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Sample records for placental extracts

  1. Preventive and therapeutic potential of placental extract in contact hypersensitivity

    PubMed Central

    Kim, Youn Son; Park, Jang-June; Sakoda, Yukimi; Zhao, Yuming; Hisamichi, Katsuya; Kaku, Tai-ichi; Tamada, Koji

    2010-01-01

    Immunoregulatory effects of placental extract and placenta-derived factors have been demonstrated in various conditions. Accordingly, placental extract has been used as certain types of medical intervention in Asian countries, whereas experimental evidence supporting its therapeutic effects and mechanisms has yet to be fully demonstrated. In this study, we investigate preventive and therapeutic effects of placental extract in contact hypersensitivity (CHS), a mouse model of allergic contact dermatitis. Administration of placental extract prior to the sensitization of allergic antigen (Ag) significantly inhibited the severity of CHS induced by Ag challenge. This effect was associated with reduced numbers of CD4+ T cells in peripheral blood, decrease of tissue-infiltrating lymphocytes, and preferential production of Th2-type cytokines in Ag-challenged sites. In addition, CHS caused by repetitive challenges of allergic Ag was also prevented and treated by administration of placental extract. Finally, administration of cyclo-trans-4-Lhydroxyprolyl-L-serine, a dipeptide derived from placental extract, also alleviated CHS, suggesting its potential role in the effects of placental extract in CHS. Taken together, our findings demonstrated experimental evidence supporting immunoregulatory effects of placental extract in allergic skin diseases and elucidated its potential mechanisms. PMID:20619383

  2. Therapeutic effect of acupuncture point injection with placental extract in knee osteoarthritis.

    PubMed

    Park, Kyeong Mee; Cho, Tae Hwan

    2017-03-01

    This study evaluated the effectiveness of acupuncture point injection (API) with placental extract on pain reduction and joint function in patients with knee osteoarthritis (OA). Fifty-two patients with knee OA, with an average age of 64, and having a symptom duration of more than 3 months were studied in this report. Placental extract was injected weekly into acupuncture point ST35, BL23, BL24 and BL25 for 5 weeks; 8 mL of placental extract into ST35 on the affected side, and 1 mL of placental extract to BL23, BL24 and BL25 bilaterally. After a five-week treatment of API with placental extract, pain was substantially decreased in patients of all Kellgren-Lawrence (KL) grades. Improvement of knee joint swelling was also apparent. Decrease of pain and joint swelling improved daily working productive time among patients of all KL grades. Study results imply that API with placental extract is a potentially useful therapy to control pain and maintain joint functions in knee OA patients.

  3. An effective placental cotyledons proteins extraction method for 2D gel electrophoresis.

    PubMed

    Tan, Niu J; Daim, Leona D J; Jamil, Amilia A M; Mohtarrudin, Norhafizah; Thilakavathy, Karuppiah

    2017-03-01

    Effective protein extraction is essential especially in producing a well-resolved proteome on 2D gels. A well-resolved placental cotyledon proteome, with good reproducibility, have allowed researchers to study the proteins underlying the physiology and pathophysiology of pregnancy. The aim of this study is to determine the best protein extraction protocol for the extraction of protein from placental cotyledons tissues for a two-dimensional gel electrophoresis (2D-GE). Based on widely used protein extraction strategies, 12 different extraction methodologies were carefully selected, which included one chemical extraction, two mechanical extraction coupled protein precipitations, and nine chemical extraction coupled protein precipitations. Extracted proteins were resolved in a one-dimensional gel electrophoresis and 2D-GE; then, it was compared with set criteria: extraction efficacy, protein resolution, reproducibility, and recovery efficiency. Our results revealed that a better profile was obtained by chemical extraction in comparison to mechanical extraction. We further compared chemical extraction coupled protein precipitation methodologies, where the DNase/lithium chloride-dense sucrose homogenization coupled dichloromethane-methanol precipitation (DNase/LiCl-DSH-D/MPE) method showed good protein extraction efficiency. This, however, was carried out with the best protein resolution and proteome reproducibility on 2D-gels. DNase/LiCl-DSH-D/MPE was efficient in the extraction of proteins from placental cotyledons tissues. In addition, this methodology could hypothetically allow the protein extraction of any tissue that contains highly abundant lipid and glycogen.

  4. Infectious Achilles Tendinitis After Local Injection of Human Placental Extracts: A Case Report.

    PubMed

    Kim, Yoon-Chung; Ahn, Jae Hoon; Kim, Man-Soo

    2015-01-01

    Local injections of corticosteroids or human placental extracts are sometimes used for the treatment of resistant tendinitis or fasciitis. We report a case of infectious Achilles tendinitis complicated by calcaneal osteomyelitis after injection of human placental extracts for the Achilles tendinitis. She was treated with excision of the infected bone and tendon, followed by V-Y lengthening of the proximal portion of the Achilles tendon in a single stage. At 2 years postoperative, she remained symptom free without any signs of recurrence, and the follow-up magnetic resonance imaging scan demonstrated a well-maintained Achilles tendon with normal signal intensity. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Autologous bone marrow-derived cells with placental extract for healing excisional cutaneous wounds in animal model.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Das, Partha; Banerjee, Dibyajyoti; Roy, Subhasis; Datta, Uttam

    2013-04-01

    Topical wound-healing potential of autologous bone marrow-derived nucleated cells along with placental extract was evaluated in comparison with buffy coat of autologous blood on full-thickness cutaneous wounds in the thoracolumbar region of 15 clinically healthy New Zealand rabbits. Three wounds of 2 × 2 cm, one on the right side of the body and two on the left side of the midline were created on the dorsal lumbar region of each rabbit under xylazine-ketamine anaesthesia. The wounds of each animal were randomly assigned to one of the three treatments: topical application of autologous bone marrow-derived cells with placental extract (group I), application of buffy coat in the autologous plasma with placental extract (group II) and autologous plasma with placental extract as control (group III). Wounds were observed for 30 days macroscopically and for granulation tissue formation, histomorphological and histochemical evaluation. Time of appearance of granulation tissues and filling of wound beds were faster in group I followed by group II and group III animals, respectively. Histomorphological findings exhibited an earlier disappearance of inflammatory reaction, better epithelialisation, significantly maximum neovascularisation, fibroplasias and collagenation in group I followed by group II and group III animals, respectively. Histochemical findings also depicted maximum number of robust, thick, interwoven type of collagen fibres, stout, highly tortuous and interwoven network of elastin fibres and numerous mesh war form of reticulin fibres within the dermal component were present in group I when compared with group II and III animals. Experiment conclude that single application of autologous bone marrow-nucleated cells with placental extract topically could be a novel option for faster healing in complicated non healing wounds both in human beings and animals. © 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines

  6. Membrane-active antimicrobial peptides and human placental lysosomal extracts are highly active against mycobacteria.

    PubMed

    Jena, Prajna; Mishra, Bibhuti; Leippe, Matthias; Hasilik, Andrej; Griffiths, Gareth; Sonawane, Avinash

    2011-05-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, manifests discreet strategies to subvert host immune responses, which enable the pathogen to survive and multiply inside the macrophages. This problem is further worsened by the emergence of multidrug resistant mycobacterial strains, which make most of the anti-tuberculous drugs ineffective. It is thus imperative to search for and design better therapeutic strategies, including employment of new antibiotics. Recently, naturally produced antimicrobial molecules such as enzymes, peptides and their synthetic analogs have emerged as compounds with potentially significant therapeutical applications. Although, many antimicrobial peptides have been identified only very few of them have been tested against mycobacteria. A major limitation in using peptides as therapeutics is their sensitivity to enzymatic degradation or inactivity under certain physiological conditions such as relatively high salt concentration. Here, we show that NK-2, a peptide representing the cationic core region of the lymphocytic effector protein NK-lysin, and Ci-MAM-A24, a synthetic salt-tolerant peptide derived from immune cells of Ciona intestinalis, efficiently kill Mycobacterium smegmatis and Mycobacterium bovis-BCG. In addition, NK-2 and Ci-MAM-A24 showed a synergistic killing effect against M. smegmatis, no cytotoxic effect on mouse macrophages at bactericidal concentrations, and were even found to kill mycobacteria residing inside the macrophages. We also show that human placental lysosomal contents exert potent killing effect against mycobacteria under acidic and reducing growth conditions. Electron microscopic studies demonstrate that the lysosomal extract disintegrate bacterial cell membrane resulting in killing of mycobacteria.

  7. Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth Opening and Wound Healing in Patients With Oral Submucous Fibrosis?

    PubMed

    Thakur, Gagan; Thomas, Shaji; Bhargava, Darpan; Pandey, Ankit

    2015-07-01

    Placental extract has been used as a therapeutic agent with application in various fields of medicine. Placental extract is well known for its effects on wound healing with anti-inflammatory, antiplatelet, and angiogenic effects and is also a biogenic modulator. The present study evaluated the effect of placental extract on wound healing, mouth opening, and postoperative patient discomfort in patients with oral submucous fibrosis treated with fibrotomy with buccal fat pad coverage and coronoidectomy. Ten subjects with oral submucous fibrosis who presented with mouth opening less than 20 mm were enrolled in the present prospective randomized controlled trial to assess the effects of placental extract on the fibrotomy wound covered with a pedicled buccal pad fat (5 patients allocated to the study group, group S and 5 to the control group, group C). The following criteria were used to analyze the postoperative effect of placental extract on fibrotomy wounds compared with that of the controls: subjective assessment of the wound, postoperative discomfort, and postoperative mouth opening assessed at 1, 2, and 4 weeks postoperatively. The average difference in the preoperative and fourth week postoperative mouth opening for group C was 13.8 ± 2.68 mm and was 21.20 ± 2.77 mm in group S. The median calculated for group C was a 15.0-mm increase in mouth opening and was 20.0 mm in group S. The results obtained with topical application of placental extract on fibrotomy wound healing and postoperative mouth opening were superior to those of the control group in whom placental extract was not used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  8. [Effect of the protein-free calf-blood-extract (Solcoseryl) on the excretion of estrogens in chronic placental insufficiency].

    PubMed

    Herre, H D; Kyank, H; Adomssent, S; Wilken, H P

    1976-01-01

    In a double blind study the action of Solcoseryl was tested in 31 patients during late pregnancy with chronic placental insufficiency. Under treatment with Solcoseryl a significant increase in urinary estrogen excretion occurred in relation to the placebo-group.

  9. Placental hypoxia during placental malaria

    PubMed Central

    Boeuf, Philippe; Tan, Aimee; Romagosa, Cleofe; Radford, Jane; Mwapasa, Victor; Molyneux, Malcolm E.; Meshnick, Steven R.; Hunt, Nicholas H.; Rogerson, Stephen J.

    2009-01-01

    Background Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR. Methods We studied the hypoxia markers hypoxia inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), placental growth factor, VEGF receptor 1 and its soluble form and VEGF receptor 2. We used real time PCR (in 59 women) to examine gene transcription, immunohistochemistry (in 30 women) to describe protein expression and laser capture microdissection (in 23 women) to examine syncytiotrophoblast-specific changes in gene expression. We compared gene and protein expression in relation to malaria infection, monocytes infiltrates and birth weight. Results we could not associate any hallmark of placental malaria with a transcription, expression or tissue distribution profile characteristic of a response to hypoxia but found higher HIF-1α (P=.0005) and lower VEGF levels (P=.0026) in the syncytiotrophoblast of malaria cases versus asymptomatic controls. Conclusion our data are inconsistent with a role for placental hypoxia in the pathogenesis of malaria-associated FGR. The laser capture microdissection study was small, but suggests that malaria affects syncytiotrophoblast gene transcription, and proposes novel potential mechanisms for placental malaria-associated FGR. PMID:18279052

  10. Placental insufficiency

    MedlinePlus

    ... due date High blood pressure during pregnancy (called preeclampsia ) Medical conditions that increase the mother's chances of ... have any symptoms. However, certain diseases, such as preeclampsia, which can be symptomatic, can cause placental insufficiency.

  11. Human Placental Extract Ameliorates Structural Lung Changes Iinduced by Amiodarone in Rats.

    PubMed

    Samiei, Fatemeh; Jamshidzadeh, Akram; Noorafshan, Ali; Ghaderi, Amir

    2016-01-01

    Amiodarone is used in treatment of cardiac arrhythmias. Therapeutic use of amiodarone is limited by its side effects, including pulmonary toxicity. Human Placenta Extract (HPE) contains a variety of bio-active substances. Thus, the present study aimed to quantitatively evaluate the protective effects of HPE on the structural lung changes induced by amiodarone using stereological methods. Sprague-Dawley male rats were divided into four groups. The first, second, and third groups received no treatment, amiodarone (100 mg/kg, i.p.), and HPE (500 µL/kg, i.p.), respectively. The fourth group was treated with amiodarone + HPE. The animals' lungs were removed after 10 days. The lung volume was estimated using the Cavalieri principle on the embedded and cut tissue and corrected for shrinkage. The volume density of the parenchyma, alveolar space, and septa were estimated using point-counting method. The surface area of the alveoli, the volume-weighted means alveoli volume, and mean septum thickness were also estimated in all groups. The total volume and thickness of the alveolar septum were increased by 40 % and 28 %, respectively. However, the total volume of the alveolar space was decreased by 31 % in the amiodarone treated-rats. The mean alveolar volume was decreased by 64 % on the average in the amiodarone treated group. Yet, these changes were not detected in the amiodarone+HPE group. Moreover, RBC accumulation in the alveolar space and septa was ameliorated after HPE treatment. HPE can protect the lung tissue from the structural changes induced by amiodarone.

  12. High-protein-low-carbohydrate diet during pregnancy alters maternal plasma amino acid concentration and placental amino acid extraction but not fetal plasma amino acids in pigs.

    PubMed

    Metzler-Zebeli, Barbara U; Lang, Iris S; Görs, Solvig; Brüssow, Klaus-Peter; Hennig, Ulf; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried; Metges, Cornelia C

    2012-12-28

    A high protein-low-carbohydrate diet during pregnancy can cause intra-uterine growth restriction. However, its impact during pregnancy on maternal, umbilical and fetal plasma amino acid (AA) profiles is unknown. A maternal high-protein (30 %)-low-carbohydrate (HP-LC) diet was compared with isoenergetic standard (12·1 % crude protein; ST) and low-protein (6·5 %)-high-carbohydrate (LP-HC) diets fed to nulliparous pregnant sows to examine changes in AA concentrations in maternal, venous and arterial umbilical and fetal plasma in mid and late pregnancy. At 64 and 94 days of pregnancy (dp), sows underwent Caesarean section, and maternal, umbilical and fetal plasma samples were collected. The HP-LC diet mainly affected maternal plasma AA concentrations. Plasma concentrations of Ile and Val were increased and those of Ala, Glu and Gly were decreased (P ≤ 0·05) in HP-LC compared with ST sows at 64 and 94 dp. The LP-HC diet decreased fetal plasma Glu concentration compared with the ST diet at 94 dp. Substantial AA catabolism was reflected by increased (P ≤ 0·05) maternal and fetal plasma urea concentrations with the HP-LC compared with the ST and LP-HC diets at 94 dp. Fractional placental extraction of Val was higher whereas those of Ala, Gln and Glu were lower in the HP-LC compared with the ST sows at 64 and 94 dp (P ≤ 0·05). Reduced fetal mass at 94 dp was accompanied by reduced fetal extraction of Lys and Pro in the HP-LC group (P ≤ 0·05). In conclusion, a maternal HP-LC diet during pregnancy altered maternal plasma composition of many AA and modified placental AA extraction to compensate for imbalanced maternal nutrient intake.

