comparison between this site-based results with the other sites within the Specnet network.

Placenta Defects and Embryonic Lethality Resulting from Disruption of Mouse Hydroxysteroid (17-β) Dehydrogenase 2 Gene

PubMed Central

Rantakari, Pia; Strauss, Leena; Kiviranta, Riku; Lagerbohm, Heidi; Paviala, Jenni; Holopainen, Irma; Vainio, Seppo; Pakarinen, Pirjo; Poutanen, Matti

2008-01-01

Hydroxysteroid (17-β) dehydrogenase 2 (HSD17B2) is a member of aldo-keto reductase superfamily, known to catalyze the inactivation of 17β-hydroxysteroids to less active 17-keto forms and catalyze the conversion of 20α-hydroxyprogesterone to progesterone in vitro. To examine the role of HSD17B2 in vivo, we generated mice deficient in Hsd17b2 [HSD17B2 knockout (KO)] by a targeted gene disruption in embryonic stem cells. From the homozygous mice carrying the disrupted Hsd17b2, 70% showed embryonic lethality appearing at the age of embryonic d 11.5 onward. The embryonic lethality was associated with reduced placental size measured at embryonic d 17.5. The HSD17B2KO mice placentas presented with structural abnormalities in all three major layers: the decidua, spongiotrophoblast, and labyrinth. Most notable was the disruption of the spongiotrophoblast and labyrinthine layers, together with liquid-filled cysts in the junctional region and the basal layer. Treatments with an antiestrogen or progesterone did not rescue the embryonic lethality or the placenta defect in the homozygous mice. In hybrid background used, 24% of HSD17B2KO mice survived through the fetal period but were born growth retarded and displayed a phenotype in the brain with enlargement of ventricles, abnormal laminar organization, and increased cellular density in the cortex. Furthermore, the HSD17B2KO mice had unilateral renal degeneration, the affected kidney frequently appearing as a fluid-filled sac. Our results provide evidence for a role for HSD17B2 enzyme in the cellular organization of the mouse placenta. PMID:18048640

Genetic variation, phenotypic stability, and repeatability of drought response in European larch throughout 50 years in a common garden experiment

PubMed Central

George, Jan-Peter; Grabner, Michael; Karanitsch-Ackerl, Sandra; Mayer, Konrad; Weißenbacher, Lambert; Schueler, Silvio

2017-01-01

Abstract Assessing intra-specific variation in drought stress response is required to mitigate the consequences of climate change on forest ecosystems. Previous studies suggest that European larch (Larix decidua Mill.), an important European conifer in mountainous and alpine forests, is highly vulnerable to drought. In light of this, we estimated the genetic variation in drought sensitivity and its degree of genetic determination in a 50-year-old common garden experiment in the drought-prone northeastern Austria. Tree ring data from larch provenances originating from across the species' natural range were used to estimate the drought reaction in four consecutive drought events (1977, 1981, 1990–1994, and 2003) with extremely low standardized precipitation- and evapotranspiration-index values that affected growth in all provenances. We found significant differences among provenances across the four drought periods for the trees’ capacity to withstand drought (resistance) and for their capacity to reach pre-drought growth levels after drought (resilience). Provenances from the species' northern distribution limit in the Polish lowlands were found to be more drought resistant and showed higher stability across all drought periods than provenances from mountainous habitats at the southern fringe. The degree of genetic determination, as estimated by the repeatability, ranged up to 0.39, but significantly differed among provenances, indicating varying degrees of natural selection at the provenance origin. Generally, the relationship between the provenances’ source climate and drought behavior was weak, suggesting that the contrasting patterns of drought response are a result of both genetic divergence out of different refugial lineages and local adaptation to summer or winter drought conditions. Our analysis suggests that European larch posseses high genetic variation among and within provenances that can be used for assisted migration and breeding programs. PMID:28173601

Release and retention patterns of organic compounds and nutrients after the cold period in foliar litterfall of pure European larch, common beech and red oak plantations in Lithuania

NASA Astrophysics Data System (ADS)

Čiuldienė, D.; Aleinikovienė, J.; Muraškienė, M.; Marozas, V.; Armolaitis, K.

2017-01-01

This study was carried out in alien warmth-tolerant forest plantations of red oak ( Quercus rubra), common beech ( Fagus sylvatica) and European larch ( Larix decidua). We compared the changes in foliar litterfall mass and biochemical composition after five months of cold period. The mean mass of fresh foliar litterfall collected in late autumn was 30% higher in red oak compared to the larch and beech plantations. After the cold period, the reduction of foliar litterfall mass did not exceed 10% in any of the studied plantations. The fresh foliar litterfall of red oak was the richest in cellular fibre and easily decomposable glucose and nutrients such as P and Mg, larch was distinguished by the highest lignin, N, K and Ca concentrations, while beech fresh foliar litterfall was the poorest in the aforementioned nutrients. After the cold period, the changes in the biochemical composition of foliar litterfall revealed different patterns. In the spring, the beech and red oak foliar litterfall was the richest in N, P and Ca, meanwhile the larch foliar litterfall still had the highest concentration of lignin but, in contrast to the autumn, was the poorest in nutrients. After the cold period Lignin: N, C: N and C: P ratios reached critical values indicating that the foliar litterfall of beech and red oak had started to decompose. The highest lignin concentration and the highest and most stable Lignin: N, C: N, C: P and N: P ratios after the cold period indicated that the slowest foliar litterfall decomposition took place in the larch plantation.

Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion

PubMed Central

Kusuma, Gina D.; Brennecke, Shaun P.; O’Connor, Andrea J.; Kalionis, Bill

2017-01-01

Mesenchymal stem/stromal cells (MSCs) exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM) prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower) to produce the dECM drastically limits the utility and impact of this technology. Here, we report that primary MSCs expanded on dECM prepared from high passage number (passage 25) human telomerase reverse transcriptase (hTERT) transduced immortal MSC cell lines also exhibit increased proliferation and osteogenic differentiation. Two hTERT-transduced placenta-derived MSC cell lines, CMSC29 and DMSC23 [derived from placental chorionic villi (CMSCs) and decidua basalis (DMSCs), respectively], were used to prepare dECM-coated substrates. These dECM substrates showed structural and biochemical differences. Primary DMSCs cultured on dECM-DMSC23 showed a three-fold increase in cell number after 14 days expansion in culture and increased osteogenic differentiation compared with controls. Primary CMSCs cultured on the dECM-DMSC23 exhibited a two-fold increase in cell number and increased osteogenic differentiation. We conclude that immortal MSC cell lines derived from different parts of the placenta produce dECM with varying abilities for supporting increased primary MSC expansion while maintaining important primary MSC properties. Additionally, this is the first demonstration of using high passage number cells to produce dECM that can promote primary MSC expansion, and this advancement greatly increases the feasibility and applicability of dECM-based technologies. PMID:28152107

Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

PubMed

Carter, Anthony M

2011-04-01

Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions

PubMed Central

Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y.

2016-01-01

On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia. In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. PMID:27402618

Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions.

PubMed

Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y

2016-01-01

On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

An alpine treeline in a carbon dioxide-rich world: synthesis of a nine-year free-air carbon dioxide enrichment study.

PubMed

Dawes, Melissa A; Hagedorn, Frank; Handa, Ira Tanya; Streit, Kathrin; Ekblad, Alf; Rixen, Christian; Körner, Christian; Hättenschwiler, Stephan

2013-03-01

We evaluated the impacts of elevated CO2 in a treeline ecosystem in the Swiss Alps in a 9-year free-air CO2 enrichment (FACE) study. We present new data and synthesize plant and soil results from the entire experimental period. Light-saturated photosynthesis (A max) of ca. 35-year-old Larix decidua and Pinus uncinata was stimulated by elevated CO2 throughout the experiment. Slight down-regulation of photosynthesis in Pinus was consistent with starch accumulation in needle tissue. Above-ground growth responses differed between tree species, with a 33 % mean annual stimulation in Larix but no response in Pinus. Species-specific CO2 responses also occurred for abundant dwarf shrub species in the understorey, where Vaccinium myrtillus showed a sustained shoot growth enhancement (+11 %) that was not apparent for Vaccinium gaultherioides or Empetrum hermaphroditum. Below ground, CO2 enrichment did not stimulate fine root or mycorrhizal mycelium growth, but increased CO2 effluxes from the soil (+24 %) indicated that enhanced C assimilation was partially offset by greater respiratory losses. The dissolved organic C (DOC) concentration in soil solutions was consistently higher under elevated CO2 (+14 %), suggesting accelerated soil organic matter turnover. CO2 enrichment hardly affected the C-N balance in plants and soil, with unaltered soil total or mineral N concentrations and little impact on plant leaf N concentration or the stable N isotope ratio. Sustained differences in plant species growth responses suggest future shifts in species composition with atmospheric change. Consistently increased C fixation, soil respiration and DOC production over 9 years of CO2 enrichment provide clear evidence for accelerated C cycling with no apparent consequences on the N cycle in this treeline ecosystem.

Alkaline phosphatases contribute to uterine receptivity, implantation, decidualization and defense against bacterial endotoxin in hamsters

PubMed Central

Lei, Wei; Nguyen, Heidi; Brown, Naoko; Ni, Hua; Kiffer-Moreira, Tina; Reese, Jeff; Millán, José Luis; Paria, Bibhash C.

2013-01-01

Alkaline phosphatase (AP) activity has been demonstrated in the uterus of several species, but its importance in the uterus, in general and during pregnancy, is yet to be revealed. In this study, we focused on identifying AP isozyme types, and their hormonal regulation, cell-type and event-specific expression and possible functions in the hamster uterus during the cycle and early pregnancy. Our RT-PCR and in situ hybridization studies demonstrated that among the known Akp2, Akp3, Akp5 and Akp6 murine AP isozyme genes, hamster uteri express only Akp2 and Akp6; and both genes are co-expressed in luminal epithelial cells. Studies in cyclic and ovariectomized hamsters established that while progesterone is the major uterine Akp2 inducer, both progesterone and estrogen are strong Akp6 regulators. Studies in preimplantation uteri showed induction of both genes and the activity of their encoded isozymes in luminal epithelial cells during uterine receptivity. However, at the beginning of implantation, Akp2 showed reduced expression in luminal epithelial cells surrounding the implanted embryo. In contrast, expression of Akp6 and its isozyme was maintained in luminal epithelial cells adjacent to, but not away from, the implanted embryo. Following implantation, stromal transformation to decidua was associated with induced expressions of only Akp2 and its isozyme. We next demonstrated that uterine APs dephosphorylate and detoxify endotoxin lipopolysaccharide at their sites of production and activity. Taken together, our findings suggest that uterine APs contribute to uterine receptivity, implantation, and decidualization in addition to their role in protection of the uterus and pregnancy against bacterial infection. PMID:23929901

Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

PubMed Central

Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

2016-01-01

Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

Differences in regulatory T-cell and dendritic cell pattern in decidual tissue of placenta accreta/increta cases.

PubMed

Schwede, S; Alfer, J; von Rango, U

2014-06-01

Primary infertility, miscarriage, and preeclampsia have been correlated with reduced numbers of regulatory T-cells (Treg) suggesting that decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT tolerance. In contrast increased numbers of Treg-cells may be responsible for over-invasion of EVT. As the maturation status of dendritic cells (DC) influences T-cell behavior (tolerance or immune activation), altered relation between immature and mature DCs may also influence EVT invasion. Paraffin-embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single-stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the leukocyte subpopulations was performed for decidua parietalis and basalis as characterized by cytokeratin-positive EVT. Statistical analysis was performed by using the Mann-Whitney test. There were significantly fewer CD4(+) cells in Pc than in IUG. Concerning the Treg-markers, FoxP3(+) cells are significantly increased. CD25(+) cells showed a small non-significant increase in Pc in comparison to IUG. Concerning dendritic cells, immature non-activated CD209(+) DCs were significantly decreased in Pc while immature activated CD205(+) DCs were slightly but non-significantly increased. Mature activated CD83(+) DC were non-significantly decreased in IUG vs Pc. The increased number of Treg-cells in Pc suggests significance for these cells in the regulation of trophoblast invasion. Their adequate interaction with other lymphocyte populations (e.g. adequately maturated dendritic cells) may be one mechanism to assure controlled EVT invasion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Placenta accreta is associated with decreased decidual natural killer (dNK) cells population: a comparative pilot study.

PubMed

Laban, Mohamed; Ibrahim, Eman Abdel-Salam; Elsafty, Mohammed Saeed Eldin; Hassanin, Alaa Sayed

2014-10-01

Placenta accreta is a general term describes abnormal adherent placenta to the uterine wall. When the chorionic villi invade the myometrium, the term placenta increta is appropriate. Nowadays, it is one of the increasing causes of materno-fetal morbidities and mortality. The aim of this research was to evaluate density of decidual natural killer cells (dNK, CD56+(bright)) in decidua basalis in patients with placenta accreta. We recruited 76 patients from Ain Shams Maternity Hospital between June 2012 to August 2013, they were divided into study subgroup (A) which included 10 patients who underwent cesarean hysterectomy due to unseparated placenta accreta, study subgroup (B) included 16 patients with separated placenta accreta, a comparison group included 25 patients with placenta previa and a control group included 25 patients with normally situated placenta. All patients underwent elective cesarean delivery. Decidual biopsies were taken during the operation. An immunohistochemical staining for (dNK, CD56+(bright)) and a semi quantitative scoring were done. One-way ANOVA and Fisher Exact tests were used for statistical correlation. The mean dNK cells scores were (0.4±0.5, 1.9±1, 3.3±0.5 and 3.5±0.5) for study subgroups (A), (B) comparison and control groups respectively) with a highly significant statistical difference (P<0.001). There was a significant statistical difference between study subgroups (A) and (B) P=0.002 .There was an insignificant statistical correlation between dNK scores and number of previous uterine scars (P=0.46). These findings suggest that low dNK score was associated with cases of morbidly adherent placenta accreta. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus ater, with observations on intermediate filament proteins in the decidua and intraplacental trophoblast.

PubMed

Badwaik, N K; Rasweiler, J J; Muradali, F

1998-11-01

Histological and immunocytochemical studies of gravid reproductive tracts obtained from the white-winged vampire bat (Diaemus youngi) and the black mastiff bat (Molossus ater) have established that both species develop unusually invasive trophoblast. This is released by the developing discoidal haemochorial placenta, expresses both cytokeratins and vimentin, and invades the myometrium and adjacent tissues (including the ovaries) via interstitial migration within the walls of maternal blood vessels. Hence, this trophoblast is noteworthy for the extent to which it undergoes an epithelial-mesenchymal transformation. In Molossus, it originates from the cytotrophoblastic shell running along the base of the placenta, is mononuclear, and preferentially invades maternal arterial vessels serving the discoidal placenta. This trophoblast may have a role in dilatation of these vessels when the discoidal placenta becomes functional. In Diaemus, the highly invasive trophoblast appears to originate instead from a layer of syncytiotrophoblast on the periphery of the placenta is multinucleated, and vigorously invades both arterial and venous vessels. During late pregnancy, it becomes extensively branched and sends attenuated processes around many of the myometrial smooth muscle fibres. In view of its distribution, this trophoblast could have important influences upon myometrial contractility and the function of blood vessels serving the gravid tract. Other aspects of intermediate filament expression in the uteri and placentae of these bats are also noteworthy. Many of the decidual giant cells in Molossus co-express cytokeratins and vimentin, while the syncytiotrophoblast lining the placental labyrinth in Diaemus late in pregnancy expresses little cytokeratin.

Warm season precipitation signal in δ2 H values of wood lignin methoxyl groups from high elevation larch trees in Switzerland.

PubMed

Riechelmann, Dana F C; Greule, Markus; Siegwolf, Rolf T W; Anhäuser, Tobias; Esper, Jan; Keppler, Frank

2017-10-15

In this study, we tested stable hydrogen isotope ratios of wood lignin methoxyl groups (δ 2 H methoxyl values) as a palaeoclimate proxy in dendrochronology. This is a quite new method in the field of dendrochronology and the sample preparation is much simpler than the methods used before to measure δ 2 H values from wood. We measured δ 2 H methoxyl values in high elevation larch trees (Larix decidua Mill.) from Simplon Valley (southern Switzerland). Thirty-seven larch trees were sampled and five individuals analysed for their δ 2 H methoxyl values at annual (1971-2009) and pentadal resolution (1746-2009). The δ 2 H methoxyl values were measured as CH 3 I released upon treatment of the dried wood samples with hydroiodic acid. 10-90 μL from the head-space were injected into the gas chromatography/high-temperature conversion/isotope ratio mass spectrometry (GC/HTC-IRMS) system. Testing the climate response of the δ 2 H methoxyl values, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation. The pentadally resolved δ 2 H methoxyl series do not show any significant correlation to climate parameters. Increased precipitation during June and July, which are on average warm and relatively dry months, results in higher δ 2 H values of the xylem water and, therefore, higher δ 2 H values in the lignin methoxyl groups. Therefore, we suggest that δ 2 H methoxyl values of high elevation larch trees might serve as a summer precipitation proxy. Copyright © 2017 John Wiley & Sons, Ltd.

Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion.

PubMed

Kusuma, Gina D; Brennecke, Shaun P; O'Connor, Andrea J; Kalionis, Bill; Heath, Daniel E

2017-01-01

Mesenchymal stem/stromal cells (MSCs) exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM) prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower) to produce the dECM drastically limits the utility and impact of this technology. Here, we report that primary MSCs expanded on dECM prepared from high passage number (passage 25) human telomerase reverse transcriptase (hTERT) transduced immortal MSC cell lines also exhibit increased proliferation and osteogenic differentiation. Two hTERT-transduced placenta-derived MSC cell lines, CMSC29 and DMSC23 [derived from placental chorionic villi (CMSCs) and decidua basalis (DMSCs), respectively], were used to prepare dECM-coated substrates. These dECM substrates showed structural and biochemical differences. Primary DMSCs cultured on dECM-DMSC23 showed a three-fold increase in cell number after 14 days expansion in culture and increased osteogenic differentiation compared with controls. Primary CMSCs cultured on the dECM-DMSC23 exhibited a two-fold increase in cell number and increased osteogenic differentiation. We conclude that immortal MSC cell lines derived from different parts of the placenta produce dECM with varying abilities for supporting increased primary MSC expansion while maintaining important primary MSC properties. Additionally, this is the first demonstration of using high passage number cells to produce dECM that can promote primary MSC expansion, and this advancement greatly increases the feasibility and applicability of dECM-based technologies.

Serum ischemia modified albumin level and its relationship with the thiol/disulfide balance in placenta percreta patients.

PubMed

Uyanikoglu, Hacer; Sak, Muhammet Erdal; Tatli, Faik; Hilali, Nese Gul; Sak, Sibel; Incebiyik, Adnan; Barut, Mert Ulas; Erel, Ozcan; Gonel, Ataman

2018-06-08

The pathogenesis of placenta percreta (PP) is not very well known. This study was designed to analyse the oxidative stress (OS), the thiol/disulphide balance, and ischaemia-modified albumin (IMA) the women with PP. The study included 38 pregnant women with PP and 40 similarly aged healthy pregnant women in their third trimester of gestation. We measured the IMA, native and total thiols, and disulphide concentrations in the maternal sera of all of the participating women. The IMA levels were higher and the native and total thiols were lower in the PP group than in the control group. However, there was no statistical significance with respect to the thiol/disulphide balance between the two groups. The results of this study suggest that an increase in the ischaemia and OS and a decrease in the antioxidant status may contribute to the pathogenesis of PP. Impact statement What is already known on this subject? Placenta percreta (PP) is a serious complication of pregnancy. Although there are several studies investigating the pathophysiological mechanism of PP, whether the pathology results from a lack of decidua or from the over-invasiveness of trophoblasts remains controversial. The pathology of PP is poorly understood. What do the results of this study add? This prospective study has shown an increased ischaemia modified albumin (IMA) and a decreased antioxidant capacity in the patients with placenta percreta. The results from 38 women with PP suggest that the serum concentrations of IMA and the oxidative stress parameters may be able to predict PP in cases of uncertainty. What are the implications of these findings for clinical practice and/or further research? The implication of these findings shed light on understanding the pathogenesis of PP for further research.

Chemokine scavenger D6 is expressed by trophoblasts and aids the survival of mouse embryos transferred into allogeneic recipients.

PubMed

Madigan, Judith; Freeman, Dilys J; Menzies, Fiona; Forrow, Steve; Nelson, Scott M; Young, Anne; Sharkey, Andrew; Moffett, Ashley; Graham, Gerard J; Greer, Ian A; Rot, Antal; Nibbs, Robert J B

2010-03-15

Proinflammatory CC chemokines are thought to drive recruitment of maternal leukocytes into gestational tissues and regulate extravillous trophoblast migration. The atypical chemokine receptor D6 binds many of these chemokines and is highly expressed by the human placenta. D6 is thought to act as a chemokine scavenger because, when ectopically expressed in cell lines in vitro, it efficiently internalizes proinflammatory CC chemokines and targets them for destruction in the absence of detectable chemokine-induced signaling. Moreover, D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient fetuses in D6-deficient female mice show increased susceptibility to inflammation-driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with specific intracellular distribution patterns, in trophoblast-derived cells in human placenta, decidua, and gestational membranes throughout pregnancy and in trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for the first time, that endogenous D6 in a human choriocarcinoma-derived cell line can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can specifically associate with human syncytiotrophoblasts in term placenta in situ. Moreover, despite strong chemokine production by gestational tissues, levels of D6-binding chemokines in maternal plasma decrease during pregnancy, even in women with pre-eclampsia, a disease associated with increased maternal inflammation. In mice, D6 is not required for syngeneic or semiallogeneic fetal survival in unchallenged mice, but interestingly, it does suppress fetal resorption after embryo transfer into fully allogeneic recipients. These data support the view that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface and that, in some circumstances, this can help to ensure fetal survival.

Evidence for Differential Glycosylation of Trophoblast Cell Types*

PubMed Central

Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E.; Longtine, Mark S.; Schust, Danny J.; Haslam, Stuart M.; Blois, Sandra M.; Dell, Anne; Clark, Gary F.

2016-01-01

Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3–4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2–3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2–3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. PMID:26929217

Evidence for Differential Glycosylation of Trophoblast Cell Types.

PubMed

Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E; Longtine, Mark S; Schust, Danny J; Haslam, Stuart M; Blois, Sandra M; Dell, Anne; Clark, Gary F

2016-06-01

Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Interleukin 18 messenger RNA and proIL-18 protein expression in chorioamniotic membranes from pregnant women with preterm prelabor rupture of membranes.

PubMed

Polettini, Jossimara; Vieira, Eliane Passarelli; Santos, Mariana Perlati dos; Peraçoli, José Carlos; Witkin, Steven S; da Silva, Márcia Guimarães

2012-04-01

To quantify the expression of IL-18 mRNA and protein in the chorioamniotic membranes of pregnant women with PPROM and correlate expression with histological chorioamnionitis. A case control study that included 42 pregnant women not in labor in the following groups: PPROM (n=28) and controls with intact membranes submitted to selective cesarean section at term (n=14). Expression of IL-18 mRNA in chorioamniotic membranes was determined by real-time polymerase chain reaction, and IL-18 protein expression was measured by western blot. Histopathological analyses and immunolocalization of IL-18 by immunohistochemistry were also performed. Analyses were performed using the Mann-Whitney or Fisher's exact tests and the group effect was considered significant if the adjusted p-values were <0.05 and the magnitude of change was greater than 2-fold for mRNA expression. IL-18 mRNA was present in 100% of samples and no difference in expression was observed between term vs. PPROM membranes (fold-change 0.12; p=0.88). In the PPROM group, no difference was observed in IL-18 mRNA regarding gestational age (fold-change 0.11; p=0.42) or the presence of histological chorioamnionitis (fold-change 0.26; p=0.15). ProIL-18 was present in all samples. IL-18 was immunolocalized to amnion, chorion and decidua cells, with intense immunohistochemical staining at the choriodecidual junction. Chorioamniotic membranes are sources of IL-18 mRNA and proIL-18, and their expression is unrelated to PPROM or histological chorioamnionitis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Tree-growth analyses to estimate tree species' drought tolerance.

PubMed

Eilmann, Britta; Rigling, Andreas

2012-02-01

Climate change is challenging forestry management and practices. Among other things, tree species with the ability to cope with more extreme climate conditions have to be identified. However, while environmental factors may severely limit tree growth or even cause tree death, assessing a tree species' potential for surviving future aggravated environmental conditions is rather demanding. The aim of this study was to find a tree-ring-based method suitable for identifying very drought-tolerant species, particularly potential substitute species for Scots pine (Pinus sylvestris L.) in Valais. In this inner-Alpine valley, Scots pine used to be the dominating species for dry forests, but today it suffers from high drought-induced mortality. We investigate the growth response of two native tree species, Scots pine and European larch (Larix decidua Mill.), and two non-native species, black pine (Pinus nigra Arnold) and Douglas fir (Pseudotsuga menziesii Mirb. var. menziesii), to drought. This involved analysing how the radial increment of these species responded to increasing water shortage (abandonment of irrigation) and to increasingly frequent drought years. Black pine and Douglas fir are able to cope with drought better than Scots pine and larch, as they show relatively high radial growth even after irrigation has been stopped and a plastic growth response to drought years. European larch does not seem to be able to cope with these dry conditions as it lacks the ability to recover from drought years. The analysis of trees' short-term response to extreme climate events seems to be the most promising and suitable method for detecting how tolerant a tree species is towards drought. However, combining all the methods used in this study provides a complete picture of how water shortage could limit species.

Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.

PubMed

Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P

2016-12-01

Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O 2 ) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O 2 ) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction. © 2016 by the Society for the Study of Reproduction, Inc.

Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

PubMed

Kawasaki, Kaoru; Kondoh, Eiji; Minamiguchi, Sachiko; Matsuda, Fumihiko; Higasa, Koichiro; Fujita, Kohei; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

2016-08-01

A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby. © 2016 Japan Society of Obstetrics and Gynecology.

Vegetation and environmental responses to climate forcing during the Last Glacial Maximum and deglaciation in the East Carpathians: attenuated response to maximum cooling and increased biomass burning

NASA Astrophysics Data System (ADS)

Magyari, E. K.; Veres, D.; Wennrich, V.; Wagner, B.; Braun, M.; Jakab, G.; Karátson, D.; Pál, Z.; Ferenczy, Gy; St-Onge, G.; Rethemeyer, J.; Francois, J.-P.; von Reumont, F.; Schäbitz, F.

2014-12-01

The Carpathian Mountains were one of the main mountain reserves of the boreal and cool temperate flora during the Last Glacial Maximum (LGM) in East-Central Europe. Previous studies demonstrated Lateglacial vegetation dynamics in this area; however, our knowledge on the LGM vegetation composition is very limited due to the scarcity of suitable sedimentary archives. Here we present a new record of vegetation, fire and lacustrine sedimentation from the youngest volcanic crater of the Carpathians (Lake St Anne, Lacul Sfânta Ana, Szent-Anna-tó) to examine environmental change in this region during the LGM and the subsequent deglaciation. Our record indicates the persistence of boreal forest steppe vegetation (with Pinus, Betula, Salix, Populus and Picea) in the foreland and low mountain zone of the East Carpathians and Juniperus shrubland at higher elevation. We demonstrate attenuated response of the regional vegetation to maximum global cooling. Between ˜22,870 and 19,150 cal yr BP we find increased regional biomass burning that is antagonistic with the global trend. Increased regional fire activity suggests extreme continentality likely with relatively warm and dry summers. We also demonstrate xerophytic steppe expansion directly after the LGM, from ˜19,150 cal yr BP, and regional increase in boreal woodland cover with Pinus and Betula from 16,300 cal yr BP. Plant macrofossils indicate local (950 m a.s.l.) establishment of Betula nana and Betula pubescens at 15,150 cal yr BP, Pinus sylvestris at 14,700 cal yr BP and Larix decidua at 12,870 cal yr BP. Pollen data furthermore support population genetic inferences regarding the regional presence of some temperate deciduous trees during the LGM (Fagus sylvatica, Corylus avellana, Fraxinus excelsior). Our sedimentological data also demonstrate intensified aeolian dust accumulation between 26,000 and 20,000 cal yr BP.

Double sac sign and intradecidual sign in early pregnancy: interobserver reliability and frequency of occurrence.

PubMed

Doubilet, Peter M; Benson, Carol B

2013-07-01

To assess the interobserver agreement, frequency of occurrence, and prognostic importance of the double sac sign (DSS), intradecidual sign (IDS), and other sonographic findings in early intrauterine pregnancies. We retrospectively identified all sonograms obtained between January 1, 2006, and December 31, 2011, in which: (1) the scan demonstrated an intrauterine fluid collection without a yolk sac or embryo; (2) a follow-up scan confirmed an intrauterine pregnancy; and (3) the first-trimester outcome was known. Each coinvestigator characterized the 199 study sonograms as demonstrating or not demonstrating a DSS or an IDS, based on judgment about whether the scan met published criteria defining these signs. Interobserver agreement was poor for the DSS (κ= 0.24) and IDS (κ= 0.23). Scans frequently demonstrated neither sign: 150 cases (75.4%) if we considered a sign to be present when both investigators graded it as present and 69 cases (34.7%) using the looser criterion that either graded it as present. The presence of a DSS or an IDS was unrelated to the β-human chorionic gonadotropin (β-hCG) value (P > .05, t test, all comparisons). An inner echogenic ring was present in 158 cases (79.4%), and the decidua was brighter peripherally than centrally in 102 (51.3%). The first-trimester outcome was unrelated to the presence of a DSS or an IDS, presence of an inner echogenic ring, or decidual appearance (P > .05, χ(2), all comparisons). The sonographic appearance of early gestational sacs, before visualization of a yolk sac or embryo, is highly variable. The DSS and IDS are often absent; there is poor interobserver agreement regarding these signs; and the prognosis is unrelated to their presence or absence. A round or oval intrauterine fluid collection in a woman with positive β-hCG should be treated as a gestational sac until proven otherwise, regardless of whether it demonstrates a DSS or an IDS.

Time since death and decay rate constants of Norway spruce and European larch deadwood in subalpine forests determined using dendrochronology and radiocarbon dating

NASA Astrophysics Data System (ADS)

Petrillo, M.; Cherubini, P.; Fravolini, G.; Ascher, J.; Schärer, M.; Synal, H.-A.; Bertoldi, D.; Camin, F.; Larcher, R.; Egli, M.

2015-09-01

Due to the large size and highly heterogeneous spatial distribution of deadwood, the time scales involved in the coarse woody debris (CWD) decay of Picea abies (L.) Karst. and Larix decidua Mill. in Alpine forests have been poorly investigated and are largely unknown. We investigated the CWD decay dynamics in an Alpine valley in Italy using the five-decay class system commonly employed for forest surveys, based on a macromorphological and visual assessment. For the decay classes 1 to 3, most of the dendrochronological samples were cross-dated to assess the time that had elapsed since tree death, but for decay classes 4 and 5 (poorly preserved tree rings) and some others not having enough tree rings, radiocarbon dating was used. In addition, density, cellulose and lignin data were measured for the dated CWD. The decay rate constants for spruce and larch were estimated on the basis of the density loss using a single negative exponential model. In the decay classes 1 to 3, the ages of the CWD were similar varying between 1 and 54 years for spruce and 3 and 40 years for larch with no significant differences between the classes; classes 1-3 are therefore not indicative for deadwood age. We found, however, distinct tree species-specific differences in decay classes 4 and 5, with larch CWD reaching an average age of 210 years in class 5 and spruce only 77 years. The mean CWD rate constants were 0.012 to 0.018 yr-1 for spruce and 0.005 to 0.012 yr-1 for larch. Cellulose and lignin time trends half-lives (using a multiple-exponential model) could be derived on the basis of the ages of the CWD. The half-lives for cellulose were 21 yr for spruce and 50 yr for larch. The half-life of lignin is considerably higher and may be more than 100 years in larch CWD.