  13. Fusarium moniliforme extract fed before a single dose of diethylnitrosamine increases the numbers of placental glutathione S-transferase positive hepatocytes in rat liver

    SciTech Connect

    Lebepe, S.; Hendrich, S. )

    1991-03-11

    The carcinogenic potential of an alcohol:water (1:1) extract of Fusarium moniliforme (FUSX), containing 20 ppm fumonisin B{sub 1} was assayed. Groups of six 5-week-old female F344/N rats were fed a semipurified diet, with and without FUSX. A dose of initiating agent, diethylnitrosamine, was given orally. Placental glutathione S-transferase-positive (PGST(+)) hepatocytes were detected by immunohistochemistry and counted on 5 frozen hepatic sections/rat, as an endpoint to assess early stages of carcinogenesis. FUSX had significant co-initiating activity. Fusarium moniliforme infection of feed has been shown to promote hepatocarcinogenesis, and may pose a cocarcinogenic risk even during short-term, low-level exposure.

  14. Comparison of Therapeutic Efficacy of Placental Extract with Dexamethasone and Hyaluronic Acid with Dexamethasone for Oral Submucous Fibrosis - A Retrospective Analysis

    PubMed Central

    Venkatesh, Rashmi; More, Chandramani Bhagawan; Vassandacoumara, Vaishnavee

    2016-01-01

    Introduction Oral Submucous Fibrosis (OSMF) is a potentially malignant disease of the oral cavity associated with betel nut chewing. The management of OSMF has been a subject of controversy and no definitive and widely accepted treatment is currently available for this condition. Aim To retrospectively evaluate the therapeutic efficacy of two treatment regimens (placental extract with dexamethasone and hyaluronic acid with dexamethasone) for the treatment of OSMF. Materials and Methods The records of the patients diagnosed with OSMF were obtained from the departmental archives. A total of 25 records were selected and divided into two study groups based on the treatment regimens, as Group A (placental extract + dexamethasone) and Group B (hyaluronidase + dexamethasone). The records were studied for improvement in mouth opening and reduction in burning sensation. Descriptive statistics, paired t test and student’s t test were used for statistical analysis. Results In Group A and Group B, the average increase in mouth opening from baseline record to 8th week of treatment was 3.53±1.26mm and 3.65±1.42mm respectively and average decrease in burning sensation, noted by VAS scale, was 5.13±1.13 and 4.90 ±1.29 respectively. The pre- and post-treatment differences were found to be statistically significant for both the groups (p<0.001) and for both the treatment outcomes. When the average difference of the treatment outcomes was compared between the two study groups, no statistically significant difference was noted (p>0.05). Conclusion The results of the present study indicate that both the treatment regimens studied are equally effective in the treatment of oral submucous fibrosis. PMID:27891461

  15. Human placental extract exerts hair growth-promoting effects through the GSK-3β signaling pathway in human dermal papilla cells.

    PubMed

    Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Park, Hye Min; Han, Hae Jung; Ji, Hyi Jeong; Kim, Beom Joon

    2015-10-01

    Human placental extract (HPE) is widely used in Korea to relieve fatigue. However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the present study, in an effort to develop novel therapies to promote hair growth, we screened HPE. We demonstrate that HPE has hair growth‑promoting activities and induces β‑catenin expression through the inhibition of glycogen synthase kinase‑3β (GSK‑3β) by phosphorylation in hDPCs. Treatment with HPE significantly increased the viability of the hDPCs in a concentration‑dependent manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly increased the alkaline phosphatase (ALP) expression levels. The increased β‑catenin levels and the inhibition of GSK‑3β (Ser9) by phosphorylation suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the effects of treatment with HPE alone and treatment with HPE in conjunction with minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK‑3β by phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was effective in inducing root hair elongation in rat vibrissa hair follicles, and that treatment with HPE led to a delay in catagen progression. Overall, our findings suggest that HPE promotes hair growth and may thus provide the basis of a novel therapeutic strategy for the clinical treatment of hair loss.

  16. Molecular weight forms of inhibin A, inhibin B and pro-alphaC in maternal serum, amniotic fluid and placental extracts of normal and Down syndrome pregnancies.

    PubMed

    Thirunavukarasu, P P; Lambert-Messerlian, G; Robertson, D M; Dawson, G; Canick, J; Wallace, E M

    2002-12-01

    Inhibin A, an established prenatal marker of Down syndrome (DS), exists in the maternal circulation in a number of isoforms. The present study explored whether specific inhibin A isoforms may be selectively increased in DS, offering the prospect of improved marker performance. Second trimester maternal serum, placental extracts and amniotic fluid (AF) pools from both normal and DS pregnancies were fractionated by a combined immunoaffinity (IA) chromatography, preparative polyacrylamide gel electrophoresis (Prep-PAGE) and electroelution procedure. Inhibins A, B and pro-alphaC were determined in the eluted fractions by specific enzyme-linked immunosorbent assays (ELISAs) and the profiles of immunoactivity (IA) characterized in terms of molecular weight (MW) and percentage recovery. The MW patterns of inhibin A and pro-alphaC in maternal serum and AF were similar between DS and control pregnancies, both showing peaks between 25-40 k and approximately 65 k. AF contained, in addition, a higher proportion of <30 k inhibins A and B, and <25 k pro-alphaC forms. There were large differences in the inhibin forms present in DS placentae, with more 70 k and less 30-40 k inhibin A than in controls. The present data suggest that the processing, cleavage or secretion of inhibin MW forms by the DS placenta differs from normal. However, these differences are not reflected in maternal serum and so improvements in serum screening will not be afforded by measuring specific inhibin A isoforms. Copyright 2002 John Wiley & Sons, Ltd.

  17. [Immunochemical determination of placenta-specific and interorganic antigens in placental extract and blood serum in pregnant rats].

    PubMed

    Kan, M F; Krivonosov, S K; Tatarinova, Iu S

    1985-04-01

    It has been demonstrated that placenta extract of rats contains up to 14 antigens. Moreover, 11 of them are interorgan proteins of wide and limited specificity, two antigens (alpha 1- and alpha 2-globulins) are attributed to acute-phase proteins typical for pregnancy. beta 1-Globulin is a specific protein of rat placenta. The content of these antigens in blood serum increases with pregnancy and reaches a maximum toward the delivery; 3-4 days after delivery beta 1-globulin disappears completely from maternal blood, whereas the concentration of acute-phase proteins drops to the initial level.

  18. Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly

    PubMed Central

    LIU, GUOHUI; CHEN, XI; ZHOU, WU; YANG, SHUHUA; YE, SHUNAN; CAO, FAQI; LIU, YI; XIONG, YUAN

    2016-01-01

    Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE. PMID:27073463

  19. Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly.

    PubMed

    Liu, Guohui; Chen, X I; Zhou, W U; Yang, Shuhua; Ye, Shunan; Cao, Faqi; Liu, Y I; Xiong, Yuan

    2016-04-01

    Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE.

  20. Cigarette smoke extract induces placental growth factor release from human bronchial epithelial cells via ROS/MAPK (ERK-1/2)/Egr-1 axis

    PubMed Central

    Wu, Dong; Yuan, Yalian; Lin, Zhixiu; Lai, Tianwen; Chen, Min; Li, Wen; Lv, Quanchao; Yuan, Binfan; Li, Dongmin; Wu, Bin

    2016-01-01

    Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF) has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE)-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS)-dependent activation of the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase1/2 [ERK-1/2])/early growth response-1 (Egr-1) pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE). The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2) cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2)/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking-related airway inflammatory diseases. PMID:27980400

  1. Placental transfusion: a review

    PubMed Central

    Katheria, A C; Lakshminrusimha, S; Rabe, H; McAdams, R; Mercer, J S

    2017-01-01

    Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:27654493

  2. Validated method for the determination of perfluorinated compounds in placental tissue samples based on a simple extraction procedure followed by ultra-high performance liquid chromatography-tandem mass spectrometry analysis.

    PubMed

    Martín, J; Rodríguez-Gómez, R; Zafra-Gómez, A; Alonso, E; Vílchez, J L; Navalón, A

    2016-04-01

    Xenobiotic exposure during pregnancy is inevitable. Determination of perfluorinated compounds (PFCs), chemicals described as environmental contaminants by Public Health Authorities due to their persistence, bioaccumulation and toxicity, is a challenge. In the present work, a method based on a simplified sample treatment involving freeze-drying, solvent extraction and dispersive clean-up of the extracts using C18 sorbents followed by an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was developed and validated for the determination of five perfluorinated carboxylic acids (C4-C8) and perfluorooctane sulfonate (PFOS) in placental tissue samples. The most influential parameters affecting the extraction method and clean-up were optimized using Design of Experiments (DOE). The method was validated using matrix-matched calibration. Found limits of detection (LODs) ranged from 0.03 to 2 ng g(-1) and limits of quantification (LOQs) from 0.08 to 6 ng g(-1), while inter- and intra-day variability was under 14% in all cases. Recovery rates for spiked samples ranged from 94% to 113%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at delivery from 25 randomly selected women. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Placental retention in a bonobo (Pan paniscus).

    PubMed

    Halbwax, Michel; Mahamba, Crispin Kamate; Ngalula, Anne-Marie; André, Claudine

    2009-06-01

    This case report describes the first placental retention in an 11-year-old female bonobo (Pan paniscus) following the delivery of a healthy infant. After unsuccessful medical treatment with oxytocin, the placenta was manually extracted. Both the dam and infant survived.

  4. Mosaic retroposon insertion patterns in placental mammals

    PubMed Central

    Churakov, Gennady; Kriegs, Jan Ole; Baertsch, Robert; Zemann, Anja; Brosius, Jürgen; Schmitz, Jürgen

    2009-01-01

    One and a half centuries after Charles Darwin and Alfred Russel Wallace outlined our current understanding of evolution, a new scientific era is dawning that enables direct observations of genetic variation. However, pure sequence-based molecular attempts to resolve the basal origin of placental mammals have so far resulted only in apparently conflicting hypotheses. By contrast, in the mammalian genomes where they were highly active, the insertion of retroelements and their comparative insertion patterns constitute a neutral, virtually homoplasy-free archive of evolutionary histories. The “presence” of a retroelement at an orthologous genomic position in two species indicates their common ancestry in contrast to its “absence” in more distant species. To resolve the placental origin controversy we extracted ∼2 million potentially phylogenetically informative, retroposon-containing loci from representatives of the major placental mammalian lineages and found highly significant evidence challenging all current single hypotheses of their basal origin. The Exafroplacentalia hypothesis (Afrotheria as the sister group to all remaining placentals) is significantly supported by five retroposon insertions, the Epitheria hypothesis (Xenarthra as the sister group to all remaining placentals) by nine insertion patterns, and the Atlantogenata hypothesis (a monophyletic clade comprising Xenarthra and Afrotheria as the sister group to Boreotheria comprising all remaining placentals) by eight insertion patterns. These findings provide significant support for a “soft” polytomy of the major mammalian clades. Ancestral successive hybridization events and/or incomplete lineage sorting associated with short speciation intervals are viable explanations for the mosaic retroposon insertion patterns of recent placental mammals and for the futile search for a clear root dichotomy. PMID:19261842

  5. Mosaic retroposon insertion patterns in placental mammals.

    PubMed

    Churakov, Gennady; Kriegs, Jan Ole; Baertsch, Robert; Zemann, Anja; Brosius, Jürgen; Schmitz, Jürgen

    2009-05-01

    One and a half centuries after Charles Darwin and Alfred Russel Wallace outlined our current understanding of evolution, a new scientific era is dawning that enables direct observations of genetic variation. However, pure sequence-based molecular attempts to resolve the basal origin of placental mammals have so far resulted only in apparently conflicting hypotheses. By contrast, in the mammalian genomes where they were highly active, the insertion of retroelements and their comparative insertion patterns constitute a neutral, virtually homoplasy-free archive of evolutionary histories. The "presence" of a retroelement at an orthologous genomic position in two species indicates their common ancestry in contrast to its "absence" in more distant species. To resolve the placental origin controversy we extracted approximately 2 million potentially phylogenetically informative, retroposon-containing loci from representatives of the major placental mammalian lineages and found highly significant evidence challenging all current single hypotheses of their basal origin. The Exafroplacentalia hypothesis (Afrotheria as the sister group to all remaining placentals) is significantly supported by five retroposon insertions, the Epitheria hypothesis (Xenarthra as the sister group to all remaining placentals) by nine insertion patterns, and the Atlantogenata hypothesis (a monophyletic clade comprising Xenarthra and Afrotheria as the sister group to Boreotheria comprising all remaining placentals) by eight insertion patterns. These findings provide significant support for a "soft" polytomy of the major mammalian clades. Ancestral successive hybridization events and/or incomplete lineage sorting associated with short speciation intervals are viable explanations for the mosaic retroposon insertion patterns of recent placental mammals and for the futile search for a clear root dichotomy.

  6. Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

    PubMed

    Shaban, N Z; Hegazy, W A; Abdel-Rahman, S M; Awed, O M; Khalil, S A

    2016-08-29

    Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

  7. Placental Permeability of Lead

    PubMed Central

    Carpenter, Stanley J.

    1974-01-01

    The detection of lead in fetal tissues by chemical analysis has long been accepted as prima facie evidence for the permeability of the placenta to this nonessential trace metal. However, only a few investigations, all on lower mammalian species, have contributed any direct experimental data bearing on this physiological process. Recent radioactive tracer and radioautographic studies on rodents have shown that lead crosses the placental membranes rapidly and in significant amounts even at relatively low maternal blood levels. While it is not possible to extrapolate directly the results of these experiments to humans because of differences in placental structure and other factors, the results do serve as a warning of the possible hazard to the human embryo and fetus of even low levels of lead in the maternal system. PMID:4857497

  8. Placental apoptosis in recurrent miscarriage.

    PubMed

    Atia, Tarek A

    2017-09-01

    Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM). Placental tissue samples were collected from 40 women with RM (study group) and 30 women with sporadic spontaneous abortion (control group). Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53) and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53) protein was significantly increased in the placental tissues of the RM group (p = 0.003). By contrast, the expression of anti-apoptotic (Bcl-2) antibodies was significantly increased in the placental tissues of the control group (p = 0.025). We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation. Copyright © 2017. Published by Elsevier Taiwan.