How to make a tree ring: Coupling stem water flow and cambial activity in mature Alpine conifers

NASA Astrophysics Data System (ADS)

Peters, Richard L.; Frank, David C.; Treydte, Kerstin; Steppe, Kathy; Kahmen, Ansgar; Fonti, Patrick

2017-04-01

Inter-annual tree-ring measurements are used to understand tree-growth responses to climatic variability and reconstruct past climate conditions. In parallel, mechanistic models use experimentally defined plant-atmosphere interactions to explain past growth responses and predict future environmental impact on forest productivity. Yet, substantial inconsistencies within mechanistic model ensembles and mismatches with empirical data indicate that significant progress is still needed to understand the processes occurring at an intra-annual resolution that drive annual growth. However, challenges arise due to i) few datasets describing climatic responses of high-resolution physiological processes over longer time-scales, ii) uncertainties on the main mechanistic process limiting radial stem growth and iii) complex interactions between multiple environmental factors which obscure detection of the main stem growth driver, generating a gap between our understanding of intra- and inter-annual growth mechanisms. We attempt to bridge the gap between inter-annual tree-ring width and sub-daily radial stem-growth and provide a mechanistic perspective on how environmental conditions affect physiological processes that shape tree rings in conifers. We combine sub-hourly sap flow and point dendrometer measurements performed on mature Alpine conifers (Larix decidua) into an individual-based mechanistic tree-growth model to simulate sub-hourly cambial activity. The monitored trees are located along a high elevational transect in the Swiss Alps (Lötschental) to analyse the effect of increasing temperature. The model quantifies internal tree hydraulic pathways that regulate the turgidity within the cambial zone and induce cell enlargement for radial growth. The simulations are validated against intra-annual growth patterns derived from xylogenesis data and anatomical analyses. Our efforts advance the process-based understanding of how climate shapes the annual tree-ring structures and could potentially improve our ability to reconstruct the climate of the past and predict future growth under changing climate.

Progesterone, Inflammatory Cytokine (TNF-α), and Oxidative Stress (H2O2) Regulate Progesterone Receptor Membrane Component 1 Expression in Fetal Membrane Cells.

PubMed

Meng, Yan; Murtha, Amy P; Feng, Liping

2016-09-01

Progesterone receptor membrane component 1 (PGRMC1) is an important novel mediator of progesterone (P4) function in fetal membrane cells. We demonstrated previously that PGRMC1 is differentially expressed in fetal membranes among pregnancy subjects and diminished in preterm premature rupture of membrane subjects. In the current study, we aim to elucidate whether PGRMC1 expression is regulated by P4, tumor necrosis factor α (TNF-α), and H2O2 in fetal membrane cells. Primary cultured membrane cells were serum starved for 24 hours followed by treatments of P4, 17 hydroxyprogesterone caproate, and medroxyprogesterone 17 acetate (MPA) at 10(-7) mol/L with ethanol as vehicle control; TNF-α at 10, 20, and 50 ng/mL with phosphate-buffered saline (PBS) as control; and H2O2 at 10 and 100 μmol/L with culture media as control for 24, 48, and 72 hours. The messenger RNA (mRNA) and protein expression of PGRMC1 was quantified using polymerase chain reaction and Western blotting, respectively. We found that PGRMC1 protein expression was regulated by MPA, TNF-α, and H2O2 in a dose-dependent manner. This regulation is also specific to the type of cell (amnion, chorion, or decidua). The upregulation of PGRMC1 by MPA might be mediated through glucocorticoid receptor (GR) demonstrated using amnion and chorion cells model with GR knockdown by specific small interfering RNA transfection. The mRNA expression of PGRMC1 was decreased by H2O2 (100 μmol/L) treatment in amnion cells, which might ultimately result in downregulation of PGRMC1 protein as our data demonstrated. None of other treatments changed PGRMC1 mRNA level in these cells. We conclude that these stimuli act as regulatory factors of PGRMC1 in a cell-specific manner. © The Author(s) 2016.

Immunodetection of 11 beta-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization.

PubMed

Shimojo, M; Ricketts, M L; Petrelli, M D; Moradi, P; Johnson, G D; Bradwell, A R; Hewison, M; Howie, A J; Stewart, P M

1997-03-01

11 beta-Hydroxysteroid dehydrogenase (11 beta HSI) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11 beta HSD2 gene, suggest that it is the 11 beta HSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11 beta HSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11 beta HSD2 in mineralocorticoid target tissues. The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11 beta HSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11 beta HSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 micron indicated significant 11 beta HSD2 immunofluorescence in the nucleus. In human kidney, colon, and salivary gland, 11 beta HSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11 beta HSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the interaction between the MR and aldosterone or cortisol is in part a nuclear event.

[The morphology, typical combinations of polymorphic genes of hemostasis, and specific features of the pathogenesis of retrochorial hematoma in missed abortion].

PubMed

Milovanov, A P; Kuznetsova, N B; Bushtyreva, I O

to identify mutations and hemostatic gene polymorphisms typical for retrochorial hematoma (RCH) and to study its pathogenesis in missed abortion. A PCR assay was used to detect the genetic forms of thrombophilia in 270 patients with ultrasonographically verified RCH. Logistic regression analysis revealed that with the F7 (proconvertin, coagulation factor (CF) VII G10976A polymorphism or with the F13 (fibrinase, CF XIII) G>T, or FGB (fibrinogen β-chain) G455A polymorphism, the risk of RCH was 2.72, 2.16, and 1.92 times higher, respectively. First trimester missed abortion was found in 42 (15.5%) cases; among them there were 24 (8.8%) women with different polymorphism combinations: F7 (G10976A), F13 (fibrinase, G>T), FGB (G455A). A total of 18 cases of missed abortion due to morphologically verified endometritis, endocrinopathies, and antiphospholipid syndrome were excluded from the sample. Compared to the morphology of medical abortions of the same period (16 women), patients with polymorphic genes of hemostasis were found to have statistically significant incomplete endometrial decidualization, thinning or absence of a Rohr's fibrinoid layer, a smaller number and shortening of syncytiotrophoblast microvilli, and the maximum amount of dissecting hemorrhage and RCH in the utero-chorionic region. The stages of RCH pathogenesis were determined; these included penetration of maternal erythrocytes deep into the decidua ~ dissociation of a layer of decidual cells with impairment of a «hemostatic envelope» ~ formation of RCH with a dense network of fibrin threads ~ final necrosis of surrounding cells and tissues. The investigators identified for the first time the typical combinations of polymorphic genes of predisposition to a high risk for RCH; its complete formation requires additional changes in maternal and placental components that provide local hemostasis.

Fire, Fuel Composition and Resilience Threshold in Subalpine Ecosystem

PubMed Central

Blarquez, Olivier; Carcaillet, Christopher

2010-01-01

Background Forecasting the effects of global changes on high altitude ecosystems requires an understanding of the long-term relationships between biota and forcing factors to identify resilience thresholds. Fire is a crucial forcing factor: both fuel build-up from land-abandonment in European mountains, and more droughts linked to global warming are likely to increase fire risks. Methods To assess the vegetation response to fire on a millennium time-scale, we analyzed evidence of stand-to-local vegetation dynamics derived from sedimentary plant macroremains from two subalpine lakes. Paleobotanical reconstructions at high temporal resolution, together with a fire frequency reconstruction inferred from sedimentary charcoal, were analyzed by Superposed Epoch Analysis to model plant behavior before, during and after fire events. Principal Findings We show that fuel build-up from arolla pine (Pinus cembra) always precedes fires, which is immediately followed by a rapid increase of birch (Betula sp.), then by ericaceous species after 25–75 years, and by herbs after 50–100 years. European larch (Larix decidua), which is the natural co-dominant species of subalpine forests with Pinus cembra, is not sensitive to fire, while the abundance of Pinus cembra is altered within a 150-year period after fires. A long-term trend in vegetation dynamics is apparent, wherein species that abound later in succession are the functional drivers, loading the environment with fuel for fires. This system can only be functional if fires are mainly driven by external factors (e.g. climate), with the mean interval between fires being longer than the minimum time required to reach the late successional stage, here 150 years. Conclusion Current global warming conditions which increase drought occurrences, combined with the abandonment of land in European mountain areas, creates ideal ecological conditions for the ignition and the spread of fire. A fire return interval of less than 150 years would threaten the dominant species and might override the resilience of subalpine forests. PMID:20814580

Similar variation in carbon storage between deciduous and evergreen treeline species across elevational gradients.

PubMed

Fajardo, Alex; Piper, Frida I; Hoch, Günter

2013-08-01

The most plausible explanation for treeline formation so far is provided by the growth limitation hypothesis (GLH), which proposes that carbon sinks are more restricted by low temperatures than by carbon sources. Evidence supporting the GLH has been strong in evergreen, but less and weaker in deciduous treeline species. Here a test is made of the GLH in deciduous-evergreen mixed species forests across elevational gradients, with the hypothesis that deciduous treeline species show a different carbon storage trend from that shown by evergreen species across elevations. Tree growth and concentrations of non-structural carbohydrates (NSCs) in foliage, branch sapwood and stem sapwood tissues were measured at four elevations in six deciduous-evergreen treeline ecotones (including treeline) in the southern Andes of Chile (40°S, Nothofagus pumilio and Nothofagus betuloides; 46°S, Nothofagus pumilio and Pinus sylvestris) and in the Swiss Alps (46°N, Larix decidua and Pinus cembra). Tree growth (basal area increment) decreased with elevation for all species. Regardless of foliar habit, NSCs did not deplete across elevations, indicating no shortage of carbon storage in any of the investigated tissues. Rather, NSCs increased significantly with elevation in leaves (P < 0·001) and branch sapwood (P = 0·012) tissues. Deciduous species showed significantly higher NSCs than evergreens for all tissues; on average, the former had 11 % (leaves), 158 % (branch) and 103 % (sapwood) significantly (P < 0·001) higher NSCs than the latter. Finally, deciduous species had higher NSC (particularly starch) increases with elevation than evergreens for stem sapwood, but the opposite was true for leaves and branch sapwood. Considering the observed decrease in tree growth and increase in NSCs with elevation, it is concluded that both deciduous and evergreen treeline species are sink limited when faced with decreasing temperatures. Despite the overall higher requirements of deciduous tree species for carbon storage, no indication was found of carbon limitation in deciduous species in the alpine treeline ecotone.

Growth and phenology of three dwarf shrub species in a six-year soil warming experiment at the alpine treeline.

PubMed

Anadon-Rosell, Alba; Rixen, Christian; Cherubini, Paolo; Wipf, Sonja; Hagedorn, Frank; Dawes, Melissa A

2014-01-01

Global warming can have substantial impacts on the phenological and growth patterns of alpine and Arctic species, resulting in shifts in plant community composition and ecosystem dynamics. We evaluated the effects of a six-year experimental soil warming treatment (+4°C, 2007-2012) on the phenology and growth of three co-dominant dwarf shrub species growing in the understory of Larix decidua and Pinus uncinata at treeline in the Swiss Alps. We monitored vegetative and reproductive phenology of Vaccinium myrtillus, Vaccinium gaultherioides and Empetrum hermaphroditum throughout the early growing season of 2012 and, following a major harvest at peak season, we measured the biomass of above-ground ramet fractions. For all six years of soil warming we measured annual shoot growth of the three species and analyzed ramet age and xylem ring width of V. myrtillus. Our results show that phenology of the three species was more influenced by snowmelt timing, and also by plot tree species (Larix or Pinus) in the case of V. myrtillus, than by soil warming. However, the warming treatment led to increased V. myrtillus total above-ground ramet biomass (+36% in 2012), especially new shoot biomass (+63% in 2012), as well as increased new shoot increment length and xylem ring width (+22% and +41%, respectively; average for 2007-2012). These results indicate enhanced overall growth of V. myrtillus under soil warming that was sustained over six years and was not caused by an extended growing period in early summer. In contrast, E. hermaphroditum only showed a positive shoot growth response to warming in 2011 (+21%), and V. gaultherioides showed no significant growth response. Our results indicate that V. myrtillus might have a competitive advantage over the less responsive co-occurring dwarf shrub species under future global warming.

Vegetation changes and timberline fluctuations in the Central Alps as indicators of holocene climatic oscillations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wick, L.; Tinner, W.

Pollen and plant-macrofossil data are presented for two lakes near the timberline in the Italian (Lago Basso, 2250 m) and Swiss Central Alps (Gouille Rion, 2343 m). The reforestation at both sites started at 9700-9500 BP with Pinus cembra, Larix decidua, and Betula. The timberline reached its highest elevation between 8700 and 5000 BP and retreated after 5000 BP, due to a mid-Holocene climatic change and increasing human impact since about 3500 BP (Bronze Age). The expansion of Picea abies at Lago Basso between ca. 7500 and 6200 BP was probably favored by cold phases accompanied by increased oceanicity, whereasmore » in the area of Gouille Rion, where spruce expanded rather late (between 4500 and 3500 BP), human influence equality might have been important. The mass expansion of Alnus viridis between ca. 5000 and 3500 BP probably can be related to both climatic change and human activity at timberline. During the early and middle Holocene a series of timberline fluctuations is recorded as declines in pollen and macrofossil concentrations of the major tree species, and as increases in nonarboreal pollen in the pollen percentage diagram of Gouille Rion. Most of the periods of low timberline can be correlated by radiocarbon dating the climatic changes in the Alps as indicated by glacier advances in combination with palynological records, solifluction, and dendroclimatical data. Lago Basso and Gouille Rion are the only sites in the Alps showing complete palaeobotanical records of cold phases between 10,000 and 2000 BP with very good time control. The altitudinal range of the Holocene treeline fluctuations caused by climate most likely was not more than 100 to 150 m. A possible correlation of a cold period at ca. 7500-6500 BP (Misox oscillation) in the Alps is made with paleoecological data from North American and Scandinavia and a climate signal in the GRIP ice core from central Greenland 8200 yr ago (ca. 7400 yr uncal. BP).« less

Cesarean scar pregnancy and early placenta accreta share common histology.

PubMed

Timor-Tritsch, I E; Monteagudo, A; Cali, G; Palacios-Jaraquemada, J M; Maymon, R; Arslan, A A; Patil, N; Popiolek, D; Mittal, K R

2014-04-01

To determine, by evaluation of histological slides, images and descriptions of early (second-trimester) placenta accreta (EPA) and placental implantation in cases of Cesarean scar pregnancy (CSP), whether these are pathologically indistinguishable and whether they both represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester. The database of a previously published review of CSP and EPA was used to identify articles with histopathological descriptions and electronic images for pathological review. When possible, microscopic slides and/or paraffin blocks were obtained from the original researchers. We also included from our own institutions cases of CSP and EPA for which pathology specimens were available. Two pathologists examined all the material independently and, blinded to each other's findings, provided a pathological diagnosis based on microscopic appearance. Interobserver agreement in diagnosis was determined. Forty articles were identified, which included 31 cases of CSP and 13 cases of EPA containing histopathological descriptions and/or images of the pathology. We additionally included six cases of CSP and eight cases of EPA from our own institutions, giving a total of 58 cases available for histological evaluation (37 CSP and 21 EPA) containing clear definitions of morbidly adherent placenta. In the 29 cases for which images/slides were available for histopathological evaluation, both pathologists attested to the various degrees of myometrial and/or scar tissue invasion by placental villi with scant or no intervening decidua, consistent with the classic definition of morbidly adherent placenta. Based on the reviewed material, cases with a diagnosis of EPA and those with a diagnosis of CSP showed identical histopathological features. Interobserver correlation was high (kappa = 0.93). EPA and placental implantation in CSP are histopathologically indistinguishable and may represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between protein expression of FOXP3 and level of FOXP3 promoter methylation in recurrent spontaneous abortion.