  9. Seasonal variation in placental abruption.

    PubMed

    Mankita, Ronen; Friger, Michael; Pariente, Gali; Sheiner, Eyal

    2012-11-01

    To characterize seasonal patterns of placental abruption among Jewish and Bedouin parturients in the Southern part of Israel. A retrospective population-based study comparing all singleton pregnancies of patients with and without placental abruption was conducted. Deliveries occurred between the years 1988 and 2010. A 'classical' model of time series was used, allowing to assess trend and periodic patterns of placental abruption. During the study period, 241,408 deliveries took place, of which 1685 (0.7%) were complicated with placental abruption. Placental abruption was significantly more common among Bedouin parturients: 0.77% (n = 948) vs. 0.623% (n = 737), p < 0.001. A non-linear negative correlation was noted in the incidence of placental abruption (coefficient = -0.002) during the entire study period. Time series analysis demonstrated annual cycle frequency, seasonal cycle and weekly cycle of placental abruption. The seasonal incidence of placental abruption was higher during spring (B = 7.15) and lower during summer (reference) for both populations (Jewish and Bedouins). Weekly cycle showed significantly higher incidence on Saturday (B = 3.4) and lowest on Tuesday (B = -4.66) for both groups. The daily differences were accentuated in the Bedouin population (B = 3.7 vs. B = 2.93 in the Jewish population). Placental abruption was significantly more common in the Bedouin population. Both populations demonstrated the same annual and seasonal patterns, with higher incidence in spring and autumn.

  10. Malignant cancer and invasive placentation

    PubMed Central

    D'Souza, Alaric W.; Wagner, Günter P.

    2014-01-01

    Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971;47:1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490

  11. Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

    PubMed

    Kwon, T-R; Oh, C T; Park, H M; Han, H J; Ji, H J; Kim, B J

    2015-08-01

    Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans. © 2015 British Association of Dermatologists.

  12. Pathogens and the placental fortress.

    PubMed

    Robbins, Jennifer R; Bakardjiev, Anna I

    2012-02-01

    Placental infections are major causes of maternal and fetal disease. This review introduces a new paradigm for placental infections based on current knowledge of placental defenses and how this barrier can be breached. Transmission of pathogens from mother to fetus can occur at two sites of direct contact between maternal cells and specialized fetal cells (trophoblasts) in the human placenta: firstly, maternal immune and endothelial cells juxtaposed to extravillous trophoblasts in the uterine implantation site and secondly, maternal blood surrounding the syncytiotrophoblast (SYN). Recent findings suggest that the primary vulnerability is in the implantation site. We explore evidence that the placental SYN evolved as a defense against pathogens, and that inflammation-mediated spontaneous abortion may benefit mother and pathogen. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Pathogens and the Placental Fortress

    PubMed Central

    Robbins, Jennifer R.

    2011-01-01

    Summary Placental infections are major causes of maternal and fetal disease. This review introduces a new paradigm for placental infections based on current knowledge of placental defenses and how this barrier can be breached. Transmission of pathogens from mother to fetus can occur at two sites of direct contact between maternal cells and specialized fetal cells (trophoblasts) in the human placenta: (i) maternal immune and endothelial cells juxtaposed to extravillous trophoblasts in the uterine implantation site and (ii) maternal blood surrounding the syncytiotrophoblast. Recent findings suggest that the primary vulnerability is in the implantation site. We explore evidence that the placental syncytiotrophoblast evolved as a defense against pathogens, and that inflammation-mediated spontaneous abortion may benefit mother and pathogen. PMID:22169833

  14. Genomics, biogeography, and the diversification of placental mammals

    PubMed Central

    Wildman, Derek E.; Uddin, Monica; Opazo, Juan C.; Liu, Guozhen; Lefort, Vincent; Guindon, Stephane; Gascuel, Olivier; Grossman, Lawrence I.; Romero, Roberto; Goodman, Morris

    2007-01-01

    Previous molecular analyses of mammalian evolutionary relationships involving a wide range of placental mammalian taxa have been restricted in size from one to two dozen gene loci and have not decisively resolved the basal branching order within Placentalia. Here, on extracting from thousands of gene loci both their coding nucleotide sequences and translated amino acid sequences, we attempt to resolve key uncertainties about the ancient branching pattern of crown placental mammals. Focusing on ≈1,700 conserved gene loci, those that have the more slowly evolving coding sequences, and using maximum-likelihood, Bayesian inference, maximum parsimony, and neighbor-joining (NJ) phylogenetic tree reconstruction methods, we find from almost all results that a clade (the southern Atlantogenata) composed of Afrotheria and Xenarthra is the sister group of all other (the northern Boreoeutheria) crown placental mammals, among boreoeutherians Rodentia groups with Lagomorpha, and the resultant Glires is close to Primates. Only the NJ tree for nucleotide sequences separates Rodentia (murids) first and then Lagomorpha (rabbit) from the other placental mammals. However, this nucleotide NJ tree still depicts Atlantogenata and Boreoeutheria but minus Rodentia and Lagomorpha. Moreover, the NJ tree for amino acid sequences does depict the basal separation to be between Atlantogenata and a Boreoeutheria that includes Rodentia and Lagomorpha. Crown placental mammalian diversification appears to be largely the result of ancient plate tectonic events that allowed time for convergent phenotypes to evolve in the descendant clades. PMID:17728403

  15. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    PubMed

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. © 2016 American Heart Association, Inc.

  16. PLACENTAL GROWTH FACTOR ADMINISTRATION ABOLISHES PLACENTAL ISCHEMIA-INDUCED HYPERTENSION

    PubMed Central

    Spradley, Frank T.; Tan, Adelene Y.; Joo, Woo S.; Daniels, Garrett; Kussie, Paul; Karumanchi, S. Ananth; Granger, Joey P.

    2016-01-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia as placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and VEGF are both natural ligands for sFlt-1, VEGF also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to four groups: normal pregnant (NP) or RUPP ± infusion of rhPlGF (180 μg/kg/day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than NP rats. Infusion of rhPlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that rhPlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  17. Programming placental nutrient transport capacity

    PubMed Central

    Fowden, A L; Ward, J W; Wooding, F P B; Forhead, A J; Constancia, M

    2006-01-01

    Many animal studies and human epidemiological findings have shown that impaired growth in utero is associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over-exposure on placental phenotype with particular emphasis on the role of the Igf2 gene in these processes. PMID:16439433

  18. Placental Adaptations in Growth Restriction

    PubMed Central

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  19. Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1.

    PubMed

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline; Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Spliid, Charlotte; Mathiesen, Line; E Knudsen, Lisbeth; Damm, Peter; G Theander, Thor; R Hansson, Stefan; A Nielsen, Morten; Salanti, Ali

    2016-08-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.

  20. Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1

    PubMed Central

    Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Damm, Peter; G. Theander, Thor; R. Hansson, Stefan; Salanti, Ali

    2016-01-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells. PMID:27556547

  1. Utero-placental Doppler ultrasound for improving pregnancy outcome

    PubMed Central

    Stampalija, Tamara; Gyte, Gillian ML; Alfirevic, Zarko

    2014-01-01

    Background Impaired placentation can cause some of the most important obstetrical complications such as pre-eclampsia and intrauterine growth restriction and has been linked to increased fetal morbidity and mortality. The failure to undergo physiological trophoblastic vascular changes is reflected by the high impedance to the blood flow at the level of the uterine arteries. Doppler ultrasound study of utero-placental blood vessels, using waveform indices or notching, may help to identify the ‘at-risk’ women in the first and second trimester of pregnancy, such that interventions might be used to reduce maternal and fetal morbidity and/or mortality. Objectives To assess the effects on pregnancy outcome, and obstetric practice, of routine utero-placental Doppler ultrasound in first and second trimester of pregnancy in pregnant women at high and low risk of hypertensive complications. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (June 2010) and the reference lists of identified studies. Selection criteria Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of utero-placental vessel waveforms in first and second trimester compared with no Doppler ultrasound. We have excluded studies where uterine vessels have been assessed together with fetal and umbilical vessels. Data collection and analysis Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We checked data entry. Main results We found two studies involving 4993 participants. The methodological quality of the trials was good. Both studies included women at low risk for hypertensive disorders, with Doppler ultrasound of the uterine arteries performed in the second trimester of pregnancy. In both studies, pathological finding of uterine arteries was followed by low-dose aspirin administration. We identified no difference in short-term maternal and fetal clinical

  2. Placental Origins of Chronic Disease

    PubMed Central

    Burton, Graham J.; Fowden, Abigail L.; Thornburg, Kent L.

    2016-01-01

    Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions. PMID:27604528

  3. Placental calcification: a metastatic process?

    PubMed

    Poggi, S H; Bostrom, K I; Demer, L L; Skinner, H C; Koos, B J

    2001-07-01

    Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

  4. Altered fetal growth, placental abnormalities, and stillbirth.

    PubMed

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (<10th percentile) and large (>90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of

  5. Placental membrane aging and HMGB1 signaling associated with human parturition

    PubMed Central

    Menon, Ramkumar; Behnia, Faranak; Polettini, Jossimara; Saade, George R; Campisi, Judith; Velarde, Michael

    2016-01-01

    Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence—the loss of cell division potential as a consequence of stress—is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase, and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition. PMID:26851389

  6. Placental membrane aging and HMGB1 signaling associated with human parturition.

    PubMed

    Menon, Ramkumar; Behnia, Faranak; Polettini, Jossimara; Saade, George R; Campisi, Judith; Velarde, Michael

    2016-02-01

    Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.

  7. Placental pathology measures: Can they be rapidly and reliably integrated into large-scale perinatal studies?

    PubMed

    Catov, J M; Peng, Y; Scifres, C M; Parks, W T

    2015-06-01

    Normal placental function is critical to optimize fetal growth and development, but few perinatal studies incorporate placental measures. Our objectives were to link clinical placental pathology records to birth records, and validate an automated abstraction strategy. Of the 47,329 deliveries at our hospital from 2008 to 2012, we retrieved electronic copies of pathology reports (n = 21,585, 45.4%). Pathology data were extracted with Extensible Markup Language (XML) script using Java and structured query language (SQL) transformed the text information into variables that were linked to delivery data. A subgroup of records was selected for a validation study that compared automated to manual abstraction (n = 144). Linked birth-placental records included 93% of all preterm (<37 weeks, n = 5108) and 37.1% of term births (n = 14,019). Over 90% of deliveries complicated by preeclampsia, chronic hypertension, or gestational diabetes included pathology data. The validation study indicated excellent agreement, sensitivity and specificity between the two abstraction strategies. We demonstrate a reliable approach to electronically integrate placental pathology and delivery data. These linked data provide a platform to identify risk factors and sequelae associated with placental lesions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Chromatofocusing of purified placental sphingomyelinase.

    PubMed

    Rousson, R; Vanier, M T; Louisot, P

    1983-02-01

    To establish the profile of the multiple forms of placental lysosomal sphingomyelinase, we have developed in a preliminary step, a new sequence of purification. This protocol has a good yield such that the final preparation is representative of the whole enzyme. Using chromatofocusing, purified sphingomyelinase is resolved into 4 major forms whose pI's are 7.2, 6.5, 5.9 and 5.2. Chromatofocusing is preferable to isoelectric focusing because it is more rapid, more reproducible and above all it provides a constant profile of activity which is not influenced by experimental conditions, in particular, detergent concentration.

  9. Microparasites and Placental Invasiveness in Eutherian Mammals

    PubMed Central

    Capellini, Isabella; Nunn, Charles L.; Barton, Robert A.

    2015-01-01

    Placental invasiveness—the number of maternal tissue layers separating fetal tissues from maternal blood—is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness. PMID:26168031

  10. Prenatal Diagnosis and Evaluation of Abnormal Placentation.

    PubMed

    Fox, Karin A; Lee, Wesley

    2017-09-01

    Abnormalities in placental location or adherence can have important consequences on pregnancy outcome for both mother and fetus. Accurate antenatal detection is crucial for delivery timing and planning to help reduce perinatal risks for adverse events. We review the relevant literature and present a practical approach for the prenatal detection of abnormal placentation.

  11. Dietary composition programmes placental phenotype in mice.

    PubMed

    Coan, P M; Vaughan, O R; McCarthy, J; Mactier, C; Burton, G J; Constância, M; Fowden, A L

    2011-07-15

    Dietary composition during pregnancy influences fetal and adult phenotype but its effects on placental phenotype remain largely unknown. Using molecular, morphological and functional analyses, placental nutrient transfer capacity was examined in mice fed isocaloric diets containing 23%, 18% or 9% casein (C) during pregnancy. At day 16, placental transfer of glucose, but not methyl-aminoisobutyric acid (MeAIB), was greater in C18 and C9 than C23 mice, in association with increased placental expression of the glucose transporter Slc2a1/GLUT1, and the growth factor Igf2. At day 19, placental glucose transport remained high in C9 mice while MeAIB transfer was less in C18 than C23 mice, despite greater placental weights in C18 and C9 than C23 mice. Placental System A amino acid transporter expression correlated with protein intake at day 19. Relative growth of transport verses endocrine zones of the placenta was influenced by diet at both ages without changing the absolute volume of the transport surface. Fetal weight was unaffected by diet at day 16 but was reduced in C9 animals by day 19. Morphological and functional adaptations in placental phenotype, therefore, occur to optimise nutrient transfer when dietary composition is varied, even subtly. This has important implications for the intrauterine programming of life expectancy.

  12. Nomenclature and placental mammal phylogeny

    PubMed Central

    2010-01-01

    An issue arising from recent progress in establishing the placental mammal Tree of Life concerns the nomenclature of high-level clades. Fortunately, there are now several well-supported clades among extant mammals that require unambiguous, stable names. Although the International Code of Zoological Nomenclature does not apply above the Linnean rank of family, and while consensus on the adoption of competing systems of nomenclature does not yet exist, there is a clear, historical basis upon which to arbitrate among competing names for high-level mammalian clades. Here, we recommend application of the principles of priority and stability, as laid down by G.G. Simpson in 1945, to discriminate among proposed names for high-level taxa. We apply these principles to specific cases among placental mammals with broad relevance for taxonomy, and close with particular emphasis on the Afrotherian family Tenrecidae. We conclude that no matter how reconstructions of the Tree of Life change in years to come, systematists should apply new names reluctantly, deferring to those already published and maximizing consistency with existing nomenclature. PMID:20406454

  13. Intracellular Organisms as Placental Invaders

    PubMed Central

    Vigliani, Marguerite B.; Bakardjiev, Anna I.

    2015-01-01

    In this article we present a novel model for how the human placenta might get infected via the hematogenous route. We present a list of diverse placental pathogens, like Listeria monocytogenes or Cytomegalovirus, which are familiar to most obstetricians, but others, like Salmonella typhi, have only been reported in case studies or small case series. Remarkably, all of these organisms on this list are either obligate or facultative intracellular organisms. These pathogens are able to enter and survive inside host immune cells for at least a portion of their life cycle. We suggest that many blood-borne pathogens might arrive at the placenta via transportation inside of maternal leukocytes that enter the decidua in early pregnancy. We discuss mechanisms by which extravillous trophoblasts could get infected in the decidua and spread infection to other layers in the placenta. We hope to raise awareness among OB/GYN clinicians that organisms not typically associated with the TORCH list might cause placental infections and pregnancy complications. PMID:27695204

  14. l-Methionine Placental Uptake

    PubMed Central

    Araújo, João R.; Correia-Branco, Ana; Ramalho, Carla; Gonçalves, Pedro; Pinho, Maria J.; Keating, Elisa

    2013-01-01

    Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process. PMID:23653387

  15. Altered fetal growth, placental abnormalities, and stillbirth

    PubMed Central

    Bukowski, Radek; Hansen, Nellie I.; Pinar, Halit; Willinger, Marian; Reddy, Uma M.; Parker, Corette B.; Silver, Robert M.; Dudley, Donald J.; Stoll, Barbara J.; Saade, George R.; Koch, Matthew A.; Hogue, Carol; Varner, Michael W.; Conway, Deborah L.; Coustan, Donald; Goldenberg, Robert L.

    2017-01-01

    Background Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Methods and findings Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (<10th percentile) and large (>90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner

  16. The evolution of epitheliochorial placentation.

    PubMed

    Carter, Anthony M; Enders, Allen C

    2013-01-01

    Epitheliochorial placentation is a derived condition and has evolved separately in strepsirrhine primates and laurasiatherians (pangolins, whales, and hoofed mammals). Usually it is associated with a long gestation period, small litters, and precocial young. Oxygen transfer is facilitated by indenting of the uterine and trophoblast epithelia by maternal and fetal capillaries, respectively. Histotrophic nutrition is important, and adaptations include areolas and hemophagous regions. In pigs and horses, for example, iron is transported as uteroferrin secreted from the uterine glands and taken up by areolas. In the horse, invasive trophoblast cells form cups within the endometrium that are the source of equine chorionic gonadotropin. In ruminants, binucleate trophoblast cells fuse with uterine epithelial cells to form trinucleate cells or plaques that secrete pregnancy hormones. There is evidence of immunosuppression in connection with these more invasive types of trophoblasts. The epitheliochorial condition may be advantageous for long pregnancies in large animals.

  17. Activin A, corticotropin-releasing factor and prostaglandin F2 alpha increase immunoreactive oxytocin release from cultured human placental cells.

    PubMed

    Florio, P; Lombardo, M; Gallo, R; Di Carlo, C; Sutton, S; Genazzani, A R; Petraglia, F

    1996-01-01

    The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n = 5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48-72 h after dissociation, the effect of arginine vasopressin, corticotropin-releasing factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of corticotropin-releasing factor or arginine vasopressin, but not of neuropeptide Y, increased the release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P < 0.01). A significantly increased release of immunoreactive oxytocin was shown in presence of noradrenaline (P < 0.01), which was reversed by prazosin, an antagonist of alpha-adrenergic receptors. Recombinant human activin A (P < 0.01), but not inhibin A, stimulated the release of immunoreactive oxytocin three- to fourfold from placental cells. Prostaglandin F2 alpha was a potent secretagogue of immunoreactive oxytocin, whereas a partial or no effect was observed when prostaglandin E2 or prostaglandin I2 was added. Thus, the present findings showed that human placenta contains immunoreactive oxytocin, and that its release from cultured placental cells is regulated by neurohormones, growth factors or prostaglandins.

  18. Placental hypoxia: the lesions of maternal malperfusion.

    PubMed

    Parks, W Tony

    2015-02-01

    The placental lesions classically ascribed to placental hypoxia, here denoted maternal malperfusion (MMP), are among the more significant that a placental pathologist may encounter. Yet the appearance of these lesions may be subtle, and the clinical implication of their diagnosis is frequently unclear. The aim of this review is to provide a more nuanced perspective on the clinical utility of placental pathology for the detection of MMP. The review will first detail MMP lesions in the placenta and discuss their associations with pregnancy complications. The review will then delve into the diagnostic and interpretive difficulties of these lesions. Finally, recent research findings that may aid in the development of better diagnostic tools will be briefly discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Placental immaturity, endocardial fibroelastosis and fetal hypoxia.

    PubMed

    Perez, Marie-Hélène; Boulos, Tatiana; Stucki, Pascal; Cotting, Jacques; Osterheld, Maria-Chiara; Di Bernardo, Stefano

    2009-01-01

    We describe a term newborn who, after a normal gestational course, presented at birth with absent cardiac activity and no spontaneous breathing. Death occurred within 30 h. Autopsy revealed placental villous immaturity, multiple acute hypoxic lesions, but also chronic hypoxic lesions like endocardial fibroelastosis. This striking association of endocardial fibroelastosis and placental villous immaturity is reviewed and correlated with 2 other cases of placental villous immaturity that led to in utero death at 39 and 41 weeks of gestation. Placental villous immaturity must be suspected and looked for by both pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia of unclear origin. In order to minimize the risk of recurrence in further pregnancies, elective cesarean section may be considered.

  20. Comparative aspects of trophoblast development and placentation

    PubMed Central

    Carter, Anthony M; Enders, Allen C

    2004-01-01

    Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it evolved twice, once in the

  1. Comparative aspects of trophoblast development and placentation.

    PubMed

    Carter, Anthony M; Enders, Allen C

    2004-07-05

    Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it evolved twice, once in the

  2. Evidence of Placental Hemorrhage and Preterm Delivery

    PubMed Central

    Gargano, Julia Warner; Holzman, Claudia B.; Senagore, Patricia K.; Reuss, M. Lynne; Pathak, Dorothy R.; Williams, Michelle A.; Fisher, Rachel

    2011-01-01

    Objective to evaluate evidence of placental hemorrhage (PH) obtained through maternal interviews, patient charts, and placental pathology examinations as potential indicators of a “bleeding pathway” to preterm delivery (PTD). Design Prospective cohort Setting Fifty-two clinics in five communities in Michigan, USA (1998–2004) Population A subset (N=996) of cohort participants with complete placental pathology data Methods First trimester bleeding and placental abruption were ascertained by mid-trimester interviews and chart review, respectively. Disc-impacting blood clot was defined as a gross placental examination finding of a blood clot impacting adjacent tissue. Microscopic hemorrhage was defined as “high” (top quintile) scores on an aggregate measure of placental pathology findings suggestive of atypical maternal vessel hemorrhage. These four PH indicators were compared with one another and with risk of PTD assessed by logistic regression analyses. Main Outcome Measures PTD and PTD subtypes (i.e., <35 weeks, 35–36 weeks; spontaneous, medically indicated) compared with term deliveries. Results Placental abruption cases had 2.3 to 5.5-fold increased odds of the other 3 PH indicators. Disc-impacting blood clots and microscopic hemorrhage were associated with one another (OR=4.6), but not with first trimester bleeding. In a multivariable model that included all four PH indicators and confounders, risk of PTD <35 weeks was elevated with first trimester bleeding (OR=1.9 (1.0, 3.4)), placental abruption (OR=5.2 (1.7, 16.2)), disc-impacting blood clots (OR=2.3 (1.0, 5.0)); and microscopic hemorrhage (OR=2.4 (1.4, 4.2)). Conclusions Multiple clinical and subclinical PH indicators are associated with PTD, particularly early PTD. PMID:20074262

  3. The distinct proteome of placental malaria parasites.

    SciTech Connect

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  4. Protracted induction of parturition enhances placental maturation, but does not influence incidence of placental retention in cows.

    PubMed

    Hartmann, D; Bollwein, H; Honnens, A; Niemann, H; Rath, D; Pfarrer, C

    2013-08-01

    As the etiopathology of retained placenta is still not resolved in cattle, we compared the effects of protracted induction of parturition (PIP) and conventional induction of parturition (SIP) on placental maturation and the occurrence of retained placenta. PIP was induced in 13 cows by administration of 1.3 mg dexamethasone im twice daily between Days 268 and 273 of gestation and 40 mg dexamethasone im on Day 274 of gestation. For SIP, 10 cows received a single injection of 40 mg dexamethasone on Day 274 of gestation. A third group (SPON, n = 11) served as a nontreated control group. Within 2 hours after birth, two placentomes were extracted from the uterus and used for assessment of placental maturation by histology and immunohistochemistry. Incidence of retained placenta was lower (P < 0.05) in group SPON (9%) compared with groups PIP (54%) and SIP (70%). Staining with Masson's trichrome and pan-cytokeratin indicated a higher degree of atrophy and flatness of the maternal crypt epithelium in cows with physiological release of fetal membranes (REL) compared with cows with retained placentae (RET). Staining with anti-caspase-3 ratified the observations as more apoptotic cells were detected in groups SPON and PIP compared with group SIP; however, data were not statistically significant. Additionally, the expressions of the potent vasodilators endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were evaluated. Both eNOS and iNOS were only expressed in chorionic tissue. Endothelin-1 (ET-1), a major vasoconstrictor, showed positive staining in maternal crypt epithelium and in chorionic epithelium. No differences were found for iNOS and eNOS and ET-1, neither among the experimental groups nor between RET and REL cows. These findings indicate that a PIP results in increased placental maturation, but does not influence the incidence of placental retention in cows. The expression of vasoactive substances does not seem to be related to the

  5. Placental pericytes and cytomegalovirus infectivity: Implications for HCMV placental pathology and congenital disease.

    PubMed

    Aronoff, David M; Correa, Hernan; Rogers, Lisa M; Arav-Boger, Ravit; Alcendor, Donald J

    2017-09-01

    Placental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown. HCMV-infected placental tissue was stained by dual-labeled immunohistochemistry. Primary placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to HCMV; and infectivity was analyzed by microscopy and immunofluorescence. Cytokine expression was examined by Luminex assay. A HCMV-GFP recombinant virus was used to examine replication kinetics. Immunohistochemistry showed HCMV in trophoblast and the villous core with T-cell and macrophage infiltration. Primary HCMV isolate from a patient (SBCMV)- infected pericytes showed dysregulation of proinflammatory and angiogenic cytokines when compared to control cells. A tri-cell model of the villous floor showed a unique expression profile. Finally, we show pericytes infected in vivo with HCMV in placental tissue from a congenitally infected child. Placental pericytes support HCMV replication, inducing proinflammatory and angiogenic cytokines that likely contribute to viral dissemination, placenta inflammation, and dysregulation of placental angiogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Placental steroid hormone biosynthesis in primate pregnancy.

    PubMed

    Albrecht, E D; Pepe, G J

    1990-02-01

    Substantial advances in our understanding of placental function have resulted from recent establishment of in vitro approaches, such as cell culture, and application of molecular methods to study placental steroidogenesis. Insight into the processes of placental cell differentiation and hormonal function has been gained from culture of relatively pure preparations of cytotrophoblast. Various factors, e.g. cAMP and peptide growth factors, have been shown to have striking effects on progesterone and estrogen formation by placental tissue under in vitro conditions. Using advanced molecular approaches, the genes governing specific enzymes critical to placental steroidogenesis have been identified. Regulation of the mRNAs encoding specific enzyme peptides and thus expression of the genes by factors, such as cAMP, have been elucidated by Northern analysis and other techniques. It is critical that these contemporary approaches continue to be implemented aggressively to further elucidate placental function. However, it is clear from a survey of the literature, particularly of the past decade, that the vast majority of investigation in the area has been conducted in vitro. It is essential to determine whether the factors that have been observed to regulate placental endocrine function in vitro are operable in vivo. It is only with in vivo study that the dynamics of steroidogenesis and the complex functional relationships between placenta, fetus, and mother will be uncovered and understood. It is increasingly evident that the regulation of placental steroidogenesis involves autocrine and/or paracrine mechanisms, similar to those integral to hormone biosynthesis within other reproductive organs, e.g. ovary and testis. For example, as discussed above, estrogen regulates LDL uptake and P-450scc, and thus apparently is involved in generating substrate for progesterone production within the placenta. Conversely, progesterone has effects on 17 beta-hydroxysteroid oxidoreductase

  7. Impaired placentation in fetal alcohol syndrome.

    PubMed

    Gundogan, F; Elwood, G; Longato, L; Tong, M; Feijoo, A; Carlson, R I; Wands, J R; de la Monte, S M

    2008-02-01

    Intrauterine growth restriction (IUGR) is one of the key features of fetal alcohol syndrome (FAS), and IUGR can be mediated by impaired placentation. Insulin-like growth factors (IGF) regulate placentation due to stimulatory effects on extravillous trophoblasts, which are highly motile and invasive. Previous studies demonstrated that extravillous trophoblasts express high levels of aspartyl-(asparaginyl) beta-hydroxylase (AAH), a gene that is regulated by IGF and has a critical role in cell motility and invasion. The present study examines the hypothesis that ethanol impaired placentation is associated with inhibition of AAH expression in trophoblasts. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 37% ethanol by caloric content. Placentas harvested on gestation day 16 were used for histopathological, mRNA, and protein studies to examine AAH expression in relation to the integrity of placentation and ethanol exposure. Chronic ethanol feeding prevented or impaired the physiological conversion of uterine vessels required for expansion of maternal circulation into placenta, a crucial process for adequate placentation. Real-time quantitative RT-PCR analysis demonstrated significant reductions in IRS-1, IRS-2, and significant increases in IGF-II and IGF-II receptor mRNA levels in ethanol-exposed placentas. These abnormalities were associated with significantly reduced levels of AAH expression in trophoblastic cells, particularly within the mesometrial triangle (deep placental bed) as demonstrated by real time quantitative RT-PCR, Western blot analysis, ELISA, and immunohistochemical staining. Ethanol-impaired placentation is associated with inhibition of AAH expression in trophoblasts. This effect of chronic gestational exposure to ethanol may contribute to IUGR in FAS.

  8. A quality system for placental blood banking.

    PubMed

    Sirchia, G; Rebulla, P; Mozzi, F; Lecchi, L; Lazzari, L; Ratti, I

    1998-06-01

    A Quality System for Placental Blood Banking aimed at the transplantation of haematopoietic stem cells to related and unrelated allogeneic recipients is described. It includes the organizational structure, procedures, processes and resources needed to implement quality management. The Quality System described in this article is based on ISO 9002, a model for quality assurance in production, installation and servicing developed in 1987 and revised in 1994 by the International Organization for Standardization. ISO 9002 includes 20 clauses that provide guidance for the implementation of the Quality System. The development of the Quality System is started by the Placental Blood Bank Medical Director with the definition of a General Quality Plan including: (1) the written description of the Mission, Objectives, Technical and Organizational Policies, and Staff Organization Chart; (2) the definition and acquisition of adequate financial, human and structural resources; (3) the appointment of a Quality System Head, who must identify the Placental Blood Banking process together with the Placental Blood Bank personnel; implement a documentation plan; identify quality indicators; start regular internal audit; report audit results to the Medical Director for review. Following staff training and qualification, the Quality System is launched. The Placental Blood Bank can then undergo audit by an external inspector and be finally certified for compliance to ISO 9002. The Quality System must be maintained and subjected to external audit at regular intervals so that certification is confirmed.