PubMed

Hou, Wenhui; Li, Zhuyu; Li, Yinguang; Fang, Liyuan; Li, Jie; Huang, Jia; Li, Xiaoqing; You, Zeshan

2016-11-01

The aim of this study was to investigate the level of Forkhead box P3 (FOXP3) promoter methylation and protein expression in recurrent spontaneous abortion and to elucidate the pathogenesis of unexplained recurrent spontaneous abortion (URSA). We assessed a total of 56 URSA patients with a normal embryo, 24 recurrent spontaneous abortion (RSA) patients with an abnormal embryo (as control group 1), and 39 normal pregnant women (as control group 2). The expression of FOXP3 protein in deciduas was assessed through Western blot, and the level of FOXP3 promoter methylation was detected using bisulfite-assisted genomic sequencing polymerase chain reaction. The expressing quantity of FOXP3 protein in the URSA group was significantly lower than that in control groups 1 and 2, both with a P-value < 0.05. By contrast, no statistical difference was observed in the expressing quantity of FOXP3 protein of the two control groups (P = 0.212). The FOXP3 promoter methylation level in the URSA group was significantly higher than that in the two control groups, both of which exhibited a statistical difference of P-values < 0.05. Meanwhile, no statistical difference was observed in the FOXP3 promoter methylation level of the two control groups (P = 0.141). A negative correlation was found between the FOXP3 promoter methylation level and the expressing quantity of FOXP3 protein (r = -0.861, P < 0.05). Increasing FOXP3 promoter methylation levels may cause abnormal immune tolerance through the downregulation expression of the FOXP3 protein, which in turn leads to URSA. © 2016 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.

Histopathological Changes in the Chorionic Villi and Endometrial Decidual Tissues in the Product of Conception of Spontaneous Abortion Cases.

PubMed

Makaju, R; Shrestha, S; Sharma, S; Dhakal, R; Bhandari, S; Shrestha, A; Tamrakar, S

2015-01-01

Background Spontaneous abortion refers to a pregnancy that ends spontaneously before the fetus has reached a viable gestational age or expulsion or extraction of an embryo or fetus weighing 500 g or less from its mother. The Maternal Mortality Morbidity Survey of Nepal 2008/09 reported that 7% of maternal deaths in Nepal were due to complications related to abortion. Objective The main objective of this study was to examine the histopathological changes in the chorionic villi and endometrial decidual tissue in products of conception obtained from women with spontaneous abortion. Method This is a retrospective study of 111 patients admitted in the Department of Obstetrics and Gynecology at Dhulikhel Hospital, Kathmandu University Hospital (DH-KUH) with the diagnosis of spontaneous abortion during the period of January 2013 to January 2014. Result Among 111 cases of spontaneous abortions, products of conception was seen in 73 (65.77%) and with only one cases of choriocarcinoma. Majority of cases belongs to age group 21-30 years. The most common decidual changes were inflammation (41.4%) followed by fibrin deposition 29.7%. Majority of the cases shows hydropic changes as histopathological changes in chorionic villi. In the present study, minimum age of lady was 15 years and the maximum age was 45 years and the mean age was 25.09±5.58 years at the time of abortion. Among the cases, maximum 69 (62.2%) of them belonged to age group 21-30 years. Correlating the age group with number of abortions was found to be significantly different (Chi-square= 92.35, df= 3, p < 0.001) among four different age groups. Conclusion The histopathological diagnosis of spontaneous abortion will help in further management of the patient. Further study is required to know the cause of different histopathlogical changes in villi as well as in the decidua.

Soil warming and CO2 enrichment induce biomass shifts in alpine tree line vegetation.

PubMed

Dawes, Melissa A; Philipson, Christopher D; Fonti, Patrick; Bebi, Peter; Hättenschwiler, Stephan; Hagedorn, Frank; Rixen, Christian

2015-05-01

Responses of alpine tree line ecosystems to increasing atmospheric CO2 concentrations and global warming are poorly understood. We used an experiment at the Swiss tree line to investigate changes in vegetation biomass after 9 years of free air CO2 enrichment (+200 ppm; 2001-2009) and 6 years of soil warming (+4 °C; 2007-2012). The study contained two key tree line species, Larix decidua and Pinus uncinata, both approximately 40 years old, growing in heath vegetation dominated by dwarf shrubs. In 2012, we harvested and measured biomass of all trees (including root systems), above-ground understorey vegetation and fine roots. Overall, soil warming had clearer effects on plant biomass than CO2 enrichment, and there were no interactive effects between treatments. Total plant biomass increased in warmed plots containing Pinus but not in those with Larix. This response was driven by changes in tree mass (+50%), which contributed an average of 84% (5.7 kg m(-2) ) of total plant mass. Pinus coarse root mass was especially enhanced by warming (+100%), yielding an increased root mass fraction. Elevated CO2 led to an increased relative growth rate of Larix stem basal area but no change in the final biomass of either tree species. Total understorey above-ground mass was not altered by soil warming or elevated CO2 . However, Vaccinium myrtillus mass increased with both treatments, graminoid mass declined with warming, and forb and nonvascular plant (moss and lichen) mass decreased with both treatments. Fine roots showed a substantial reduction under soil warming (-40% for all roots <2 mm in diameter at 0-20 cm soil depth) but no change with CO2 enrichment. Our findings suggest that enhanced overall productivity and shifts in biomass allocation will occur at the tree line, particularly with global warming. However, individual species and functional groups will respond differently to these environmental changes, with consequences for ecosystem structure and functioning. © 2014 John Wiley & Sons Ltd.

Dissecting the space-time structure of tree-ring datasets using the partial triadic analysis.

PubMed

Rossi, Jean-Pierre; Nardin, Maxime; Godefroid, Martin; Ruiz-Diaz, Manuela; Sergent, Anne-Sophie; Martinez-Meier, Alejandro; Pâques, Luc; Rozenberg, Philippe

2014-01-01

Tree-ring datasets are used in a variety of circumstances, including archeology, climatology, forest ecology, and wood technology. These data are based on microdensity profiles and consist of a set of tree-ring descriptors, such as ring width or early/latewood density, measured for a set of individual trees. Because successive rings correspond to successive years, the resulting dataset is a ring variables × trees × time datacube. Multivariate statistical analyses, such as principal component analysis, have been widely used for extracting worthwhile information from ring datasets, but they typically address two-way matrices, such as ring variables × trees or ring variables × time. Here, we explore the potential of the partial triadic analysis (PTA), a multivariate method dedicated to the analysis of three-way datasets, to apprehend the space-time structure of tree-ring datasets. We analyzed a set of 11 tree-ring descriptors measured in 149 georeferenced individuals of European larch (Larix decidua Miller) during the period of 1967-2007. The processing of densitometry profiles led to a set of ring descriptors for each tree and for each year from 1967-2007. The resulting three-way data table was subjected to two distinct analyses in order to explore i) the temporal evolution of spatial structures and ii) the spatial structure of temporal dynamics. We report the presence of a spatial structure common to the different years, highlighting the inter-individual variability of the ring descriptors at the stand scale. We found a temporal trajectory common to the trees that could be separated into a high and low frequency signal, corresponding to inter-annual variations possibly related to defoliation events and a long-term trend possibly related to climate change. We conclude that PTA is a powerful tool to unravel and hierarchize the different sources of variation within tree-ring datasets.

Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy.

PubMed

Horne, A W; Duncan, W C; King, A E; Burgess, S; Lourenco, P C; Cornes, P; Ghazal, P; Williams, A R; Udby, L; Critchley, H O D

2009-05-01

Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was inversely proportional to serum hCG concentrations (P < 0.001). Stimulation of endometrial epithelial cells with hCG in vitro caused a reduction in CRISP-3 expression (P < 0.01). The measurement of CRISP-3 in endometrium could provide an additional tool in the diagnosis of failing early pregnancy of unknown location. The absence of a local reduction in expression of CRISP-3 in decidualized endometrium of women with EP may be due to reduced exposure to hCG due to the ectopic location of the trophoblast.

Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

PubMed

Raman, Kripa; Wang, Huaqing; Troncone, Michael J; Khan, Waliul I; Pare, Guillaume; Terry, Jefferson

2015-01-01

Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level expression and demonstrate that IgJ expression was largely attributable to the presence of plasma cells as part of chronic deciduitis and that IgA positive plasma cells are associated with chronic deciduitis occurring in combination with chronic chorioamnionitis and chronic villitis of unknown etiology but not with isolated chronic deciduitis.

Growth and Phenology of Three Dwarf Shrub Species in a Six-Year Soil Warming Experiment at the Alpine Treeline

PubMed Central

Anadon-Rosell, Alba; Rixen, Christian; Cherubini, Paolo; Wipf, Sonja; Hagedorn, Frank; Dawes, Melissa A.

2014-01-01

Global warming can have substantial impacts on the phenological and growth patterns of alpine and Arctic species, resulting in shifts in plant community composition and ecosystem dynamics. We evaluated the effects of a six-year experimental soil warming treatment (+4°C, 2007–2012) on the phenology and growth of three co-dominant dwarf shrub species growing in the understory of Larix decidua and Pinus uncinata at treeline in the Swiss Alps. We monitored vegetative and reproductive phenology of Vaccinium myrtillus, Vaccinium gaultherioides and Empetrum hermaphroditum throughout the early growing season of 2012 and, following a major harvest at peak season, we measured the biomass of above-ground ramet fractions. For all six years of soil warming we measured annual shoot growth of the three species and analyzed ramet age and xylem ring width of V. myrtillus. Our results show that phenology of the three species was more influenced by snowmelt timing, and also by plot tree species (Larix or Pinus) in the case of V. myrtillus, than by soil warming. However, the warming treatment led to increased V. myrtillus total above-ground ramet biomass (+36% in 2012), especially new shoot biomass (+63% in 2012), as well as increased new shoot increment length and xylem ring width (+22% and +41%, respectively; average for 2007–2012). These results indicate enhanced overall growth of V. myrtillus under soil warming that was sustained over six years and was not caused by an extended growing period in early summer. In contrast, E. hermaphroditum only showed a positive shoot growth response to warming in 2011 (+21%), and V. gaultherioides showed no significant growth response. Our results indicate that V. myrtillus might have a competitive advantage over the less responsive co-occurring dwarf shrub species under future global warming. PMID:24956273

Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome

PubMed Central

Laurence, Jessica A.; Leemaqz, Shalem; O’Leary, Sean; Bianco-Miotto, Tina; Du, Jing; Anderson, Paul H.; Roberts, Claire T.

2015-01-01

Vitamin D deficiency has been implicated in the pathogenesis of several pregnancy complications attributed to impaired or abnormal placental function, but there are few clues indicating the mechanistic role of vitamin D in their pathogenesis. To further understand the role of vitamin D receptor (VDR)-mediated activity in placental function, we used heterozygous Vdr ablated C57Bl6 mice to assess fetal growth, morphological parameters and global gene expression in Vdr null placentae. Twelve Vdr +/- dams were mated at 10–12 weeks of age with Vdr +/- males. At day 18.5 of the 19.5 day gestation in our colony, females were euthanised and placental and fetal samples were collected, weighed and subsequently genotyped as either Vdr +/+, Vdr +/- or Vdr -/-. Morphological assessment of placentae using immunohistochemistry was performed and RNA was extracted and subject to microarray analysis. This revealed 25 genes that were significantly differentially expressed between Vdr +/+ and Vdr -/- placentae. The greatest difference was a 6.47-fold change in expression of Cyp24a1 which was significantly lower in the Vdr -/- placentae (P<0.01). Other differentially expressed genes in Vdr -/- placentae included those involved in RNA modification (Snord123), autophagy (Atg4b), cytoskeletal modification (Shroom4), cell signalling (Plscr1, Pex5) and mammalian target of rapamycin (mTOR) signalling (Deptor and Prr5). Interrogation of the upstream sequence of differentially expressed genes identified that many contain putative vitamin D receptor elements (VDREs). Despite the gene expression differences, this did not contribute to any differences in overall placental morphology, nor was function affected as there was no difference in fetal growth as determined by fetal weight near term. Given our dams still expressed a functional VDR gene, our results suggest that cross-talk between the maternal decidua and the placenta, as well as maternal vitamin D status, may be more important in determining pregnancy outcome than conceptus expression of VDR. PMID:26121239

Tree-ring growth patterns and climatic signals along a vertical transect of larch sites in the Simplon and Rhône Valleys (Switzerland)

NASA Astrophysics Data System (ADS)

Riechelmann, Dana F. C.; Esper, Jan

2017-04-01

State-of-the-art millennial long temperature reconstructions from the European Alps integrate wood samples of Larix decidua Mill. from the Lötschental and Simplon regions in Switzerland (Büntgen et al., 2005; 2006). Some of the oldest samples that enable the extension of the time-series back into the first millennium AD are obtained from old buildings in Simplon Village, through the precise location of these samples and the elevation of sampling sites remain unknown. We here evaluate the growth characteristics of larch tree-ring width data along a vertical transect in the Simplon and Rhône valleys. 330 trees from nine sites in 985, 1100, 1400, 1575, 1710, 1712, 1900, 2020, and 2150 m asl have been sampled and analysed for their climate signals. The results indicate a stronger temperature signal in the tree-ring width with increasing elevation. The lower the sites the more a drought signal is imprinted in the ring width data. The intermediate site at 1400 m asl does not show any pronounced climate signal. A comparison of growth patterns of living-tree sites with samples from the historical buildings in Simplon Village (Riechelmann et al., 2013) indicates the construction timber to origin from intermediate to higher elevations. We therefore do not expect strong temperature signal from these timbers. References: Büntgen, U., Esper, J., Frank, D.C., Nicolussi, K., Schmidhalter, M., 2005. A 1052-year tree-ring proxy for Alpine summer temperatures. Climate Dynamics 25: 141-153. Büntgen, U., Frank, D.C., Nievergelt, D., Esper J., 2006. Summer temperature variations in the European Alps, A.D. 755-2004. Journal of Climate 19: 5606-5623. Riechelmann, D.F.C., Schmidhalter, M., Büntgen, U., Esper, J., 2013. Extending a high-elevation larch ring width chronology from the Simplon region in the Swiss Alps over the past millenium. TRACE 11:103-108.

The Multifarious PGPR Serratia marcescens CDP-13 Augments Induced Systemic Resistance and Enhanced Salinity Tolerance of Wheat (Triticum aestivum L.).

PubMed

Singh, Rajnish Prakash; Jha, Prabhat Nath

2016-01-01

The present study demonstrates the plant growth promoting (PGP) potential of a bacterial isolate CDP-13 isolated from 'Capparis decidua' plant, and its ability to protect plants from the deleterious effect of biotic and abiotic stressors. Based on 16S rRNA gene sequence analysis, the isolate was identified as Serratia marcescens. Among the PGP traits, the isolate was found to be positive for ACC deaminase activity, phosphate solubilization, production of siderophore, indole acetic acid production, nitrogen fixation, and ammonia production. CDP-13 showed growth at an increased salt (NaCl) concentration of up to 6%, indicating its potential to survive and associate with plants growing in saline soil. The inoculation of S. marcescens enhanced the growth of wheat plant under salinity stress (150-200 mM). It significantly reduced inhibition of plant growth (15 to 85%) caused by salt stressors. Application of CDP-13 also modulated concentration (20 to 75%) of different osmoprotectants (proline, malondialdehyde, total soluble sugar, total protein content, and indole acetic acid) in plants suggesting its role in enabling plants to tolerate salt stressors. In addition, bacterial inoculation also reduced the disease severity caused by fungal infection, which illustrated its ability to confer induced systemic resistance (ISR) in host plants. Treatment of wheat plants with the test organism caused alteration in anti-oxidative enzymes activities (Superoxide dismutase, Catalase, and Peroxidase) under various salinity levels, and therefore minimizes the salinity-induced oxidative damages to the plants. Colonization efficiency of strain CDP-13 was confirmed by CFU count, epi-fluorescence microscopy, and ERIC-PCR-based DNA fingerprinting approach. Hence, the study indicates that bacterium CDP-13 enhances plant growth, and has potential for the amelioration of salinity stress in wheat plants. Likewise, the results also provide insights into biotechnological approaches to using PGPR as an alternative to chemicals and pesticides.

Soil warming opens the nitrogen cycle at the alpine treeline.

PubMed

Dawes, Melissa A; Schleppi, Patrick; Hättenschwiler, Stephan; Rixen, Christian; Hagedorn, Frank

2017-01-01

Climate warming may alter ecosystem nitrogen (N) cycling by accelerating N transformations in the soil, and changes may be especially pronounced in cold regions characterized by N-poor ecosystems. We investigated N dynamics across the plant-soil continuum during 6 years of experimental soil warming (2007-2012; +4 °C) at a Swiss high-elevation treeline site (Stillberg, Davos; 2180 m a.s.l.) featuring Larix decidua and Pinus uncinata. In the soil, we observed considerable increases in the NH4+ pool size in the first years of warming (by >50%), but this effect declined over time. In contrast, dissolved organic nitrogen (DON) concentrations in soil solutions from the organic layer increased under warming, especially in later years (maximum of +45% in 2012), suggesting enhanced DON leaching from the main rooting zone. Throughout the experimental period, foliar N concentrations showed species-specific but small warming effects, whereas δ 15 N values showed a sustained increase in warmed plots that was consistent for all species analysed. The estimated total plant N pool size at the end of the study was greater (+17%) in warmed plots with Pinus but not in those containing Larix, with responses driven by trees. Irrespective of plot tree species identity, warming led to an enhanced N pool size of Vaccinium dwarf shrubs, no change in that of Empetrum hermaphroditum (dwarf shrub) and forbs, and a reduction in that of grasses, nonvascular plants, and fine roots. In combination, higher foliar δ 15 N values and the transient response in soil inorganic N indicate a persistent increase in plant-available N and greater cumulative plant N uptake in warmer soils. Overall, greater N availability and increased DON concentrations suggest an opening of the N cycle with global warming, which might contribute to growth stimulation of some plant species while simultaneously leading to greater N losses from treeline ecosystems and possibly other cold biomes. © 2016 John Wiley & Sons Ltd.

Influence of biochar on the physical, chemical and retention properties of an amended sandy soil

NASA Astrophysics Data System (ADS)

Baiamonte, Giorgio; De Pasquale, Claudio; Parrino, Francesco; Crescimanno, Giuseppina

2017-04-01

Soil porosity plays an important role in soil-water retention and water availability to crops, potentially affecting both agricultural practices and environmental sustainability. The pore structure controls fluid flow and transport through the soil, as well as the relationship between the properties of individual minerals and plants. Moreover, the anthropogenic pressure on soil properties has produced numerous sites with extensive desertification process close to residential areas. Biochar (biologically derived charcoal) is produced by pyrolysis of biomasses under low oxygen conditions, and it can be applied for recycling organic waste in soils and increase soil fertility, improving soil structure and enhancing soil water storage and soil water movement. Soil application of biochar might have agricultural, environmental and sustainability advantages over the use of organic manures or compost, as it is a porous material with a high inner surface area. The main objectives of the present study were to investigate the possible application of biochar from forest residues, derived from mechanically chipped trunks and large branches of Abies alba M., Larix decidua Mill., Picea excelsa L., Pinus nigra A. and Pinus sylvestris L. pyrolysed at 450 °C for 48h, to improve soil structural and hydraulic properties (achieving a stabilization of soil). Different amount of biochar were added to a desertic sandy soil, and the effect on soil porosity water retention and water available to crops were investigated. The High Energy Moisture Characteristic (HEMC) technique was applied to investigate soil-water retention at high-pressure head levels. The adsorption and desorption isotherms of N2 on external surfaces were also determined in order to investigate micro and macro porosity ratio. Both the described model of studies on adsorption-desorption experiments with the applied isotherms model explain the increasing substrate porosity with a particular attention to the macro and micro porosity, respectively.

Inhibition of IL-6 Signaling Pathway by Curcumin in Uterine Decidual Cells

PubMed Central

Devi, Y. Sangeeta; DeVine, Majesta; DeKuiper, Justin; Ferguson, Susan; Fazleabas, Asgerally T.

2015-01-01

IL-6 is a multifunctional pro-inflammatory cytokine and has been implicated in many gestational disorders including preterm birth. Currently, there are no appropriate therapeutic interventions available to circumvent inflammatory-mediated gestational disorders. Therefore, the goal of this study was to identify a safe and effective pharmacological compound to counterbalance inflammatory responses in the uterus. Curcumin, a naturally-occuring polyphenolic compound, has been widely used in alternative medicine to treat inflammatory diseases. However, the anti-inflammatory effect of curcumin has not been explored in uterine decidual cells, a major source of IL-6. Therefore, we examined the effect of curcumin on IL-6 expression using two types of uterine decidual cells 1) HuF cells, primary human fibroblast cells obtained from the decidua parietalis; 2) UIII cells, a rodent non-transformed decidual cell line. Curcumin treatment completely abrogated the expression of IL-1β-induced IL-6 in these cells. Curcumin also strongly inhibited the expression of gp130, a critical molecule in IL-6 signaling, whereas expression of IL-6R and sIL-6R was not affected. Curcumin also inhibited phosphorylation and nuclear localization of STAT3, a well-known downstream mediator of IL-6 signaling. Furthermore, curcumin attenuated IL-1β-induced IL-6 promoter reporter activity suggesting transcriptional regulation. To further understand whether NF-ҡB is involved in this inhibition, we examined the effect of curcumin on the expression of p50 and p65 subunits of NF-ҡB in decidual cells. Expression of IL-1β-induced p50 mRNA was repressed by curcumin while p65 mRNA was not affected. However, curcumin treatment dramatically inhibited both p50 and p65 protein levels and prevented its nuclear localization. This effect is at least partly mediated through the deactivation of IKK, since IL-1β-induced IKKα/β phosphorylation is decreased upon curcumin treatment. Our results not only revealed molecular mechanisms underlying curcumin action in uterine decidual cells but also suggest that this compound may have therapeutic potential for the prevention of inflammation-mediated preterm birth and other gestational disorders. PMID:25961579

Similar variation in carbon storage between deciduous and evergreen treeline species across elevational gradients

PubMed Central

Fajardo, Alex; Piper, Frida I.; Hoch, Günter

2013-01-01

Background and Aims The most plausible explanation for treeline formation so far is provided by the growth limitation hypothesis (GLH), which proposes that carbon sinks are more restricted by low temperatures than by carbon sources. Evidence supporting the GLH has been strong in evergreen, but less and weaker in deciduous treeline species. Here a test is made of the GLH in deciduous–evergreen mixed species forests across elevational gradients, with the hypothesis that deciduous treeline species show a different carbon storage trend from that shown by evergreen species across elevations. Methods Tree growth and concentrations of non-structural carbohydrates (NSCs) in foliage, branch sapwood and stem sapwood tissues were measured at four elevations in six deciduous–evergreen treeline ecotones (including treeline) in the southern Andes of Chile (40°S, Nothofagus pumilio and Nothofagus betuloides; 46°S, Nothofagus pumilio and Pinus sylvestris) and in the Swiss Alps (46°N, Larix decidua and Pinus cembra). Key Results Tree growth (basal area increment) decreased with elevation for all species. Regardless of foliar habit, NSCs did not deplete across elevations, indicating no shortage of carbon storage in any of the investigated tissues. Rather, NSCs increased significantly with elevation in leaves (P < 0·001) and branch sapwood (P = 0·012) tissues. Deciduous species showed significantly higher NSCs than evergreens for all tissues; on average, the former had 11 % (leaves), 158 % (branch) and 103 % (sapwood) significantly (P < 0·001) higher NSCs than the latter. Finally, deciduous species had higher NSC (particularly starch) increases with elevation than evergreens for stem sapwood, but the opposite was true for leaves and branch sapwood. Conclusions Considering the observed decrease in tree growth and increase in NSCs with elevation, it is concluded that both deciduous and evergreen treeline species are sink limited when faced with decreasing temperatures. Despite the overall higher requirements of deciduous tree species for carbon storage, no indication was found of carbon limitation in deciduous species in the alpine treeline ecotone. PMID:23788748

Factors driving mortality and growth at treeline: a 30-year experiment of 92 000 conifers.

PubMed

Barbeito, Ignacio; Dawes, Melissa A; Rixen, Christian; Senn, Josef; Bebi, Peter

2012-02-01

Understanding the interplay between environmental factors contributing to treeline formation and how these factors influence different life stages remains a major research challenge. We used an afforestation experiment including 92 000 trees to investigate the spatial and temporal dynamics of tree mortality and growth at treeline in the Swiss Alps. Seedlings of three high-elevation conifer species (Larix decidua, Pinus mugo ssp. uncinata, and Pinus cembra) were systematically planted along an altitudinal gradient at and above the current treeline (2075 to 2230 m above sea level [a.s.l.]) in 1975 and closely monitored during the following 30 years. We used decision-tree models and generalized additive models to identify patterns in mortality and growth along gradients in elevation, snow duration, wind speed, and solar radiation, and to quantify interactions between the different variables. For all three species, snowmelt date was always the most important environmental factor influencing mortality, and elevation was always the most important factor for growth over the entire period studied. Individuals of all species survived at the highest point of the afforestation for more than 30 years, although mortality was greater above 2160 m a.s.l., 50-100 m above the current treeline. Optimal conditions for height growth differed from those for survival in all three species: early snowmelt (ca. day of year 125-140 [where day 1 is 1 January]) yielded lowest mortality rates, but relatively later snowmelt (ca. day 145-150) yielded highest growth rates. Although snowmelt and elevation were important throughout all life stages of the trees, the importance of radiation decreased over time and that of wind speed increased. Our findings provide experimental evidence that tree survival and height growth require different environmental conditions and that even small changes in the duration of snow cover, in addition to changes in temperature, can strongly impact tree survival and growth patterns at treeline. Further, our results show that the relative importance of different environmental variables for tree seedlings changes during the juvenile phase as they grow taller.

Impact of shelterbelts of different age on the content of nitrates and phosphates in ground water

NASA Astrophysics Data System (ADS)

Jaskulska, Renata; Wojciech Szajdak, Lech

2010-05-01

The investigations were carried out in the Agroecological Landscape Park situated 40 km South-West of Poznań in the upper Obra River watershed, Poland. The arable land constitutes 70%, shelterbelts and small afforestations about 14% and meadows and pastures about 12%. Shelterbelts belong to very efficient biogeochemical barriers. They decrease the migration of chemical compounds between ecosystems. The direction of ground water flow was from the adjoining cultivated field towards shelterbelts. Two shelterbelts of different humus guantity in surface layer soils were investigated. The age and species composition of plant was taken under consideration. The first one is 160-year-old shelterbelt, where predominant species is Robinia pseudoacacia, Quercus rober and Alnus glutinosa and is characterized by a well-developed humus level. The other one is 14-year-old shelterbelt. It includes 13 species of trees (Quercus petrea, Larix deciduas, Pinus silvestri, Populus nigra, Sorbus aucuparia) and reveals a small amount of humus. The soils are minerals, grey-brown podzolic in surface layer soils compound from light loamy sands and weakly loamy sands. The contents of N-NO3-, P-PO4-3, were investigated in the ground water under shelterbelts and adjoining cultivated fields. In addition, cationic sorptive capacity, specific surface areas, TOC were determined in soils. The smallest concentrations of nitrates (3.35 mg×l-1) and phosphates (0.02 mg×l-1) were observed in ground water under the 160-year-old shelterbelt. The physicochemical properties of soils under 160-year-old shelterbelt: specific surface areas (20.3 m2×g-1), cationic sorptive capacity (24.8 cmol(+)×kg-1), TOC (4.3%) was higher than in 14-year-old shelterbelt and in adjoining cultivated fields. The results revealed, that the 160-year-old shelterbelt characterizing developed humus more effectively than 14-year-old shelterbelt decreases the amounts of chemical compounds in ground water and sufficiently fulfils the function such as biogeochemical barrier in agricultural landscape. This work was supported by a grant No. N N305 229535 founded by Polish Ministry of Education.

Regulation of NucB2/Nesfatin-1 throughout rat pregnancy.

PubMed

Garcés, María F; Poveda, Natalia E; Sanchez, Elizabeth; Sánchez, Ángel Y; Bravo, Susana B; Vázquez, María J; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E

2014-06-22

Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic role during pregnancy and fetal development and its energy balance mediating role should be studied in various physiological and pathological conditions throughout gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

Human Chorionic Gonadotropin: Unknown about Known.

PubMed

Borisova, M A; Moiseenko, D Yu; Smirnova, O V

2017-01-01

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

The Imprint of Extreme Climate Events in Century-Long Time Series of Wood Anatomical Traits in High-Elevation Conifers

PubMed Central

Carrer, Marco; Brunetti, Michele; Castagneri, Daniele

2016-01-01

Extreme climate events are of key importance for forest ecosystems. However, both the inherent infrequency, stochasticity and multiplicity of extreme climate events, and the array of biological responses, challenges investigations. To cope with the long life cycle of trees and the paucity of the extreme events themselves, our inferences should be based on long-term observations. In this context, tree rings and the related xylem anatomical traits represent promising sources of information, due to the wide time perspective and quality of the information they can provide. Here we test, on two high-elevation conifers (Larix decidua and Picea abies sampled at 2100 m a.s.l. in the Eastern Alps), the associations among temperature extremes during the growing season and xylem anatomical traits, specifically the number of cells per ring (CN), cell wall thickness (CWT), and cell diameter (CD). To better track the effect of extreme events over the growing season, tree rings were partitioned in 10 sectors. Climate variability has been reconstructed, for 1800–2011 at monthly resolution and for 1926–2011 at daily resolution, by exploiting the excellent availability of very long and high quality instrumental records available for the surrounding area, and taking into account the relationship between meteorological variables and site topographical settings. Summer temperature influenced anatomical traits of both species, and tree-ring anatomical profiles resulted as being associated to temperature extremes. Most of the extreme values in anatomical traits occurred with warm (positive extremes) or cold (negative) conditions. However, 0–34% of occurrences did not match a temperature extreme event. Specifically, CWT and CN extremes were more clearly associated to climate than CD, which presented a bias to track cold extremes. Dendroanatomical analysis, coupled to high-quality daily-resolved climate records, seems a promising approach to study the effects of extreme events on trees, but further investigations are needed to improve our comprehension of the critical role of such elusive events in forest ecosystems. PMID:27242880

Lower Circulating Folate Induced by a Fidgetin Intronic Variant Is Associated With Reduced Congenital Heart Disease Susceptibility.