  9. 21 CFR 862.1585 - Human placental lactogen test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... placental lactogen are used in the diagnosis and clinical management of high-risk pregnancies involving fetal distress associated with placental insufficiency. Measurements of HPL are also used in pregnancies...

  10. 21 CFR 862.1585 - Human placental lactogen test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... placental lactogen are used in the diagnosis and clinical management of high-risk pregnancies involving fetal distress associated with placental insufficiency. Measurements of HPL are also used in pregnancies...

  11. 21 CFR 862.1585 - Human placental lactogen test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... placental lactogen are used in the diagnosis and clinical management of high-risk pregnancies involving fetal distress associated with placental insufficiency. Measurements of HPL are also used in pregnancies...

  12. 21 CFR 862.1585 - Human placental lactogen test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... placental lactogen are used in the diagnosis and clinical management of high-risk pregnancies involving fetal distress associated with placental insufficiency. Measurements of HPL are also used in pregnancies...

  13. Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia.

    PubMed

    Liao, Wu-Xiang; Laurent, Louise C; Agent, Sally; Hodges, Jennifer; Chen, Dong-Bao

    2012-04-01

    Preeclampsia is characterized by dysfunctional endothelium and impaired angiogenesis. Recent studies suggest that the neuronal guidance SLIT/ROBO system regulates tumor angiogenesis. This study investigated if SLIT and ROBO are differentially expressed in healthy term and preeclamptic placentas and if hypoxia regulates SLIT and ROBO expression in placental trophoblast and endothelial cells. Total RNA and protein were extracted from placental tissues of healthy term (n = 5) and preeclamptic (n = 6) pregnancies and used for SLIT/ROBO expression analyses with reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative-PCR, and immunoblotting. Paraffin-embedded tissues were processed to localize SLIT/ROBO proteins in placental villi by immunohistochemistry. BeWo choriocarcinoma cells and human umbilical vein endothelial cells (HUVEC) were treated with 2% or 10% oxygen or the hypoxia mimetic deferoxamine mesylate (100 μM) to test if hypoxia regulates SLIT/ROBO expression. SLIT2, SLIT3, ROBO1, and ROBO4 mRNA and proteins were detected in the placenta. SLIT2 and ROBO1 proteins localized in the syncytiotrophoblast, and SLIT3, ROBO1, and ROBO4 in capillary endothelium of the placental villi. Levels of ROBO1 and ROBO4 as well as sFLT1 (soluble fms-like tyrosine kinase-1) proteins were significantly greater in preeclamptic placentas compared to normal controls. Hypoxia significantly increased both mRNA and protein levels of SLIT2 in BeWo cells and of SLIT3, ROBO1, and ROBB4 in HUVEC. Thus, trophoblast and endothelial coexpression of SLIT/ROBO suggests an autocrine/paracrine regulatory system for regulating placental function. Differential expression of SLITs and ROBOs in healthy term and preeclamptic placentas and hypoxia regulation of their expressions in placental cells implicate a potential pathophysiological role for this system in preeclampsia.

  14. Associations between maternal level of education and occupational status with placental glucocorticoid regeneration and sensitivity.

    PubMed

    Räikkönen, Katri; O'Reilly, James R; Pesonen, Anu-Katriina; Kajantie, Eero; Villa, Pia; Laivuori, Hannele; Hämäläinen, Esa; Seckl, Jonathan R; Reynolds, Rebecca M

    2014-08-01

    Low socio-economic status (SES) is associated with increased disease risk in the involved and the next generation. The effects of low maternal SES on the offspring may be initiated prenatally. We hypothesized that fetoplacental glucocorticoid exposure might mediate the links. We examined associations between maternal level of education and occupational status (used as indices of SES) and placental expression of genes involved in glucocorticoid exposure and transfer between the mother and foetus. Placental biopsies were obtained from 67 healthy women (age 32.2 ± 5.3 years) with singleton, term pregnancies without obstetric complications who participated in a prospective Prediction and Prevention of Preeclampsia (PREDO) study. Level of education was self-reported, and occupational status was extracted from hospital records. Relative glucocorticoid receptor (GR; NR3C1), mineralocorticoid receptor (MR; NR3C2) and 11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2) mRNA levels were quantified by real-time PCR. Placental GR and HSD11B1 expression increased with decreasing maternal education (unadjusted P-values for linear trend = 0.04 and 0.02 and adjusted P-values = 0.06 and 0.09, respectively). Mothers with primary/secondary education had 52.9% (95% CI, 6.2-99.6, P = 0.03, adjusted P = 0.05) and 79.6% (95% CI, 6.5-153.6, P = 0.03, adjusted P = 0.09) higher GR and HSD11B1 mRNA levels compared with mothers with tertiary education. There were no other significant associations. Lower maternal level of education is associated with increased placental GR and HSD11B1 gene expression. This combination may regenerate active glucocorticoids in placenta and increase placental sensitivity to glucocorticoids, potentially leading to greater placental and foetal glucocorticoid exposure. © 2014 John Wiley & Sons Ltd.

  15. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

    PubMed Central

    Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome. PMID:27186326

  16. PPAR Signaling in Placental Development and Function.

    PubMed

    Barak, Yaacov; Sadovsky, Yoel; Shalom-Barak, Tali

    2008-01-01

    With the major attention to the pivotal roles of PPARs in diverse aspects of energy metabolism, the essential functions of PPARgamma and PPARbeta/delta in placental development came as a surprise and were often considered a nuisance en route to their genetic analysis. However, these findings provided an opportune entrée into placental biology. Genetic and pharmacological studies, primarily of knockout animal models and cell culture, uncovered networks of PPARgamma and PPARdelta, their heterodimeric RXR partners, associated transcriptional coactivators, and target genes, that regulate various aspects of placental development and function. These studies furnish both specific information about trophoblasts and the placenta and potential hints about the functions of PPARs in other tissues and cell types. They reveal that the remarkable versatility of PPARs extends beyond the orchestration of metabolism to the regulation of cellular differentiation, tissue development, and trophoblast-specific functions. This information and its implications are the subject of this review.

  17. 21 CFR 862.1585 - Human placental lactogen test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human placental lactogen test system. 862.1585 Section 862.1585 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1585 Human placental lactogen test system. (a) Identification. A human placental...

  18. Placental Gas Exchange and the Oxygen Supply to the Fetus.

    PubMed

    Carter, Anthony M

    2015-07-01

    The oxygen supply of the fetus depends on the blood oxygen content and flow rate in the uterine and umbilical arteries and the diffusing capacity of the placenta. Oxygen consumption by the placenta is a significant factor and a potential limitation on availability to the fetus. The relevance of these several factors as well as responses to acute or sustained hypoxia has been explored in the sheep model. In addition, much has been learned in the context of hypobaric hypoxia by studying human populations that have resided at high altitude for varying periods of time. Embryonic development occurs under anaerobic conditions and even the fetus is adapted to a low oxygen environment. Nevertheless, there is a reserve capacity, and during acute hypoxia the fetus can counter a 50% reduction in oxygen delivery by increasing fractional extraction. During sustained hypoxia, on the other hand, fetal growth is slowed, although oxygen consumption is unaltered when corrected for fetal mass. Similarly, birth weight is reduced in humans living at high altitude even if the effect is tempered in those with a long highland ancestry. Placental mass changes little during sustained hypoxia in sheep or humans at high altitude. This conceals the fact that there are structural changes and that placental oxygen consumption is reduced. The underlying mechanisms are a current focus of research. One intriguing possibility is that increased anaerobic metabolism of glucose in the placenta spares oxygen for the fetus but reduces its supply of substrate and thereby limits fetal growth.

  19. Placental proteome alterations in women with intrahepatic cholestasis of pregnancy.

    PubMed

    He, Pei; Wang, Furong; Jiang, Yan; Zhong, Yi; Lan, Yongfei; Chen, Shuqing

    2014-09-01

    To investigate differences in the placental proteomes of women with intrahepatic cholestasis of pregnancy (ICP) and those with a normal pregnancy. Ten pregnant women diagnosed with ICP were recruited at the First People's Hospital of Yuhang District from October 2011 to September 2012; 10 age-matched healthy pregnant women acted as controls. Total placental proteins were extracted and subjected to two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry to identify proteins that were differentially expressed in the two groups. In total, 37 protein spots with differentially expressed proteins were found. These comprised proteins involved in cytoskeleton activity, blood coagulation, and platelet activation as well as chaperones, heat shock proteins, RNA-binding and calcium-binding proteins, and various enzymes. The placentas of women with ICP displayed significant proteome differences compared with women with a normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of ICP. Further verification and research are required to elucidate the exact roles of these proteins in ICP pathogenesis. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Fetal-placental and decidual-placental units: role of endocrine and paracrine regulations in parturition.

    PubMed

    Carbillon, L; Uzan, M; Challier, J C; Merviel, P; Uzan, S

    2000-01-01

    In primates, fetal adrenal and placental steroidogenic enzymatic systems are complementary in a fetal-placental unit, synchronizing fetal maturation and myometrial activation in late gestation. Moreover, as hemochorial placentation characterizes rodents and primates, paracrine regulations between decidua and placenta are essential to the immunotolerance of the conceptus and its development. Thus, the decidual-placental unit remains in a striking state of decidual quiescence throughout gestation, and the reversal of this quiescence is thought to play a key role in myometrial stimulation and the onset of parturition. A comprehensive view of the control of myometrial contractility, through the interaction of paracrine and endocrine modifications in late gestation, is proposed. The failure of these mechanisms underlie prematurity and the use of fetal therapy in threatened preterm labor. Copyright 2000 S. Karger AG, Basel.

  1. Relation between utero-placental and feto-placental circulations: a longitudinal study.

    PubMed

    Flo, Kari; Wilsgaard, Tom; Acharya, Ganesh

    2010-10-01

    To explore the relation between total utero-placental (TQ(uta)) and feto-placental (Q(uv)) blood flows and establish longitudinal reference ranges for the TQ(uta)/Q(uv) ratio and the mean uterine artery and umbilical artery pulsatility (UtaPI/UAPI) and resistance index (UtaRI/UARI) ratios. Prospective longitudinal observational study. University hospital in Norway. Fifty-three low-risk pregnant women. Uterine artery and umbilical vein blood flow was measured using Doppler ultrasonography at 4-weekly intervals from 22(+0) to 39(+6) weeks of gestation. Ratios between utero-placental and feto-placental volume blood flows and between indices of uterine and umbilical artery impedance. The TQ(uta)/Q(uv) ratio had a significant association with the gestational age (p < 0.00001) and decreased with advancing gestation during the second half of pregnancy. The mean UtaPI/UAPI (p = 0.094) and mean UtaRI/UARI (p = 0.323) ratios were not significantly associated with gestational age and remained relatively constant. There was no significant association between TQ(uta) and Q(uv) (p = 0.72), mean UtaPI and UAPI (p = 0.56), or mean UtaRI and UARI (p = 0.57). The gestational-age-related changes in the utero-placental and feto-placental circulations do not appear to be affected by each other under physiological conditions. We have established longitudinal reference ranges for the utero-placental and feto-placental blood flow and impedance ratios during the second half of pregnancy.

  2. Placental Nutrient Transport and Intrauterine Growth Restriction

    PubMed Central

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as maternal undernutrition, pre-eclampsia, young maternal age, high altitude and infection. PMID:26909042

  3. BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION

    EPA Science Inventory

    BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL
    TROPHOBLAST DIFFERENTIATION
    Jiangang Chen, Twanda L. Thirkill, Peter N. Lohstroh, Susan R. Bielmeier, Michael
    G. Narotsky, Deborah S. Best, Randy A. Harrison, Kala Natarajan, Rex A. Pegram,
    Bill L. Lasley, and Gordon C. Do...

  4. BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION

    EPA Science Inventory

    BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL
    TROPHOBLAST DIFFERENTIATION
    Jiangang Chen, Twanda L. Thirkill, Peter N. Lohstroh, Susan R. Bielmeier, Michael
    G. Narotsky, Deborah S. Best, Randy A. Harrison, Kala Natarajan, Rex A. Pegram,
    Bill L. Lasley, and Gordon C. Do...

  5. Placental specializations in lecithotrophic viviparous squamate reptiles.

    PubMed

    Stewart, James R

    2015-09-01

    Squamate reptiles have been thought to be predisposed to evolution of viviparity because embryos of most oviparous species undergo considerable development in the uterus prior to oviposition. A related hypothesis proposes that prolonged intrauterine gestation, an intermediate condition leading to viviparity, requires little or no physiological adjustment, other than reduction in thickness of the eggshell. This logical framework is often accompanied by an assumption that mode of parity (oviparity, viviparity) and pattern of embryonic nutrition (lecithotrophy, placentotrophy) are independent traits that evolve in sequence. Thus, specializations for viviparity should be absent in some lecithotrophic viviparous species. Studies of species of lizards with geographic variation in mode of parity challenge this scenario by demonstrating that placental specializations are correlated with viviparity. Uterine specializations for placental transport of calcium to viviparous embryos alter uterine physiology compared to oviparous females. In addition, comparative studies of oviparous and viviparous species, i.e., in which gene flow is disrupted, reveal that both uterine and embryonic structural modifications are commonly associated with viviparity, suggesting relatively rapid evolution of placental specializations. Studies of squamate reproductive biology support two hypotheses: 1) evolution of viviparity requires physiological adjustments of the uterine environment, and 2) evolution of viviparity promotes relatively rapid adaptations for placentation. Models for the evolution of viviparity from oviparity, or for reversals from viviparity to oviparity, should reflect current understanding of squamate reproductive biology and future studies should be designed to challenge these models.