PubMed

Wang, Dan; Wang, Feng; Shi, Kai-Hu; Tao, Hui; Li, Yang; Zhao, Rui; Lu, Han; Duan, Wenyuan; Qiao, Bin; Zhao, Shi-Min; Wang, Hongyan; Zhao, Jian-Yuan

2017-05-02

Folate deficiency is an independent risk factor for congenital heart disease (CHD); however, the maternal plasma folate level is paradoxically not a good diagnostic marker. Genome-wide surveys have identified variants of nonfolate metabolic genes associated with the plasma folate level, suggesting that these genetic polymorphisms are potential risk factors for CHD. To examine the effects of folate concentration-related variations on CHD risk in the Han Chinese population, we performed 3 independent case-control studies including a total of 1489 patients with CHD and 1745 control subjects. The expression of the Fidgetin (FIGN) was detected in human cardiovascular and decidua tissue specimens with quantitative real-time polymerase chain reaction and Western blotting. The molecular mechanisms were investigated by luciferase reporter assays, surface plasmon resonance, and chromatin immunoprecipitation. FIGN-interacting proteins were confirmed by tandem affinity purification and coimmunoprecipitation. Proteasome activity and metabolite concentrations in the folate pathway were quantified with a commercial proteasome activity assay and immunoassays, respectively. The +94762G>C (rs2119289) variant in intron 4 of the FIGN gene was associated with significant reduction in CHD susceptibility ( P =5.1×10 -14 for the allele, P =8.5×10 --13 for the genotype). Analysis of combined samples indicated that CHD risks in individuals carrying heterozygous (GC) or homozygous (CC) genotypes were reduced by 44% (odds ratio [OR]=0.56; 95% confidence interval [CI]=0.47-0.67) and 66% (OR=0.34; 95% CI=0.23-0.50), respectively, compared with those with the major GG genotype. Minor C allele carriers who had decreased plasma folate levels exhibited significantly increased FIGN expression because the transcription suppressor CREB1 did not bind the alternative promoter of FIGN isoform X3. Mechanistically, increased FIGN expression led to the accumulation of both reduced folate carrier 1 and dihydrofolate reductase via inhibition of their proteasomal degradation, which promoted folate absorption and metabolism. We report a previously undocumented finding that decreased circulating folate levels induced by increased folate transmembrane transport and utilization, as determined by the FIGN intronic variant, serves as a protective mechanism against CHD. Our results may explain why circulating folate levels do not have a good diagnostic value. © 2017 American Heart Association, Inc.

Placenta accreta spectrum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging.

PubMed

Jauniaux, Eric; Collins, Sally; Burton, Graham J

2018-01-01

Placenta accreta spectrum is a complex obstetric complication associated with high maternal morbidity. It is a relatively new disorder of placentation, and is the consequence of damage to the endometrium-myometrial interface of the uterine wall. When first described 80 years ago, it mainly occurred after manual removal of the placenta, uterine curettage, or endometritis. Superficial damage leads primarily to an abnormally adherent placenta, and is diagnosed as the complete or partial absence of the decidua on histology. Today, the main cause of placenta accreta spectrum is uterine surgery and, in particular, uterine scar secondary to cesarean delivery. In the absence of endometrial reepithelialization of the scar area the trophoblast and villous tissue can invade deeply within the myometrium, including its circulation, and reach the surrounding pelvic organs. The cellular changes in the trophoblast observed in placenta accreta spectrum are probably secondary to the unusual myometrial environment in which it develops, and not a primary defect of trophoblast biology leading to excessive invasion of the myometrium. Placenta accreta spectrum was separated by pathologists into 3 categories: placenta creta when the villi simply adhere to the myometrium, placenta increta when the villi invade the myometrium, and placenta percreta where the villi invade the full thickness of the myometrium. Several prenatal ultrasound signs of placenta accreta spectrum were reported over the last 35 years, principally the disappearance of the normal uteroplacental interface (clear zone), extreme thinning of the underlying myometrium, and vascular changes within the placenta (lacunae) and placental bed (hypervascularity). The pathophysiological basis of these signs is due to permanent damage of the uterine wall as far as the serosa, with placental tissue reaching the deep uterine circulation. Adherent and invasive placentation may coexist in the same placental bed and evolve with advancing gestation. This may explain why no single, or set combination of, ultrasound sign(s) was found to be specific for the depth of abnormal placentation, and accurate for the differential diagnosis between adherent and invasive placentation. Correlation of pathological and clinical findings with prenatal imaging is essential to improve screening, diagnosis, and management of placenta accreta spectrum, and standardized protocols need to be developed. Copyright © 2017 Elsevier Inc. All rights reserved.

Chorion Mesenchymal Stem Cells Show Superior Differentiation, Immunosuppressive, and Angiogenic Potentials in Comparison With Haploidentical Maternal Placental Cells

PubMed Central

González, Paz L.; Carvajal, Catalina; Cuenca, Jimena; Alcayaga-Miranda, Francisca; Figueroa, Fernando E.; Bartolucci, Jorge; Salazar-Aravena, Lorena

2015-01-01

Mesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine. Significance This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine. PMID:26273064

Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

PubMed Central

2010-01-01

Background Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1), play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc) family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium. Methods A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1) and prolactin (PRL) confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p < 0.05, p < 0.02 and p < 0.01 and one way post-hoc ANOVA test with p < 0.05 as cut-offs for statistical significance. Results The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation. Conclusions Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an important role as a co-receptor and storage factor for many cytokines and angiogenic factors during decidualization and implantation period, supporting proper implantation and angiogenesis by regulation of chemokine and angiogenic factor secretion in favour of the implanting embryo. PMID:21044331

Effects of different tree species on soil organic matter composition, decomposition rates and temperature sensitivities in boreal forest

NASA Astrophysics Data System (ADS)

Segura, Javier; Nilsson, Mats B.; Erhagen, Björn; Sparrman, Tobias; Ilstedt, Ulrik; Schleucher, Jürgen; Öquist, Mats

2017-04-01

High-latitude ecosystems store a large proportion of the global soil organic matter (SOM) and its mineralization constitutes a major carbon flux to the atmosphere. It has been suggested that different tree species can significantly influence organo-chemical composition of SOM, and rate and temperature sensitivity of SOM decomposition. In this study we used surface soil samples (top 5 cm) from a field experiment where five different tree species (Pinus silvestrys L, Picea abies (L.) H. Karst., Larix decidua Mill., Betula pendula Roth, and Pinus contorta Douglas) were planted on a grass meadow in a randomized block design (n=3) ca. 40 years ago. The samples were incubated at 4, 9, 14, and 19 °C at a soil water potential of -25 kPa (previously determined as optimal water content for decomposition). CO2 production rates were measured hourly for 13 days. CO2 production rates were consequently lowest in the control plots and increased in the order Meadow< Contorta < Betula < Larix < Pinus < Picea. The values ranged between 0.03-0.1, 0.06-0.154, 0.1-0.24 and 0.13-0.36 mg CO2 g-1 OM (dw) h-1 at 4, 9, 14 and 19°C respectively. The temperature response of CO2 production corresponded to Q10s of 2.22 (±0.11), 2.22(±0.15), 2.66 (±0.18), 2.09 (±0.33), 2.38 (±0.31) and 2.31 (±0.09) for meadow, contorta, betula, larix, pinus and picea respectively. Only betula resulted in significantly higher Q10s as compared to the control plots, picea, contorta and larix treatments. These differences in tree species effects on SOM decomposition and its temperature sensitivity will be further discussed in relation to the organo-chemical composition of SOM as determined by pyrolysis gas chromatography-mass spectrometry (Py-GC-MS) and nuclear magnetic resonance spectroscopy (NMR) techniques. We conclude that the temperature response of SOM decomposition rates is likely coupled to tree species composition and may have important implications for soil C dynamics. This finding can have important implications for both the understanding of forest ecosystem carbon balances in high latitude ecosystems and also the selection of different tree species in forest management schemes.

The role of vitamin D in impaired fertility treatment.

PubMed

Grzechocinska, Barbara; Dabrowski, Filip A; Cyganek, Anna; Wielgos, Miroslaw

2013-01-01

Vitamin D is currently in the scope of research in many fields of medicine. Despite that its influence on health remains uncertain. This paper presents the review of the publications concerning the role of calciferol in reproduction processes and its significance in infertility therapy covering topics of polycystic ovary syndrome, endometriosis infertility, myoma infertility, male infertility, premature ovary failure and in vitro fertilization techniques. The results of latest research articles in those fields has been discussed and summarized. The deficiency of vitamin defined as the concentration of 25-hydroxycalciferol <20 ng/ml is frequently noted in patients of fertility clinics. Serum vitamin D concentration in healthy women is higher comparing to PCOS patients. The supplementation with vitamin D should be applied in the schemes of PCOS treatment both due to an improved insulin resistance and the results of infertility treatment. The explanation of vitamin D activity mechanism in patients with PCOS requires further research. Vitamin D have direct effect on AMH production, and thus increase longer maintenance of ovarian reserve in the patients with its higher concentration. The occurrence of uterine myomas in the group with vitamin D deficiency was evaluated as much higher comparing to controls. On the other hand it is supposed that high concentration of calciferol may be related to an impaired elimination of endometrial cells passing to peritoneal cavity via ovarian reflux causing endometriosis. In male infertility both low (<20 ng/ml) and high (>50 ng/ml) concentration of vitamin D in serum negatively affects spermatozoa number per ml of semen, their progressive movement and morphology. Significant differences as a response on ovulation stimulation, number and quality of embryos depending on vitamin D concentration were not observed in none of the analyzed papers concerning the role of vitamin D in in vitro fertilization (IVF). Better results in patients without calciferol insufficiency are explained by reports about high concentration of vitamin D and its metabolites in human in decidua collected in the 1st trimester of pregnancy which suggests its contribution in proper implantation and local immunological preference of the embryo. It is accepted that the treatment requires vitamin D concentration below 20 ng/ml (up to 50 nmol/l), especially in obese women, these with insulin resistance and small ovarian reserve and in men with oligo- and asthenozoospermia.

Abortion.

PubMed

Cattanach, J F

1979-03-10

As abortion is the destruction of individual human life, if an abortion is to be performed at all there must be grave reasons for it which should necessitate complete documentation. Surely human life should be given that respect at least. Legislation should oblige any doctor intending to perform an induced abortion to list the indications which in his or her opinion make that abortion lawful. A signed copy of that opinion should be sent to an official authority of notification. This authority could be developed along the lines of the Neonatal Deaths Committees with authority to check any such notification through consultant tribunals, similar to those existing in New Zealand, which would have access to the patient. The simplest way to ensure that an induced abortion of a viable pregnancy has not occurred at any curettage is to pass legislation which would make it mandatory that all tissue obtained at all uterine curettages or evacuations be sent for histopathological examination. Should the pathologist find evidence of an induced abortion or hysterotomy a copy of the pathology report would then be sent to the official committee. The usual copies would be sent to the doctor and hospital concerned. All such procedures would have to be carried out at registered hospitals. All medical staff members and nurses would have access to such reports. It would be a grave offence for the doctor, pathologist or hospital not to comply with the above procedure. The official committee would have the power to demand samples of tissue for examination by its own consultant pathologist, and to investigate irregularities in the above procedure. Pathologists concur that induced abortion can be accurately differentiated from other types of abortion, as there is an infiltration of polymorphs into the decidua within about three hours of fetal death in incomplete abortion, and there are other features such as hyalinization of placental villi. Apparently, these differences are so basic that a Medlars search of references appears to indicate that no formal research has been carried out. A pathologist with special expertise in uterine histopathology, Dr. Allan Bodie, agreed to conduct formal research to establish that this differentiation is accurate, and, on the basis of a preliminary series which he intends publishing soon, he has confirmed this (personal communciation). If procedures were to operate this way the law can be seen to be upheld, some respect given to prenatal human life, and valid research and statistics gained.

Genetic selection of embryos that later develop the metabolic syndrome.

PubMed

Edwards, M J

2012-05-01

THE BARKER HYPOTHESIS: Is an excellent explanation of the process where human and animal foetuses exposed to malnutrition, either by maternal malnutrition or placental insufficiency, are metabolically programmed, with selective stunting of cell differentiation and organ growth. With the postnatal excess of nutrition observed in developed countries, this irreversible programming causes metabolic syndrome, including obesity, type 2 diabetes, and hypertension. Metabolic programming involves epigenetic changes including imprinting which might be transmitted through more than one generation rather than being completely re-set or erased during reproduction. The Barker hypothesis was supported by epidemiological data that recognised no excess fetal or postnatal mortality when pregnant women were starved during the Dutch famine in World War II. This argued against the "thrifty genotype" theory introduced in 1962, which proposed that starvation selected against members of the population with less "thrifty" genes, but the survivors who had "thrifty" genes developed metabolic syndrome if they were subsequently over-nourished. EMBRYONIC/FETAL SELECTION: Embryos or early foetuses could be selected very early in pregnancy on the basis of their genotype, by maternal malnutrition, hypertension, obesity or other causes of placental insufficiency. The genotype that allows embryos, or cells within them, to survive a less hospitable environment in the decidua after implantation might contribute to the later development of metabolic syndrome. This article hypothesises that an adverse intrauterine environment, caused by maternal malnutrition or placental insufficiency, kills a proportion of embryos and selects a surviving population of early embryos whose growth in utero is retarded by their genotype, their environment or a combination of both. The metabolic syndrome follows if the offspring is over-nourished later in life. The embryonic selection hypothesis presented here could be tested by using single nucleotide polymorphism (SNP) microarrays to study adults who had a history of intrauterine growth retardation (IUGR) and subsequent metabolic syndrome. Their SNP array could be compared with their parents and unaffected unrelated or related controls. If there were no selection based on a "thrifty genotype", all parental sequences would be expected to appear in their surviving children, whether or not they had IUGR or developed metabolic syndrome. SNP sequences present in parents or controls but missing from adult offspring with metabolic syndrome who had IUGR, could be associated with or linked to genes that influence susceptibility to metabolic syndrome. This hypothesis proposes that missing genotypes would be lost if the embryos that inherited them died very early in pregnancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of climate warming-induced increase in drought stress on successional dynamic of a coniferous forest within a dry inner Alpine environment

NASA Astrophysics Data System (ADS)

Schuster, R.; Zeisler, B.; Oberhuber, W.

2012-04-01

Climate sensitivity of tree growth will effect the development of forest ecosystems under a warmer and drier climate by changing species composition and inducing shifts in forest distribution. We applied dendroclimatological techniques to determine impact of climate warming on radial stem growth of three native and widespread coniferous tree species of the central Austrian Alps (Norway spruce, Picea abies; European larch, Larix decidua; Scots pine, Pinus sylvestris), which grow intermixed at dry-mesic sites within a dry inner Alpine environment (750 m a.s.l., Tyrol, Austria). Time series of annual increments were developed from > 250 saplings and mature trees. Radial growth response to recent climate warming was explored by means of moving response functions (MRF) and evaluation of trends in basal area increment (BAI) for the period 1911 - 2009. Climate-growth relationships revealed significant differences among species in response to water availability. While precipitation in May - June favoured radial growth of spruce and larch, Scots pine growth mainly depended on April - May precipitation. Spruce growth was most sensitive to May - June temperature (inverse relationship). Although MRF coefficients indicated increasing drought sensitivity of all species, which is most likely related to intensified belowground competition for scarce water with increasing stand density and higher evapotranspiration rates due to climate warming, recent BAI trends strikingly differed among species. While BAI of larch was distinctly declining, spruce showed steadily increasing BAI and quite constant BAI was maintained in drought adapted Scots pine, although at lowest level of all species. Furthermore, more favourable growing conditions of spruce in recent decades are indicated by scattered natural regeneration and higher growth rates of younger trees during first decades of their lifespan. Because human interference and wildlife stock is negligible within the study area, results suggest a competitive advantage of shade-tolerant and shallow-rooted late successional spruce over early successional species, whereby the spruce`s competitive strength is most likely related to synergistic effects of shade-tolerance and efficient uptake of small rainfall events by fine roots distributed primarily in upper soil layers. On the other hand, strikingly decreasing trend in BAI of larch is suggested to be due to negative influence of climate warming on tree water status. We conclude that climate warming-induced increase in drought sensitivity changed competitive strength of co-occurring conifers due to differences in inherent adaptive capacity at a drought-prone inner Alpine site.

Persistence of decidual NK cells and KIR genotypes in healthy pregnant and preeclamptic women: a case-control study in the third trimester of gestation

PubMed Central

2011-01-01

Background Natural Killer (NK) cells are the most abundant lymphocytes in the decidua during early gestation. The interactions of NK cells with the extravillous cytotrophoblast have been associated with a normal spiral artery remodeling process, an essential event for a successful pregnancy. Recent data indicate that alterations in the amount of decidual NK (dNK) cells contribute to the development of preeclampsia (PE). Moreover, genetic studies suggest that Killer Immunoglobulin-like Receptors (KIR) expressed in dNK cells influence the susceptibility to PE. Although dNK cells have been well characterized during early pregnancy, they have been scarcely studied in the third trimester of gestation. The aim of this work was to characterize dNK cells at the last trimester of gestation and to analyze the KIR genotype of healthy and PE women. Methods Decidual samples were obtained during Caesarean section from control (n = 10) and PE (n = 9) women. Flow cytometric analysis of CD3, CD56, CD16 and CD9 was used to characterize and quantify dNK cells in both groups. Cell surface markers from decidual leukocytes were compared with PBMC from healthy donors. KIR genotyping was performed in genomic DNA (control, n = 86; PE, n = 90) using PCR-SSP. Results The results indicate that dNK cells persist throughout pregnancy. They represented 20% of total leukocytes in control and PE groups, and they expressed the same cell surface markers (CD3-, CD56+, CD16- and CD9+) as dNK in the first trimester of gestation. There were no significant differences in the percentage of dNK cells between control and PE groups. The analysis of KIR gene frequencies and genotypes was not statistically different between control and PE groups. The ratio of activating to inhibitory genes indicated that the overall inhibitory balance (0.2-0.5) was more frequent in the PE group (control, 31.3% vs PE, 45.5%), and the activating balance (0.6-1.1) was more frequent in the control group (control, 68.6% vs PE, 54.4%). However this difference was not significant. Conclusion We demonstrated the persistence of dNK cells in PE and control women at the third trimester of pregnancy; these dNK cells had a similar phenotype to those found during early pregnancy. The predominance of a KIR inhibitory balance in the PE group could be associated to the physiopathology of PE. PMID:21247496

PreImplantation factor (PIF*) promotes embryotrophic and neuroprotective decidual genes: effect negated by epidermal growth factor.

PubMed

Duzyj, Christina M; Paidas, Michael J; Jebailey, Lellean; Huang, Jing Shun; Barnea, Eytan R

2014-01-01

Intimate embryo-maternal interaction is paramount for pregnancy success post-implantation. The embryo follows a specific developmental timeline starting with neural system, dependent on endogenous and decidual factors. Beyond altered genetics/epigenetics, post-natal diseases may initiate at prenatal/neonatal, post-natal period, or through a continuum. Preimplantation factor (PIF) secreted by viable embryos promotes implantation and trophoblast invasion. Synthetic PIF reverses neuroinflammation in non-pregnant models. PIF targets embryo proteins that protect against oxidative stress and protein misfolding. We report of PIF's embryotrophic role and potential to prevent developmental disorders by regulating uterine milieu at implantation and first trimester. PIF's effect on human implantation (human endometrial stromal cells (HESC)) and first-trimester decidua cultures (FTDC) was examined, by global gene expression (Affymetrix), disease-biomarkers ranking (GeneGo), neuro-specific genes (Ingenuity) and proteins (mass-spectrometry). PIF co-cultured epidermal growth factor (EGF) in both HESC and FTDC (Affymetrix) was evaluated. In HESC, PIF promotes neural differentiation and transmission genes (TLX2, EPHA10) while inhibiting retinoic acid receptor gene, which arrests growth. PIF promotes axon guidance and downregulates EGF-dependent neuroregulin signaling. In FTDC, PIF promotes bone morphogenetic protein pathway (SMAD1, 53-fold) and axonal guidance genes (EPH5) while inhibiting PPP2R2C, negative cell-growth regulator, involved in Alzheimer's and amyotrophic lateral sclerosis. In HESC, PIF affects angiotensin via beta-arrestin, transforming growth factor-beta (TGF-β), notch, BMP, and wingless-int (WNT) signaling pathways that promote neurogenesis involved in childhood neurodevelopmental diseases-autism and also affected epithelial-mesenchymal transition involved in neuromuscular disorders. In FTDC, PIF upregulates neural development and hormone signaling, while downregulating genes protecting against xenobiotic response leading to connective tissue disorders. In both HESC and FTDC, PIF affects neural development and transmission pathways. In HESC interactome, PIF promotes FUS gene, which controls genome integrity, while in FTDC, PIF upregulates STAT3 critical transcription signal. EGF abolished PIF's effect on HESC, decreasing metalloproteinase and prolactin receptor genes, thereby interfering with decidualization, while in FTDC, EGF co-cultured with PIF reduced ZHX2, gene that regulates neural AFP secretion. PIF promotes decidual trophic genes and proteins to regulate neural development. By regulating the uterine milieu, PIF may decrease embryo vulnerability to post-natal neurodevelopmental disorders. Examination of PIF-based intervention strategies used during embryogenesis to improve pregnancy prognosis and reduce post-natal vulnerability is clearly in order.

Climatic interpretation of tree-ring methoxyl d2H time-series from a central alpine larch forest

NASA Astrophysics Data System (ADS)

Riechelmann, Dana F. C.; Greule, Markus; Siegwolf, Rolf T. W.; Esper, Jan; Keppler, Frank

2017-04-01

We measured stable hydrogen isotope ratios of lignin methoxyl groups (d2HLM) in high elevation larch trees (Larix decidua Mill.) from the Simplon Valley in southern Switzerland. Thirty-seven larch trees were sampled and five individuals analysed for their d2HLM values at annual (1971-2009) and pentadal resolution (1746-2009). Testing the climate response of the d2HLM series, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation and weaker but negative correlation with June/July temperature. In addition, a negative correlation with June-August d2H in precipitation of the nearby GNIP station in Locarno is observed. The pentadally resolved d2HLM series show no significant correlation to climate parameters. The positive correlation of the annually resolved data to summer precipitation is uncommon to d2H measurements from tree-rings (Feakins et al., 2013; Helle and Schleser, 2004; McCarroll and Loader, 2004; Mischel et al., 2015; White et al., 1994). However, we explain the positive association with warm season hydroclimate as follows: methoxyl groups of lignin are directly formed from tissues in the xylem water. More precipitation during June and July, which are on average relatively dry month, results in higher d2H values of the xylem water and therefore, higher d2H value in the lignin methoxyl groups. Therefore, we suggest that d2HLM values of high elevation larch trees might likely serve as a summer precipitation proxy. References: Feakins, S.J., Ellsworth, P.V., Sternberg, L.d.S.L., 2013. Lignin methoxyl hydrogen isotope rations in a coastal ecosystem. Geochimica et Cosmochimica Acta, 121: 54-66. Helle, G., Schleser, G.H., 2004. Interpreting Climate Proxies from Tree-rings. In: Fischer, H., Floeser, G., Kumke, T., Lohmann, G., Miller, H., Negendank, J.F.W., et al., editors. The Climate in Historical Times. Springer Berlin Heidelberg, pp. 129-148. McCarroll, D., Loader, N.J., 2004. Stable isotopes in tree rings. Quaternary Science Reviews, 23: 771-801. Mischel, M., Esper, J., Keppler, F., Greule, M., Werner, W., 2015. d2H, d13C and d18O from whole wood, a-cellulose and lignin methoxyl groups in Pinus sylvestris: a multi-parameter approach. Isotopes in Environmental and Health Studies, 1-16. White, J.W.C., Lawrence, J.R., Broecker, W.S., 1994. Modeling and interpreting D/H ratios in tree rings: A test case of white pine in the northeastern United States. Geochimica et Cosmochimica Acta, 58: 851-862.

Environmental and climatic conditions at a potential Glacial refugial site of tree species near the Southern Alpine glaciers. New insights from multiproxy sedimentary studies at Lago della Costa (Euganean Hills, Northeastern Italy)

NASA Astrophysics Data System (ADS)

Kaltenrieder, Petra; Belis, Claudio A.; Hofstetter, Simone; Ammann, Brigitta; Ravazzi, Cesare; Tinner, Willy

2009-12-01

It has been hypothesized that refugia of thermophilous tree species were located in Northern Italy very close to the Alps, though, this hypothesis has yet to be tested thoroughly. In contrast to Central and Southern Italy with its relative wealth of data, only a few fragmentary records are currently available from Northern Italy for the last Glacial (Würm, Weichselian). Our new study site Lago della Costa lies adjacent to the catchment of the megafans of the Alpine forelands and the braided rivers of the Northeastern Po Plain that have so far inhibited the recovery of continuous Glacial and Late-Glacial records. We analyze pollen, plant macrofossils, charcoal and ostracods to reconstruct the vegetation, fire and lake history for the period 33,000-16,000 cal. BP. We compare our data with Glacial records from Southern Europe to discuss similarities and dissimilarities between these potential refugial areas. A comparison with independent paleoclimatic proxies allows to assess potential linkages between environmental and climatic variability. New macrofossil and pollen data at Lago della Costa unambiguously document the local persistence of boreal tree taxa such as Larix decidua and Betula tree species around the study site during the last Glacial. The regular occurrence of pollen of temperate trees in the organic lake sediments (fine-detritus calcareous gyttja) suggests that temperate taxa such as Corylus avellana, Quercus deciduous, Tilia, Ulmus, Fraxinus excelsior, Carpinus, Abies alba and Fagus sylvatica, most likely survived the Last Glacial Maximum (LGM) at favorable sites in the Euganean Hills. The percentage values of temperate trees are comparable with those from Southern Europe (e.g. Monticchio in Southern Italy). We conclude that the Euganean Hills were one of the northernmost refugial areas of temperate taxa in Europe. However, the relative and absolute abundances of pollen of temperate trees are highly variable. Pollen-inferred declines of temperate tree communities (e.g. Quercetum mixtum) and low ostracod-inferred water levels at Lago della Costa correspond to the cold Heinrich events H-2 (LGM; 23,000-19,000 cal. BP) and H-3 (around 28,000 cal. BP), as recorded in the marine sediments of the North Atlantic. Similar patterns of significant temperate tree population collapses during cold Heinrich events are recorded at southern Mediterranean sites (e.g. Monticchio and the Alboran Sea). These findings suggest close linkages between Northern Atlantic and South-Central European climates during the past Glacial.

PreImplantation factor (PIF*) promotes embryotrophic and neuroprotective decidual genes: effect negated by epidermal growth factor

PubMed Central

2014-01-01

Background Intimate embryo-maternal interaction is paramount for pregnancy success post-implantation. The embryo follows a specific developmental timeline starting with neural system, dependent on endogenous and decidual factors. Beyond altered genetics/epigenetics, post-natal diseases may initiate at prenatal/neonatal, post-natal period, or through a continuum. Preimplantation factor (PIF) secreted by viable embryos promotes implantation and trophoblast invasion. Synthetic PIF reverses neuroinflammation in non-pregnant models. PIF targets embryo proteins that protect against oxidative stress and protein misfolding. We report of PIF’s embryotrophic role and potential to prevent developmental disorders by regulating uterine milieu at implantation and first trimester. Methods PIF’s effect on human implantation (human endometrial stromal cells (HESC)) and first-trimester decidua cultures (FTDC) was examined, by global gene expression (Affymetrix), disease-biomarkers ranking (GeneGo), neuro-specific genes (Ingenuity) and proteins (mass-spectrometry). PIF co-cultured epidermal growth factor (EGF) in both HESC and FTDC (Affymetrix) was evaluated. Results In HESC, PIF promotes neural differentiation and transmission genes (TLX2, EPHA10) while inhibiting retinoic acid receptor gene, which arrests growth. PIF promotes axon guidance and downregulates EGF-dependent neuroregulin signaling. In FTDC, PIF promotes bone morphogenetic protein pathway (SMAD1, 53-fold) and axonal guidance genes (EPH5) while inhibiting PPP2R2C, negative cell-growth regulator, involved in Alzheimer’s and amyotrophic lateral sclerosis. In HESC, PIF affects angiotensin via beta-arrestin, transforming growth factor-beta (TGF-β), notch, BMP, and wingless-int (WNT) signaling pathways that promote neurogenesis involved in childhood neurodevelopmental diseases—autism and also affected epithelial-mesenchymal transition involved in neuromuscular disorders. In FTDC, PIF upregulates neural development and hormone signaling, while downregulating genes protecting against xenobiotic response leading to connective tissue disorders. In both HESC and FTDC, PIF affects neural development and transmission pathways. In HESC interactome, PIF promotes FUS gene, which controls genome integrity, while in FTDC, PIF upregulates STAT3 critical transcription signal. EGF abolished PIF’s effect on HESC, decreasing metalloproteinase and prolactin receptor genes, thereby interfering with decidualization, while in FTDC, EGF co-cultured with PIF reduced ZHX2, gene that regulates neural AFP secretion. Conclusions PIF promotes decidual trophic genes and proteins to regulate neural development. By regulating the uterine milieu, PIF may decrease embryo vulnerability to post-natal neurodevelopmental disorders. Examination of PIF-based intervention strategies used during embryogenesis to improve pregnancy prognosis and reduce post-natal vulnerability is clearly in order. PMID:26085845

Changes in fungal community composition in response to experimental soil warming at the alpine treeline

NASA Astrophysics Data System (ADS)

Solly, Emily; Lindahl, Bjorn; Dawes, Melissa; Peter, Martina; Souza, Romulo; Rixen, Christian; Hagedorn, Frank

2017-04-01

Increased CO2 emissions and global warming may alter the composition of fungal communities through the reduction of low temperature limitation in the plant-soil system, faster nitrogen cycling and changes in the carbon allocation of host plants to the rhizosphere. Shifts in fungal community composition due to global changes are likely to affect the routes of carbon and nitrogen flows in the plant-soil system and alter the rates at which organic matter is decomposed. The main aim of our study was to estimate the effects of multiple years of free air CO2 enrichment (ambient concentration +200 ppm) and soil warming (+ 4°C) on the fungal community structure and composition. At an alpine treeline in Switzerland featuring two key high-elevation tree species, Larix decidua and Pinus uncinata, fungal communities within different organic horizons were analysed by high-throughput 454-pyrosequencing of ITS2 amplicons. In addition, we assessed the ectomycorrhizal community composition on root tips and monitored changes in sporocarp productivity of fungal species during the course of the experiment. Three years of experimental warming at the alpine treeline altered the composition of the fungal community in the organic horizons, whereas nine years of CO2 enrichment had only weak effects. Tree species influenced the composition of the fungal community and the magnitude of the responses of fungal functional groups to soil warming differed between plots with Larix and those with Pinus. The abundance of ectomycorrhizal fungi was positively correlated with nitrogen availability, and ectomycorrhizal taxa specialized for conditions of high nitrogen availability proliferated with warming, corresponding to considerable increases in extractable inorganic nitrogen in warmed soils. Changes in productivity of specific fungal fruiting bodies in response to soil warming (e.g. more Lactarius rufus sporocarps and less Hygrophorus speciousus sporocarps) were consistent with the 454-sequencing data and the colonization of ectomycorrhizal root tips. Several fungal taxa known to be involved in needle degradation responded positively to the warming treatment by increasing in their relative abundance. These findings provide novel insights into the spatial distribution of functional groups of fungi both vertically in the soil and between different rhizospheres of trees. Moreover, they indicate that traits related to nitrogen utilization are important in determining responses of ectomycorrhizal fungi to warming in cold regions, such as high-elevation ecosystems, with low N availability. Shifts in the overall fungal community composition in response to higher temperatures may alter fungal-driven processes with potential feedbacks on ecosystem nitrogen cycling and carbon storage at the alpine treeline.