  6. Reduced placental volume and flow in severe growth restricted fetuses

    PubMed Central

    Abulé, Renata Montes Dourado; Bernardes, Lisandra Stein; Doro, Giovana Farina; Miyadahira, Seizo; Francisco, Rossana Pulcinelli Vieira

    2016-01-01

    OBJECTIVES: To evaluate placental volume and vascular indices in pregnancies with severe fetal growth restriction and determine their correlations to normal reference ranges and Doppler velocimetry results of uterine and umbilical arteries. METHODS: Twenty-seven fetuses with estimated weights below the 3rd percentile for gestational age were evaluated. Placental volume and vascular indices, including vascularization, flow, and vascularization flow indices, were measured by three-dimensional ultrasound using a rotational technique and compared to a previously described nomogram. The observed-to-expected placental volume ratio for gestational age and observed-to-expected placental volume ratio for fetal weight were calculated. Placental parameters correlated with the Doppler velocimetry results of uterine and umbilical arteries. RESULTS: The mean uterine artery pulsatility index was negatively correlated with the observed-to-expected placental volume ratio for gestational age, vascularization index and vascularization flow index. The observed-to-expected placental volume ratio for gestational age and observed-to-expected placental volume ratio for fetal weight and vascularization index were significantly lower in the group with a bilateral protodiastolic notch. No placental parameter correlated with the umbilical artery pulsatility index. CONCLUSIONS: Pregnancies complicated by severe fetal growth restriction are associated with reduced placental volume and vascularization. These findings are related to changes in uterine artery Doppler velocimetry. Future studies on managing severe fetal growth restriction should focus on combined results of placental three-dimensional ultrasound and Doppler studies of uterine arteries. PMID:27438567

  7. Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction

    PubMed Central

    Wookey, Alice F.; Chollangi, Tejasvy; Yong, Hannah E. J.

    2017-01-01

    Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic (n = 9) and nonidiopathic (n = 9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, p < 0.05, Student's t-test) that were strongly associated with idiopathic fetal growth restriction (p < 0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores (p = 0.295, Pearson's correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease. PMID:28293436

  8. Osteopontin: roles in implantation and placentation.

    PubMed

    Johnson, Greg A; Burghardt, Robert C; Bazer, Fuller W; Spencer, Thomas E

    2003-11-01

    Osteopontin (OPN) is an acidic member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of extracellular matrix proteins/cytokines that undergoes extensive posttranslational modification, including phosphorylation, glycosylation, and cleavage, yielding molecular mass variants ranging in size from 25 to 75 kDa. The result is a versatile protein(s) with multiple functions arising from its role as a mediator of cell-cell and cell-extracellular matrix (ECM) communication that encompass both normal and tumorigenic developmental processes, immunological responses during inflammation and wound healing, and biomineralization. Studies in primates, pigs, sheep, and rodents have revealed that OPN is a major constituent of the uterine-placental microenvironment with influence as 1) a component of histotroph required for adhesion and signal transduction at the uterine-placental interface throughout pregnancy, 2) a gene product expressed by uterine stroma contributing to a decidualization-like transformation that correlates with the degree of conceptus invasiveness, and 3) a product of resident uterine and placental immune cells that may regulate their behavior and cytokine production. This minireview summarizes information regarding uterine and placental expression of OPN that has accumulated over the past 15 yr, and we briefly describe structural/functional properties of this protein that are likely relevant to its role(s) during pregnancy. Comparative studies have offered insights into the potential hormonal/cytokine, cellular, and molecular mechanisms underlying OPN-mediated adhesion, remodeling, and cell-cell/cell-ECM communication within the uterus and placenta. OPN has the potential to profoundly impact pregnancy, and investigators are now challenged to focus on the mechanistic nature of the functions of this multifaceted and major component of the uterine-placental microenvironment.

  9. Resolving the relationships of Paleocene placental mammals.

    PubMed

    Halliday, Thomas J D; Upchurch, Paul; Goswami, Anjali

    2017-02-01

    The 'Age of Mammals' began in the Paleocene epoch, the 10 million year interval immediately following the Cretaceous-Palaeogene mass extinction. The apparently rapid shift in mammalian ecomorphs from small, largely insectivorous forms to many small-to-large-bodied, diverse taxa has driven a hypothesis that the end-Cretaceous heralded an adaptive radiation in placental mammal evolution. However, the affinities of most Paleocene mammals have remained unresolved, despite significant advances in understanding the relationships of the extant orders, hindering efforts to reconstruct robustly the origin and early evolution of placental mammals. Here we present the largest cladistic analysis of Paleocene placentals to date, from a data matrix including 177 taxa (130 of which are Palaeogene) and 680 morphological characters. We improve the resolution of the relationships of several enigmatic Paleocene clades, including families of 'condylarths'. Protungulatum is resolved as a stem eutherian, meaning that no crown-placental mammal unambiguously pre-dates the Cretaceous-Palaeogene boundary. Our results support an Atlantogenata-Boreoeutheria split at the root of crown Placentalia, the presence of phenacodontids as closest relatives of Perissodactyla, the validity of Euungulata, and the placement of Arctocyonidae close to Carnivora. Periptychidae and Pantodonta are resolved as sister taxa, Leptictida and Cimolestidae are found to be stem eutherians, and Hyopsodontidae is highly polyphyletic. The inclusion of Paleocene taxa in a placental phylogeny alters interpretations of relationships and key events in mammalian evolutionary history. Paleocene mammals are an essential source of data for understanding fully the biotic dynamics associated with the end-Cretaceous mass extinction. The relationships presented here mark a critical first step towards accurate reconstruction of this important interval in the evolution of the modern fauna.

  10. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

    PubMed

    Day, Pricilla E; Ntani, Georgia; Crozier, Sarah R; Mahon, Pam A; Inskip, Hazel M; Cooper, Cyrus; Harvey, Nicholas C; Godfrey, Keith M; Hanson, Mark A; Lewis, Rohan M; Cleal, Jane K

    2015-01-01

    Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

  11. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport

    PubMed Central

    Day, Pricilla E.; Ntani, Georgia; Crozier, Sarah R.; Mahon, Pam A.; Inskip, Hazel M.; Cooper, Cyrus; Harvey, Nicholas C.; Godfrey, Keith M.; Hanson, Mark A.; Lewis, Rohan M.; Cleal, Jane K.

    2015-01-01

    Introduction Maternal environment and lifestyle factors may modify placental function to match the mother’s capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. Methods RNA was extracted from 102 term Southampton Women’s Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Results Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). Conclusion A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter

  12. Cigarette Smoke-Induced Placental Adrenomedullin Expression and Trophoblast Cell Invasion

    PubMed Central

    Kraus, Daniel M.; Feng, Liping; Heine, R. Phillips; Brown, Haywood L.; Caron, Kathleen M.; Murtha, Amy P.

    2014-01-01

    Smoking in pregnancy reduces preeclampsia risk, but the mechanism of this effect is unknown. Prior studies have demonstrated that women with preeclampsia have lower placental adrenomedullin (AM) expression, and cigarette smoke extract (CSE) treatment of placental trophoblast cells in culture increases AM cellular production. We hypothesized that CSE alters trophoblast invasion through an AM-mediated mechanism, and that placental AM expression is greater among smokers. HTR-8/SVneo trophoblast cells were incubated for 24 hours in Matrigel-invasion chambers with 6 treatment groups: nonstimulated (NS), AM, AM inhibitor (AM22-52), 1% CSE, AM + AM22-52, and 1% CSE + AM22-52. Cells that penetrated the lower surface of the chambers were quantified, invasion indices were calculated, and compared using a 1-way analysis of variance with Bonferroni corrections for multiple comparisons. Trophoblast cells treated with both AM and 1% CSE demonstrated increased cellular invasion compared to NS controls (1.5-fold [P < .01] and 1.45-fold [P < .01], respectively). Cotreatment with the AM inhibitor significantly attenuated the increased invasion seen with both AM and CSE alone. Next, the placental tissue was obtained from 11 smokers and 11 nonsmokers at term and processed for immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (PCR) for AM. Placentas from smokers demonstrated more intense AM staining and increased AM gene (ADM) expression compared to placentas from nonsmokers (P = .004 for IHC, P = .022 for PCR). The CSE increases trophoblast cell invasion through an AM-mediated process, and placental AM expression is increased among term smokers compared to nonsmokers. These findings provide evidence that the AM pathway may play a role in the protection from preeclampsia seen in smokers. PMID:23653390

  13. Placental calcium pump: clinical-based evidence.

    PubMed

    Kasznica, John M; Petcu, Eugen B

    2003-01-01

    Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death. In this study we describe for the first time a case of placental calcification in a living fetus. The fetus of a normal 21-year-old pregnant woman showed heart abnormalities but the genetic analysis showed a normal male karyotype. The histology of the placenta demonstrated multiple intravillous linear and granular calcific incrustations The hemtoxylin/eosin stain of the sections revealed basement membrane calcific incrustations and intravillous calcium deposits. We postulate that the fetal circulation in the villi was impaired and the calcium that reached the villi from the mother was deposited at this level.

  14. Neurotrophins: Role in Placental Growth and Development.

    PubMed

    Sahay, A S; Sundrani, D P; Joshi, S R

    2017-01-01

    Neurotrophins, a family of closely related proteins, were originally identified as growth factors for survival, development, and function of neurons in both the central and peripheral nervous systems. Subsequently, neurotrophins have been shown to have functions in immune and reproductive systems. Neurotrophins like nerve growth factor and brain-derived neurotrophic factor (BDNF) are known to play an important role during pregnancy in the process of placental angiogenesis and maturation. Several studies have demonstrated the presence of neurotrophins in the human placenta. The current chapter reviews studies demonstrating the role of neurotrophins during pregnancy particularly in placental development. This chapter also focuses on the regional changes in neurotrophins in the human placenta and its interactions with other growth factors. Future research is needed to understand the mechanisms through which neurotrophins influence the growth and development of the placenta and pregnancy outcome.

  15. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.

    PubMed

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Chronic Placental Inflammation in Twin Pregnancies

    PubMed Central

    Bang, Heejin; Bae, Go Eun; Park, Ha Young; Kim, Yeon Mee; Choi, Suk-Joo; Oh, Soo-young; Roh, Cheong-Rae; Kim, Jung-Sun

    2015-01-01

    Background: Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies. Methods: Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed. Results: Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29–32 weeks) than in singleton placentas (33–36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p=.052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p<.05). Conclusions: The higher frequency of non-basal VUE in twin placentas and of CCA in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti-fetal rejection related to increased fetal antigens in twin pregnancies. The peak of CCA at an earlier gestational age in twin placentas than in singleton placentas suggests that CCA is influenced by placental maturation. PMID:26459409

  17. Placentation in mammals once grouped as insectivores.

    PubMed

    Carter, Anthony M; Enders, Allen C

    2010-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three subfamilies of tenrec have been examined. The interhemal region is cellular hemomonochorial in Echinops and Microgale but endotheliochorial in Micropotamogale. Golden moles, which are placed in the same order, have hemodichorial placentation. Many insectivores have complex arrangements for histotrophic nutrition involving columnar trophoblast cells. These range from areolae in moles through complexly folded hemophagous regions in tenrecs to the trophoblastic annulus in shrews. Of these placental characters, few offer support to current phylogenies. However, the case for placing hedgehogs and gymnures in a separate order (Erinaceomorpha) is bolstered by the presence of interstitial implantation, amniogenesis by cavitation, a hemochorial barrier and a prominent spongy zone; these features do not occur in shrews, moles or solenodons (Soricomorpha). Three insectivoran grade mammals deserve close attention as they have been selected for genome sequencing. One of these, the European hedgehog (Erinaceus europaeus), has not been studied with current methodology and renewed investigation of this or the closely related genus Atelerix should be a priority.

  18. The placental mammal ancestor and the post-K-Pg radiation of placentals.

    PubMed

    O'Leary, Maureen A; Bloch, Jonathan I; Flynn, John J; Gaudin, Timothy J; Giallombardo, Andres; Giannini, Norberto P; Goldberg, Suzann L; Kraatz, Brian P; Luo, Zhe-Xi; Meng, Jin; Ni, Xijun; Novacek, Michael J; Perini, Fernando A; Randall, Zachary S; Rougier, Guillermo W; Sargis, Eric J; Silcox, Mary T; Simmons, Nancy B; Spaulding, Michelle; Velazco, Paúl M; Weksler, Marcelo; Wible, John R; Cirranello, Andrea L

    2013-02-08

    To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.

  19. Topological Analysis of Placental Arteries:. Correlation with Neonatal Growth

    NASA Astrophysics Data System (ADS)

    Yamada, H.; Yakubo, K.

    2007-07-01

    The aim of study was to assess whether any network index of placental surface arteries was associated with neonatal birth weight. Twenty-six placentas were randomly selected between 34 and 41 weeks of gestational ages. Placental weights ranged 385 to 770 g; and neonatal weights ranged 1960 to 3680 g. After visualization of placental surface arteries by a milk injection method, network indices including the number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were determined. These network indices and placental weights were compared with neonatal birth weights. The Number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were found to be as follows (Mean ± SD); 84.7 ± 29.3, 0.0262 ± 0.0088, 15.8 ± 2.77, 7.83 ± 1.13, 0.0263 ± 0.0091, respectively. We found that neonatal birth weights correlate with the number of nodes of placental surface arteries (correlation coefficient R=0.40) and placental weights (R=0.52) both. However, the number of nodes of placental surface arteries was not associated with the placental weights or the gestational age. We for the first time found that a topological factor, i.e., the number of nodes of placental surface arteries correlated with neonatal growth. There was no correlation between numbers of nodes and placental weights. This suggests that the number of nodes affects fetal growth independent of placental weights. A topological factor of placental vasculization might significantly affect fetal growth in utero and determine risks of vascular diseases in their future lives.

  20. Placental p,p'-dichlorodiphenyldichloroethylene and cord blood immune markers.

    PubMed

    Brooks, Kevin; Hasan, Hanem; Samineni, Sridhar; Gangur, Venu; Karmaus, Wilfried

    2007-11-01

    Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.

  1. Placental Protein 13 (PP13) – A Placental Immunoregulatory Galectin Protecting Pregnancy

    PubMed Central

    Than, Nándor Gábor; Balogh, Andrea; Romero, Roberto; Kárpáti, Éva; Erez, Offer; Szilágyi, András; Kovalszky, Ilona; Sammar, Marei; Gizurarson, Sveinbjorn; Matkó, János; Závodszky, Péter; Papp, Zoltán; Meiri, Hamutal

    2014-01-01

    Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure

  2. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    PubMed

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  3. Placental programming of blood pressure in Indian children

    PubMed Central

    Winder, Nicola R; Krishnaveni, Ghattu V; Hill, Jacqueline C; Karat, Chitra LS; Fall, Caroline HD; Veena, Sargoor R; Barker, David JP

    2011-01-01

    Aim To determine whether the size and shape of the placental surface predict blood pressure in childhood. Methods We studied blood pressure in 471 nine-year-old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study. Results In the daughters of short mothers (placental breadth increased (β = 0.69 mmHg/cm, p = 0.05) and as the ratio of placental surface area to birthweight increased (p = 0.0003). In the daughters of tall mothers, SBP rose as the difference between placental length and breadth increased (β = 1.40 mmHg/cm, p = 0.007), that is as the surface became more oval. Among boys, associations with placental size were only statistically significant after adjusting for current BMI and height. After adjustment, SBP rose as placental breadth, area and weight decreased (for breadth β = −0.68 mmHg/cm, p < 0.05 for all three measurements). Conclusions The size and shape of the placental surface predict childhood blood pressure. Blood pressure may be programmed by variation in the normal processes of placentation: these include implantation, expansion of the chorionic surface in mid-gestation and compensatory expansion of the chorionic surface in late gestation. PMID:21166711

  4. [Placental 3D Doppler angiography: current and upcoming applications].

    PubMed

    Duan, J; Perdriolle-Galet, E; Chabot-Lecoanet, A-C; Callec, R; Beaumont, M; Chavatte-Palmer, P; Tsatsaris, V; Morel, O

    2015-02-01

    The placental dysfunction, which seems to be caused by a defect of trophoblastic invasion and impaired uterine vascular remodeling since the first trimester, is responsible in a non-exclusive way for the chronic placental hypoxia, resulting secondarily in the intra-uterine growth restriction (IUGR) and/or pre-eclampsia (PE). The quality of utero-placental vasculature is essential for a proper fetal development and a successful progress of pregnancy. However, the in vivo assessment of placental vascularization with non-invasive methods is complicated by the small size of placental terminal vessel and its complex architecture. Moreover, imaging with contrast agent is not recommended to pregnant women. Until recently, the fetal and maternal vascularization could only be evaluated through pulse Doppler of uterine arteries during pregnancy, which has little clinical value for utero-placental vascularization defects assessment. Recently, a non-invasive study, without use of contrast agent for vasculature evaluation of an organ of interest has become possible by the development of 3D Doppler angiography technique. The objective of this review was to make an inventory of its current and future applications for utero-placental vasculature quantification. The main findings of the literature on the assessment of utero-placental vascularization in physiological situation and major placental vascular dysfunction pathologies such as PE and IUGR were widely discussed.

  5. Cesarean Delivery for a Life-threatening Preterm Placental Abruption

    PubMed Central

    Okafor, II; Ugwu, EO

    2015-01-01

    Placental abruption is one of the major life-threatening obstetric conditions. The fetomaternal outcome of a severe placental abruption depends largely on prompt maternal resuscitation and delivery. A case of severe preterm placental abruption with intrauterine fetal death. Following a failed induction of labor with a deteriorating maternal condition despite resuscitation, emergency cesarean delivery was offered with good maternal outcome. Cesarean delivery could avert further disease progression and possible maternal death in cases of severe preterm placental abruption where vaginal delivery is not imminent. However, further studies are necessary before this could be recommended for routine clinical practice. PMID:27057388

  6. Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

    PubMed

    Gelber, Shari E; Brent, Elyssa; Redecha, Patricia; Perino, Giorgio; Tomlinson, Stephen; Davisson, Robin L; Salmon, Jane E

    2015-08-01

    Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

  7. Placental Imaging: Normal Appearance with Review of Pathologic Findings.

    PubMed

    Fadl, Shaimaa; Moshiri, Mariam; Fligner, Corinne L; Katz, Douglas S; Dighe, Manjiri

    2017-01-01

    The placenta plays a crucial role throughout pregnancy, and its importance may be overlooked during routine antenatal imaging evaluation. Detailed systematic assessment of the placenta at ultrasonography (US), the standard imaging examination during pregnancy, is important. Familiarity with the normal and abnormal imaging appearance of the placenta along with the multimodality and methodical approach for evaluation of its related abnormalities is necessary, so that radiologists can alert clinicians regarding appropriate prompt management decisions. This will potentially decrease fetal and maternal morbidity and mortality. This article reviews early placental formation and the expected imaging appearance of the placenta during pregnancy, as well as variations in its morphology. It also discusses various placental diseases and their potential clinical consequences. Placental pathologic conditions include abnormalities of placental size, cord insertion, placental and cord location, and placental adherence. Other conditions such as bleeding in and around the placenta, as well as trophoblastic and nontrophoblastic tumors of the placenta, are also discussed. US with Doppler imaging is the initial imaging modality of choice for placental evaluation. Magnetic resonance (MR) imaging is reserved for equivocal cases or when additional information is needed. Computed tomography (CT) has a limited role in evaluation of placental abnormalities because of the ionizing radiation exposure and the relatively limited assessment of the placenta; however, CT can provide important information in specific circumstances, particularly evaluation of trauma and staging of choriocarcinoma. This article also addresses recent techniques and updates in placental imaging, including elastography, diffusion-weighted MR imaging, and blood oxygen level-dependent (BOLD) MR imaging. These advanced imaging techniques may provide additional information in evaluation of abnormal placental adherence and

  8. Placental alkaline phosphatase (PLAP) study in diabetic human placental villi infected with Trypanosoma cruzi.

    PubMed

    Mezzano, L; Sartori, M J; Lin, S; Repossi, G; de Fabro, S P

    2005-01-01

    Previous work has demonstrated that PLAP activity decreases in serum and placental villi from term chagasic and diabetic pregnant women. In vitro, T. cruzi induces changes in human syncytiotrophoblast's PLAP. Our aim was to determine if infection with T. cruzi induces changes in PLAP activity in diabetic and chagasic women's placenta, in order to elucidate if PLAP plays a role in the mechanisms of interaction between placenta and T. cruzi, and whether hyperglycemic conditions could worsen the placental infection. Using zymogrammes, Western blot, biochemical and immunohistological techniques, PLAP activity was determined in placental villi from diabetic and chagasic women, and in normal placentas cultured under hyperglycemic conditions with or without trypomastigotes. A significant reduction of PLAP expression was immunologically detected in infected diabetic and normal placental villi cultured under hyperglycemic conditions of 71 and 81%, respectively, compared with controls. A significant decrease of PLAP specific activity was registered in homogenates and in the culture media from both infected diabetic and normal placentas under hyperglycemic conditions (of about 50-70%), and in chagasic ones (of about 87%), when compared with controls. Thus, PLAP might be involved in parasite invasion and diabetic and hyperglycemic placentas could be more susceptible to T. cruzi infection.

  9. Role of placental alkaline phosphatase in the interaction between human placental trophoblast and Trypanosoma cruzi.

    PubMed

    Sartori, M J; Lin, S; Frank, F M; Malchiodi, E L; de Fabro, S P

    2002-02-01

    Congenital Chagas disease, due to the intracellular parasite Trypanosoma cruzi, is associated with premature labor, miscarriage, and placentitis. Human enzyme placental alkaline phosphatase (PLAP) (EC 3.1.3.1.) is membrane-anchored through glycosylphosphatidylinositol (GPI). PLAP is present in plasma in late pregnancy, 36 to 40 weeks; there are lower levels in maternal Chagas disease. Infants born to such mothers may have congenital Chagas disease. Human placental villi (PV) were treated with phospholipase-C (PL-C) and then cultured with T. cruzi to determine the effect of the parasites on PLAP activity as an in vitro model. There is less PLAP activity after treatment by PL-C and during culture with T. cruzi. Pretreatment of PV with PL-C before culture with T. cruzi yielded essentially normal specific activity of PLAP and prevented or greatly reduced infective penetration of villi by parasites. The results are consistent with a pathogenetic role for placental alkaline phosphatase in congenital Chagas disease. Receptor activation of membrane attachment to PLAP may be a device used by T. cruzi to enable parasite invasion of human trophoblast. Copyright 2002 Elsevier Science.

  10. Increased placental trophoblast inclusions in placenta accreta.

    PubMed

    Adler, E; Madankumar, R; Rosner, M; Reznik, S E

    2014-12-01

    Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs. Published by Elsevier Ltd.

  11. Foetal placental blood flow in the lamb

    PubMed Central

    Faber, J. Job; Green, Thomas J.

    1972-01-01

    1. Fifteen sheep foetuses of 1·5-5·2 kg body weight were prepared with indwelling arterial and venous catheters for experimentation one to six days later. 2. Unanaesthetized foetuses were found to have mean arterial and central venous blood pressures of 40 ± 1·5 (S.E. of mean) and 2·0 ± 0·3 (S.E. of mean) mm Hg respectively, compared to intra-uterine pressure. Intra-uterine pressure was 16 ± 0·8 (S.E. of mean) mm Hg with respect to atmospheric pressure at mid-uterine level. 3. Mean placental blood flow of the foetuses was 199 ± 20 (S.E. of mean) ml./(min.kg body wt.). Mean cardiac output in eleven of the foetuses was 658 ± 102 (S.E. of mean) ml./(min.kg). 4. Mean foetal and maternal colloid osmotic pressures were 17·5 ± 0·7 (S.E. of mean) and 20·5 ± 0·6 (S.E. of mean) mm Hg respectively at 38° C. 5. Intravenous infusions into six ewes of 1·8 mole of mannitol and 0·4 mole of NaCl resulted in significant increases in foetal plasma osmolarity, sodium, potassium, and haemoglobin concentrations, without detectable transfer of mannitol to the foetal circulation. 6. In the sheep placenta there is osmotic and hydrostatic equilibration of water. As a consequence, there should be an interaction between foetal placental blood flow and foetal water exchange with the maternal circulation. It was concluded that this interaction tends to stabilize foetal placental blood flow. PMID:5039279

  12. Placental/umbilical cord blood transplantation.

    PubMed

    Sirchia, G; Rebulla, P

    1999-08-01

    In this article we summarize the clinical outcome of unrelated placental/umbilical cord blood (CB) transplantation, discuss the biological characteristics of CB hematopoietic progenitor/stem cells (HPC) and balance the relative advantages and disadvantages of this therapy as compared with transplantation of other HPC sources. Moreover, we discuss CB banking programs at local, national and international levels. The data reported by the investigators of the New York Placental/Umbilical Cord Blood Program and of the Eurocord group indicate that the clinical outcome of allogeneic unrelated CB transplantation is significantly related to cell dose, being more effective in children than in adults, and is highly dependent on disease stage at transplantation. Furthermore, both studies show lower graft-versus-host disease (GvHD) frequency and severity and prolonged time intervals for platelet engraftment as compared to those of bone marrow and mobilized peripheral blood recipients. Although the data from the New York Placental/Umbilical Cord Blood Program seem to support a negative effect of HLA differences, the latter were not significantly associated with survival in the Eurocord series. Additional observations are therefore necessary to collect conclusive evidence in this regard. Currently available data show that CB contains a higher proportion of primitive HPC and that CB-HPC possess higher proliferation and expansion potentials as compared to adult bone marrow. Furthermore, there is some evidence indicating that CB-HPC are more adequate than HPC from other sources for genetic manipulation and gene therapy. Despite the significant advances in the knowledge of the biology and in the clinical use of CB, a number of problems remain unsolved, including the standardization of banking procedures and unit quality and the development of suitable protocols for transplantation of adult patients.

  13. A novel pattern of placental leucine transfer during mid to late gestation in a highly placentotrophic viviparous lizard.

    PubMed

    Itonaga, Keisuke; Wapstra, Erik; Jones, Susan M

    2012-06-01

    Placentotrophy is the nourishment of embryos by resources provided via the placenta during gestation. The magnitude and timing of placental nutrient support during pregnancy are important for embryonic growth, especially in highly placentotrophic animals such as mammals. However, no study has yet investigated how placental organic nutrient support may change during pregnancy in highly placentotrophic viviparous reptiles. Amino acids are essential nutrients for embryonic growth and leucine is a common amino acid. The magnitude and timing of placental leucine transfer may affect embryonic growth and mass and, therefore, offspring phenotype. In this study, female Pseudemoia entrecasteauxii, a highly placentotrophic viviparous skink, were collected throughout gestation. We injected (3)H-leucine into these gravid females and assessed the transfer of (3)H-leucine into maternal compartments (i.e., the blood and the liver), and into embryonic compartments (i.e., the embryo, the yolk, and the amniotic fluid). At either 60 or 120 min post-injection, the radioactivity in each sample was extracted and then counted, and the transfer ratio was calculated. Our results provide direct evidence that circulating maternal leucine passes through the placenta into the embryos in this species. The relative rate of placental leucine transfer did not alter during mid to late gestation. This suggests the steady somatic growth of the embryos during mid-late pregnancy is dependent upon the placental transfer of nutrients rather than yolk stores. This pattern of placental nutrient support may determine offspring body size at birth and, therefore, offspring fitness in P. entrecasteauxii. © 2012 WILEY PERIODICALS, INC.

  14. The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis.

    PubMed

    Huang, Q T; Chen, J H; Zhong, M; Xu, Y Y; Cai, C X; Wei, S S; Hang, L L; Liu, Q; Yu, Y H

    2014-08-01

    Several epidemiological studies have found a positive association between chronic hepatitis B virus (CHB) infection and the risk of placental abruption and placenta previa, but various studies have reported conflicting findings. The objective was to systematically review the literature to determine a possible association between CHB infection and these two placental complications. We conducted a computerized search in electronic database through March 1, 2014, supplemented with a manual search of reference lists, to identify original published research on placental abruption and placenta previa rates in women with CHB infection. Data were independently extracted, and relative risks were calculated. The meta-analysis was performed using Stata version 10.0 software. Five studies involving 9088 placenta previa cases were identified. No significant association between CHB infection and placenta previa was identified (OR = 0.98, 95% CI = 0.60-1.62). Five studies involving 15571 placental abruption cases were identified. No significant association between CHB infection and placental abruption was identified (OR = 1.42, 95% CI, 0.93-2.15). The immune response against the virus represents a key factor in determining infection outcomes. No observation of significant increased risk of the placental complications could be partially explained by the complex immune response during CHB infection. Our meta-analysis found no evidence of significant associations between CHB infection and increased risk of placental abruption as well as placenta previa. Further well-designed studies were warranted to assess any potential association between CHB infection and increased risk of placental abruption as well as placenta previa. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Placental glucose dehydrogenase polymorphism in Koreans.

    PubMed

    Kim, Y J; Paik, S G; Park, H Y

    1994-12-01

    The genetic polymorphism of placental glucose dehydrogenase (GDH) was investigated in 300 Korean placentae using horizontal starch gel electrophoresis. The allele frequencies for GDH1, GDH2 and GDH3 were 0.537, 0.440 and 0.005, respectively, which were similar to those in Japanese. We also observed an anodal allele which was similar to the GDH4 originally reported in Chinese populations at a low frequency of 0.015. An additional new cathodal allele (named GDH6) was observed in the present study with a very low frequency of 0.003.