Experimental soil warming at the treeline shifts fungal communities species

NASA Astrophysics Data System (ADS)

Solly, Emily; Lindahl, Björn; Dawes, Melissa; Peter, Martina; Rixen, Christian; Hagedorn, Frank

2016-04-01

In terrestrial ecosystems, fungi play a major role in decomposition processes, plant nutrient uptake and nutrient cycling. In high elevation ecosystems in Alpine and Arctic regions, the fungal community may be particularly sensitive to climate warming due to the removal of temperature limitation in the plant and soil system, faster nutrient cycling and changes in plant carbon allocation to maintain roots systems and sustain the rhizosphere. In our study, we estimated the effects of 9 years CO2 enrichment and three years of experimental soil warming on the community structure of fungal microorganisms in an alpine treeline ecosystem. In the Swiss Alps, we worked on a total of 40 plots, with c. 40-year-old Larix decidua and Pinus mugo ssp. uncinata trees (20 plots for each tree species). Half of the plots with each tree species were randomly assigned to an elevated CO2 treatment (ambient concentration +200 ppm), whereas the remaining plots received no supplementary CO2. Five individual plots for each combination of CO2 concentration and tree species were heated by an average of 4°C during the growing season with heating cables at the soil surface. At the treeline, the fungal diversity analyzed by high-throughput 454-sequencing of genetic markers, was generally low as compared to low altitude systems and mycorrhizal species made a particularly small contribution to the total fungal DNA. Soil warming led to a shift in the structure and composition of the fungal microbial community, with an increase of litter degraders and ectomycorrhizal fungi. We further observed changes in the productivity of specific fungal fruiting bodies (i.e. more Lactarius rufus sporocarps and less Hygrophorus lucorum sporocarps) during the course of the experiment, that were consistent with the 454-sequencing data. The warming effect was more pronounced in the Larix plots. These shifts were accompanied by an increased soil CO2 efflux (+40%), evidence of increased N availability and a substantial reduction in fine root biomass (-40%) in warmed soils. In comparison, CO2 enrichment had a weaker effect on the composition of the fungal community. Collectively, our results show that soil warming alters fungal communities both directly, by higher temperature, and indirectly, by an improved nitrogen availability associated with an enhanced SOM cycling. These changes may have a vital effect on several ecosystem processes and, in particular, may alter the rate at which soil organic matter is formed and decomposed.

Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua.

PubMed

Bulun, S E; Mahendroo, M S; Simpson, E R

1993-06-01

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for the presence of P450arom transcripts in normal endometrium, decidualized endometrium, or endometrial stromal cells in culture. In our hands, assay of aromatase activity using [3H]water release from [3H]androstenedione by endometrial stromal cells in culture treated with MPA and E2, did not reveal any detectable aromatase activity. The same cells responded to MPA plus E2 treatment by a significant increase in PRL secretion into the culture medium. Presently, RT-PCR is the most sensitive method available for the detection of specific mRNA species in low copy numbers. These findings are indicative of the absence of P450arom transcripts in normal human endometrium.

The denitrification properties of soils under three different shelterbelts and in adjoining cultivated fields

NASA Astrophysics Data System (ADS)

Szajdak, L.; Augustin, J.; Gaca, W.; Meysner, T.; Styla, K.

2009-04-01

The investigations were carried out in Agroecological Landscape Park in Turew (40 km South-West of Poznań). Intensively agricultural is observed in this region. Characteristic features of this landscape are shelterbelts created in the XIX century by general Dezydery Chlapowski. All shelterbelts and adjoining cultivated fields were introduced on Hapludalfs soils. Three shelterbelts and adjoining cultivated fields were selected for this experiment. Two of them were created approximately 200 years ago. The first shelterbelt consists mainly of Robinia pseudoacacia and small admixture Quercus robur and Quercus petraea. The second one consists of Crataegus monogyna. The third one - a young shelterbelt was created in 1993 and consists of several species of plants such as: Quercus petraea and Quercus robur, Larix deciduas, Pinus sylvestris, Sorbus aucuparia, Sorbus intermedia, Tilia cordata and some other tree species. On soils were determinated: activity of nitrate reductase, activity of peroxidase, activity of urease and activity of xantine oxidase, total iron, Fe+3, Fe+2, total nitrogen, N-NH4+, N-NO3-, total organic carbon (TOC), dissolved organic carbon (DOC), current N2O, N2 and CH4 flux rates, and pH (in 1M KCl). The contents of total organic carbon, dissolved organic carbon, total nitrogen, N-NO3- and N-NH4+ were higher in the soil under old shelterbelts (Robinia pseudoacacia and Crataegus monogyna) than under young one. It points out the highest accumulation of organic matter in soils under two old shelterbelts. The same also applied to the current N2O and N2 fluxes. Unlike this CH4exchange was just low everywhere. Nitrate reductase, urease, xantine oxidase and peroxidase activities participates in the cycle of nitrogen and are sensitive on redox potential in soil. The highest activity of nitrate reductase and xantine oxidase activity were observed in young shelterbelt. Activity of urease and activity of peroxidase were higher under two old shelterbelts Robinia pseudoacacia and Crataegus monogyna than in young one and in adjoining cultivated fields. The conversion of Fe+2 into Fe+3 plays an important role in redox processes in soil. Our results have shown that total iron concentrations were higher in soils under three shelterbelts than in adjoining cultivated fields. It was found that pH ranged from 3.29 to 5.98 in soils under shelterbelts and in soils cultivated fields from 4.17 to 6.22. It is one of the factors controlling the rate of denitrification in soil. This work was supported by a grant No. N N305 121934 founded by Polish Ministry of Education.

The enigma of effective pathlength for 18O enrichment in leaf water of conifers

NASA Astrophysics Data System (ADS)

Roden, J. S.; Kahmen, A.; Buchmann, N. C.; Siegwolf, R. T.

2013-12-01

The stable isotopes of oxygen (δ18O) in tree ring cellulose provide valuable proxy information about past environments and climate. Mechanistic models have been used to clarify the important drivers of isotope fractionation and help interpret δ18O variation in tree rings. A critical component to these models is an estimate of leaf water enrichment. However, standard models seldom accurately predict 18O enrichment in conifer needles and Péclet corrections often require effective pathlengths (L) that seem unreasonable from the perspective of needle morphology (>0.5 m). To analyze the potential role of path length on the Péclet effect in conifers we carried out experiments in controlled environment chambers. We exposed seedlings of six species of conifer (Abies alba, Larix decidua, Picea abies, Pinus cembra, P. sylvestris, Taxus bacata), that differ in needle morphology, to four different vapor pressure deficits (VPD), in order to modify transpiration rates (E) and leaf water 18O enrichment. Environmental and δ18O data (leaf, stem and chamber water vapor) were collected to parameterize leaf water models. Cross-sections of needles were sampled for an analysis of needle anatomy. Conifer needles have a single strand of vascular tissue making pathlength determinations through anatomical assessments possible. The six species differed in mesophyll distance (measured from endodermis to epidermis) and cell number, with Pinus and Picea species having the shortest distance and Abies and Taxus the longest (flat needle morphology). Other anatomical measures (transfusion distance, cell size etc.) did not differ significantly. A suberized strip was apparent in the endodermis of all species except Taxus and Abies. Conifer needles have a large proportion (from 0.2 to 0.4) of needle cross-sectional area in vascular tissues that may not be subject to evaporative enrichment. As expected, leaf water δ18O and E responded strongly to VPD and standard models (Craig-Gordon) overestimated leaf water δ18O. A single species-specific value for L could not be determined as the fractional difference between modeled and measured leaf water δ18O did not increase with E as theory predicts. Accounting for potentially unenriched water in vascular and transfusion tissues as well as a Péclet correction that allows the value for L to change with E (as in Song et al., 2013) produced accurate predictions of leaf water δ18O. Estimates of L (for a given E) were positively correlated with mean mesophyll thickness, which to our knowledge is the first time L has been related to a leaf anatomical measure. We repeated the experiment using young needles with much higher values for E, and found a continuing trend of reduced fractional difference with E, implying that Péclet corrections may need to be modified to predict conifer needle water over the range of needle phenology and physiology. Our study will help to better quantify effective pathlength and needle water δ18O in conifers, which are some of the most important organisms used for paleoclimate reconstruction.

Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies.

PubMed

Moser, Gerit; Drewlo, Sascha; Huppertz, Berthold; Armant, D Randall

2018-03-28

Early during human development, the trophoblast lineage differentiates to commence placentation. Where the placenta contacts the uterine decidua, extravillous trophoblast (EVT) cells differentiate and invade maternal tissues. EVT cells, identified by expression of HLA-G, invade into uterine blood vessels (endovascular EVT), as well as glands (endoglandular EVT), and open such luminal structures towards the intervillous space of the placenta. Endoglandular invasion diverts the contents of uterine glands to the intervillous space, while glands near the margin of the placenta that also contain endoglandular EVT cells open into the reproductive tract. Cells of the trophoblast lineage have thus been recovered from the uterine cavity and endocervical canal. An emerging non-invasive technology [trophoblast retrieval and isolation from the cervix (TRIC)] isolates and examines EVT cells residing in the cervix to explore their origin, biology and relationship to pregnancy and fetal status. This review explores the origins and possible uses of trophoblast cells obtained during ongoing pregnancies (weeks 5-20) by TRIC. We hypothesize that endoglandular EVT cells at the margins of the expanding placenta enter the uterine cavity and are carried together with uterine secretion products to the cervix where they can be retrieved from a Papanicolaou (Pap) smear. The advantages of TRIC for investigation of human placentation and prenatal testing will be considered. Evidence from the literature, and from archived in utero placental histological sections, is presented to support these hypotheses. We used 52 out of 80 publications that appeared between 1966 and 2017 and were found by searching the PubMed and Google Scholar databases. The studies described trophoblast invasion of uterine vessels and glands, as well as trophoblast cells residing in the reproductive tract. This was supplemented with literature on human placental health and disease. The literature describes a variety of invasive routes taken by EVT cells at the fetal-maternal interface that could displace them into the reproductive tract. Since the 1970s, investigators have attempted to recover trophoblast cells from the uterus or cervix for prenatal diagnostics. Trophoblast cells from Pap smears obtained at 5-20 weeks of gestation have been purified (>95% β-hCG positive) by immunomagnetic isolation with nanoparticles linked to anti-HLA-G (TRIC). The isolated cells contain the fetal genome, and have an EVT-like expression profile. Similar EVT-like cells appear in the lumen of uterine glands and can be observed entering the uterine cavity along the margins of the placenta, suggesting that they are the primary source of cervical trophoblast cells. Cells isolated by TRIC can be used to accurately genotype the embryo/fetus by targeted next-generation sequencing. Biomarker protein expression quantified in cervical trophoblast cells after TRIC correlates with subsequent pregnancy loss, pre-eclampsia and fetal growth restriction. A key remaining question is the degree to which EVT cells in the cervix might differ from those in the basal plate and placental bed. TRIC could one day provide a method of risk assessment for maternal and fetal disease, and reveal molecular pathways disrupted during the first trimester in EVT cells associated with placental maldevelopment. As perinatal interventions emerge for pregnancy disorders and inherited congenital disorders, TRIC could provide a key diagnostic tool for personalized precision medicine in obstetrics.

Investigations with large-scale forest lysimeter research of the lowlands of Northeast Germany - Results and consequences for the choice of tree species and forest management

NASA Astrophysics Data System (ADS)

Müller, J.

2009-04-01

Investigations with large-scale forest lysimeter research of the lowlands of Northeast Germany - Results and consequences for the choice of tree species and forest management Introduction At present about 28 % - i.e. 1.9 million hectares - of the Northeast German Lowlands are covered with forests. The Lowlands are among the driest and at the same time the most densely wooded regions in Germany. The low annual precipitation between 500 and 600 mm and the light sandy soils with their low water storage capacity and a high porosity lead to a limited water availability. Therefore the hydrological functions of forests play an important role in the fields of regional water budget, water supply and water distribution. Experimental sites Lysimeters are suitable measuring instruments in the fields of granular soils and loose rocks to investgate evaporation and seepage water. The usage of lysimeter of different construction has a tradition of more than 100 years in this region. To investigate the water consumption of different tree species, lysimeters were installed at Britz near Eberswalde under comparable site conditions. In the early 1970s nine large-scale lysimeters were built with an area of 100 m2 and a depth of 5 m each. In 1974 the lysimeters were planted, together with their environment, with Scots pine (Pinus sylvestris L), common beech (Fagus sylvatica L.), larch (Larix decidua L.) and Douglas-fir (Pseudotsuga menziesii [Mirb.] FRANCO) as experimental stands of 0.5 ha each according to the usual management practices. Therefore the "Large-scale lysimeters of Britz" are unparalleled in Europe. It was the initial aim of the experiment to find out the influence of the species and age of the growing stock growing on identical sandy soil under comparable weather conditions on both natural groundwater recharge and evaporation. Future forests in the north-eastern lowlands of Germany shall be mixed stands with as large a number of different species as possible. And this is also the aim of forest conversion in Land Brandenburg. The programme requires scientific attendance and foundation. In particular it shall be examined how the hydro-ecological conditions - which often are the limiting factor for forest growth in this area - would change with underplanted pine and larch and how these conditions may benefit from stand-structural and forestry measures. This is why several lysimeter stands were changed as follows: Ø Larch underplanted with beech Ø Scots pine underplanted with beech Ø Scots pine underplanted with oak Results Forests with their special hydrological properties have a substantial influence on the water budget, water supply and water distribution of entire landscapes. The tree species is of outstanding importance for deep seepage under forest stands. The sum of transpiration gives a rough overview about the water budget of the forest stand. More important for the detection of interactions between the compartments is the partitioning of the whole evaporation into individual evaporation components. Under the given precipitation and soil conditions, the course of interception and hence, the amount of seepage water depend on the crown structure in the stand. Depending on the amount of interception of the tree canopy and the duration of the leaching phase in spring, the mixed stands range between pure pine and pure beech. Making use of silvicultural methods and adequate stand treatment, forestry is able to control the water budget of landscapes.

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

PubMed

Vasilopoulou, E; Loubière, L S; Lash, G E; Ohizua, O; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S Y

2014-06-01

Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated. Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1β (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-α secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory 'switch' in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes. This study is funded by Wellbeing of Women (RG/1082/09 to S.Y.C., M.D.K., J.A.F., L.S.L., G.E.L.) and Action Medical Research - Henry Smith Charity (SP4335 to M.D.K., S.Y.C., L.S.L., J.A.F.). The authors have no conflicts of interest to disclose.

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner

PubMed Central

Vasilopoulou, E.; Loubière, L.S.; Lash, G.E.; Ohizua, O.; McCabe, C.J.; Franklyn, J.A.; Kilby, M.D.; Chan, S.Y.

2014-01-01

STUDY QUESTION Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION This laboratory-based study used human decidua from first (8–11 weeks; n = 18) and second (12–16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10−) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel® was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1β (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-α secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. LIMITATIONS, REASONS FOR CAUTION Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. WIDER IMPLICATIONS OF THE FINDINGS Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory ‘switch’ in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study is funded by Wellbeing of Women (RG/1082/09 to S.Y.C., M.D.K., J.A.F., L.S.L., G.E.L.) and Action Medical Research – Henry Smith Charity (SP4335 to M.D.K., S.Y.C., L.S.L., J.A.F.). The authors have no conflicts of interest to disclose. PMID:24626803