  16. Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

    PubMed

    Parra-Saavedra, M; Crovetto, F; Triunfo, S; Savchev, S; Peguero, A; Nadal, A; Parra, G; Gratacos, E; Figueras, F

    2013-12-01

    To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Providing a Placental Transfusion in Newborns Who Need Resuscitation

    PubMed Central

    Katheria, Anup C.; Brown, Melissa K.; Rich, Wade; Arnell, Kathy

    2017-01-01

    Over the past decade, there have been several studies and reviews on the importance of providing a placental transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. However, premature and term newborns who require resuscitation have impaired transitional hemodynamics and may warrant different methods to actively provide a placental transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a placental transfusion in these circumstances and methods for implementation. Several factors including cord clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion is beneficial, it is not always straightforward to implement and can be performed using different methods, making this basic procedure important to discuss. We will review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:28180126

  18. Developmental modularity and the marsupial-placental dichotomy.

    PubMed

    Goswami, A; Weisbecker, V; Sánchez-Villagra, M R

    2009-05-15

    The contrasting evolutionary histories of marsupial and placental mammals have often been attributed to their different reproductive strategies. The speciose placentals develop mainly in utero and have radiated into diverse niches, whereas marsupials are born in a highly altricial state with immediate functional requirements and are limited in taxonomic, ecological, and morphological diversity. These differences have been tied to heterochrony, and it has been hypothesized that coordinated shifts in developmental timing occur among functionally- or developmentally related structures, such as forelimbs in marsupials. We use new ossification sequence data for 11 marsupial and 14 placental species to assess the integration of first ossification timing among skeletal elements. Although cranial elements fail to demonstrate significant coordination, marsupials and placentals differ markedly in postcranial integration. Marsupials display independent anterior and posterior developmental modules, whereas placentals show significant integration of the entire appendicular skeleton. This developmental integration of the placental postcranium is consistent with a recent study of phenotypic modularity in limbs of placental mammals, showing a potential correspondence between integration of developmental timing and of shape. The observed differences in postcranial integration between marsupials and placentals may reflect the disparate evolutionary histories of these two mammalian clades.

  19. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.

    PubMed

    Prince, Amanda L; Ma, Jun; Kannan, Paranthaman S; Alvarez, Manuel; Gisslen, Tate; Harris, R Alan; Sweeney, Emma L; Knox, Christine L; Lambers, Donna S; Jobe, Alan H; Chougnet, Claire A; Kallapur, Suhas G; Aagaard, Kjersti M

    2016-05-01

    Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis

  20. Multimodality imaging of placental masses: a pictorial review.

    PubMed

    Jha, Priyanka; Paroder, Viktoriya; Mar, Winnie; Horowtiz, Jeanne M; Poder, Liina

    2016-12-01

    Placental masses are uncommonly identified at the time of obstetric ultrasound evaluation. Understanding the pathologies presenting as placental masses is key for providing a differential diagnosis and guiding subsequent management, which may include additional imaging with magnetic resonance (MR) imaging. Potential benign entities include chorioangiomas and teratomas. Larger chorioangiomas can cause fetal cardiovascular issues from volume overload. Placental mesenchymal dysplasia has an association with fetal anomalies and detailed fetal evaluation should be performed when it is suspected. Identifying other cystic masses such as partial and complete moles is crucial to prevent erroneous pregnancy termination. This review addresses normal imaging appearance of the placenta on ultrasound and MR imaging and describes various trophoblastic and nontrophoblastic placental masses. Potential placental mass mimics including uterine contractions and thrombo-hematomas are also presented.

  1. Ethical aspects of banking placental blood for transplantation.

    PubMed

    Sugarman, J; Reisner, E G; Kurtzberg, J

    1995-12-13

    Transplantation of blood cells harvested from the umbilical cord immediately after birth has been effective in repopulating the bone marrow. These placental blood transplantations may be safer than conventional bone marrow transplantations and may suspend the need to harvest bone marrow, a process fraught with difficulties. Further understanding and advancement of this emerging technology require developing large banks of placental blood. In this article, we examine some of the ethical issues associated with placental blood banking, including (1) questions about ownership of the tissue, (2) the necessity and nature of obtaining informed consent from parents for harvesting placental blood and the information-gathering process associated with it, (3) obligations to notify parents and children of the results of medical testing for infectious diseases and genetic information, (4) matters of privacy and confidentiality related to such information, and (5) the need for fair and equitable harvesting of and access to placental blood.

  2. Exercise in pregnancy: an association with placental weight?

    PubMed

    Hilde, Gunvor; Eskild, Anne; Owe, Katrine Mari; Bø, Kari; Bjelland, Elisabeth K

    2017-02-01

    Women with high levels of physical exercise have an increased demand for oxygen and nutrients. Thus, in pregnancies of women with high levels of exercise, it is conceivable that the supply of oxygen and nutrients to the placenta is suboptimal, and growth could be impaired. The objective was to study the association of frequency of exercise during pregnancy with placental weight and placental to birthweight ratio. This was a prospective study of 80,515 singleton pregnancies in the Norwegian Mother and Child Cohort Study. Frequency of exercise was self-reported by a questionnaire at pregnancy weeks 17 and 30. Information on placental weight and birthweight was obtained by linkage to the Medical Birth Registry of Norway. Placental weight decreased with increasing frequency of exercise (tests for trend, P < .001). For nonexercisers in pregnancy week 17, the crude mean placental weight was 686.1 g compared with 667.3 g in women exercising ≥6 times weekly (difference, 18.8 g; 95% confidence interval, 12.0-25.5). Likewise, in nonexercisers in pregnancy week 30, crude mean placental weight was 684.9 g compared with 661.6 g in women exercising ≥6 times weekly (difference, 23.3 g; 95% confidence interval, 14.9-31.6). The largest difference in crude mean placental weight was seen between nonexercisers at both time points and women exercising ≥6 times weekly at both time points (difference, 31.7 g; 95% confidence interval, 19.2-44.2). Frequency of exercise was not associated with placental to birthweight ratio. We found decreasing placental weight with increasing frequency of exercise in pregnancy. The difference in placental weight between nonexercisers and women with exercising ≥6 times weekly was small and may have no clinical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Discriminative Learning for Automatic Staging of Placental Maturity via Multi-layer Fisher Vector

    NASA Astrophysics Data System (ADS)

    Lei, Baiying; Yao, Yuan; Chen, Siping; Li, Shengli; Li, Wanjun; Ni, Dong; Wang, Tianfu

    2015-07-01

    Currently, placental maturity is performed using subjective evaluation, which can be unreliable as it is highly dependent on the observations and experiences of clinicians. To address this problem, this paper proposes a method to automatically stage placenta maturity from B-mode ultrasound (US) images based on dense sampling and novel feature descriptors. Specifically, our proposed method first densely extracts features with a regular grid based on dense sampling instead of a few unreliable interest points. Followed by, these features are clustered using generative Gaussian mixture model (GMM) to obtain high order statistics of the features. The clustering representatives (i.e., cluster means) are encoded by Fisher vector (FV) for staging accuracy enhancement. Differing from the previous studies, a multi-layer FV is investigated to exploit the spatial information rather than the single layer FV. Experimental results show that the proposed method with the dense FV has achieved an area under the receiver of characteristics (AUC) of 96.77%, sensitivity and specificity of 98.04% and 93.75% for the placental maturity staging, respectively. Our experimental results also demonstrate that the dense feature outperforms the traditional sparse feature for placental maturity staging.

  4. Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues.

    PubMed

    Ma, K; Lian, Y; Zhou, S; Hu, R; Xiong, Y; Ting, P; Xiong, Y; Li, X; Wang, X

    2014-01-01

    To detect the candidate genes for preeclampsia (PE). The gene expression profiles in preeclamptic and normal placental tissues were analyzed using cDNA microarray approach and the altered expression of important genes were further confirmed by real-time RT-PCR (reverse transcription polymerase chain reaction) technique. Total RNA was extracted from placental tissues of three cases with severe PE and from three cases with normal pregnancy. After scanning, differentially expressed genes were detected by software. In two experiments (the fluorescent labels were exchanged), a total of 111 differentially expressed genes were detected. In placental tissue ofpreeclamptic pregnancy, 68 differentially expressed genes were up-regulated, and 44 differentially expressed genes were down-regulated. Of these genes, 16 highly differentially expressed genes were confirmed by real-time fluorescent quantitative RT-PCR, and the result showed that the ratio of gene expression differences was comparable to that detected by cDNA microarray. The results of bioinformatic analysis showed that encoding products of differentially expressed genes were correlated to infiltration of placenta trophoblastic cells, immunomodulatory factors, pregnancy-associated plasma protein, signal transduction pathway, and cell adhesion. Further studies on the biological function and regulating mechanism of these genes will provide new clues for better understanding of etiology and pathogenesis of PE.

  5. Immunohistochemical Expression of Myeloperoxidase in Placental Samples of Systematic Lupus Erythematosus Pregnancies

    PubMed Central

    Heidari, Zahra; Mahmoudzadeh Sagheb, Hamidreza; Sheibak, Nadia

    2016-01-01

    Objective: Reports of increased level of Myeloperoxidase (MPO) in plasma and placental extracts of Systematic Lupus Erythematosus (SLE) has been proposed that MPO may have an important role in this pregnancy complication. In present study immunohistochemical MPO expression was investigated in placental samples of SLE women compared with normal controls. Materials and methods: Ten patients with SLE were recruited as case group. Control group was selected from mothers with normal uncomplicated pregnancies. A monoclonal antibody specific for MPO was used for immunohistochemical staining and then the staining was quantified and differences between groups were compared using Mann-Whitney U test. Results: There were significant differences in the expression levels of MPO in the syncytiotrophoblast cells and the extravillous trophoblast cells between the control and SLE groups (p < 0.05). There were no significant differences in the expression level of MPO in the vascular endothelium and the relative number of the MPO-positive leukocytes in placental tissue between SLE and control groups (p > 0.05). Conclusion: The present study showed that MPO expression is increased in syncytiotrophoblast cells and the extravillous trophoblast cells of SLE placentas compared to healthy subjects. It seems that these changes are able to impress structure and function of placenta and survival of the fetus. PMID:27648095

  6. Transport of nanoparticles through the placental barrier.

    PubMed

    Kulvietis, Vytautas; Zalgeviciene, Violeta; Didziapetriene, Janina; Rotomskis, Ricardas

    2011-12-01

    Nanoparticles (NP) are organic or inorganic substances, the size of which ranges from 1 to 100 nm, and they possess specific properties which are different from those of the bulk materials in the macroscopic scale. In a recent decade, NP were widely applied in biomedicine as potential probes for imaging, drug-delivery systems and regenerative medicine. However, rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of NP on human health and environment. In the present review, special attention is paid to the fetal exposure to NP during the period of pregnancy. The ability to control the beneficial effects of NP and to avoid toxicity during treatment requires comprehensive knowledge about the distribution of NP in maternal body and possible penetration through the maternal-fetal barrier that might impair the embryogenesis. The initial in vivo and ex vivo studies imply that NP are able to cross the placental barrier, but the passage to the fetus depends on the size and the surface coating of NP as well as on the experimental model. The toxicity assays indicate that NP might induce adverse physiological effects and impede embryogenesis. The molecular transport mechanisms which are responsible for the transport of nanomaterials across the placental barrier are still poorly understood, and there is a high need for further studies in order to resolve the NP distribution patterns in the organism and to control the beneficial effects of NP applications during pregnancy without impeding the embryogenesis.

  7. Protein Profiling of Preeclampsia Placental Tissues

    PubMed Central

    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y.

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia. PMID:25392996

  8. Protein profiling of preeclampsia placental tissues.

    PubMed

    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y; He, Jin; Ye, Fei

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

  9. Confined placental mosaicisms and uniparental disomy

    SciTech Connect

    Kalousek, D.K.; Langlois, S.; Harrison, K.J.

    1994-09-01

    Approximately 2% of pregnancies studied with chorionic villous sampling (CVS) show confined placental mosaicism (CPM) which persists to term in 50-70% of cases. An increased frequency of complications, such as intrauterine fetal growth restriction or intrauterine death, is observed in these pregnancies. As trisomic zygote rescue is a common mechanism responsible for CPM, fetal uniparental disomy (UPD), resulting from the loss of the extra trisomic chromosome in the embryonic stem cells, would be expected to occur in a proportion of pregnancies with CPM. We have studied 27 pregnancies with CPM involving trisomies for chromosomes 2, 7, 9, 10, 12, and 16 for involvement of specific cell lineage(s) and levels of mosaicism in term placentas. Also, DNA from the parents and infant was analyzed for UPD or biparental disomy (BPD). Five infants with UPD for chromosome 16 and one infant with UPD for chromosome 7 were detected. All other infants showed BPD for the chromosome involved in CPM. For trisomy 16 mosaic gestations, a close correlation between high levels of trisomic cells in placenta and intrauterine fetal growth restriction has been found irrespective of the type of disomy present in the infant. The effect of other trisomies (2, 7, 9, 10, 12) on placental function appears to be similar, but the low numbers of pregnancies studied and lack of detection of UPD for chromosomes 2, 9, 10 and 12 does not allow a definitive conclusion.

  10. The Role of Placental Tryptophan Catabolism

    PubMed Central

    Sedlmayr, Peter; Blaschitz, Astrid; Stocker, Roland

    2014-01-01

    This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence of metabolites of the kynurenine pathway mediate immunoregulation and exert antimicrobial functions. In addition to the decidual glandular epithelium, IDO1 is localized in the vascular endothelium of the villous chorion and also in the endothelium of spiral arteries of the decidua. Possible consequences of IDO1-mediated catabolism of Trp in the endothelium encompass antimicrobial activity and immunosuppression, as well as relaxation of the placental vasotonus, thereby contributing to placental perfusion and growth of both placenta and fetus. It remains to be evaluated whether other enzymes mediating Trp oxidation, such as indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of relevance to the biology of the placenta. PMID:24904580

  11. Placental transcriptome co-expression analysis reveals conserved regulatory program across gestation

    USDA-ARS?s Scientific Manuscript database

    Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organization of the placental transcriptome through a systematic a...

  12. IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics.

    PubMed

    Bianco-Miotto, T; Blundell, C; Buckberry, S; Chamley, L; Chong, S; Cottrell, E; Dawson, P; Hanna, C; Holland, O; Lewis, R M; Moritz, K; Myatt, L; Perkins, A V; Powell, T; Saffery, R; Sferruzzi-Perri, A; Sibley, C; Simmons, D; O'Tierney-Ginn, P F

    2016-12-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.

  13. Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

    PubMed Central

    Meng, Wenbin; Shang, Hongkai; Li, Shaofu; Sloboda, Deborah M.; Ehrlich, Loreen; Lange, Karolin; Xu, Huaisheng; Henrich, Wolfgang; Dudenhausen, Joachim W.; Plagemann, Andreas; Newnham, John P.; Challis, John R. G.

    2015-01-01

    Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved. PMID:25063551

  14. Placental corticotrophin-releasing hormone, local effects and fetomaternal endocrinology.

    PubMed

    King, B R; Nicholson, R C; Smith, R

    2001-12-01

    The human placenta produces corticotrophin-releasing hormone (CRH) in exponentially increasing amounts during pregnancy with peak levels during labour. CRH in human pregnancy appears to be involved in many aspects of pregnancy including placental bloodflow, placental prostaglandin production, myornetrial function, fetal pituitary and adrenal function and the maternal stress axis. Since fetal cortisol levels are associated with pulmonary development and maturity, placental CRH may have an indirect role in fetal development.Although the precise role of placental CRH in the regulation of gestational length and timing of parturition is unclear it appears to be involved in a placental clock. While glucocorticoids inhibit hypothalamic CRH production they stimulate CRH gene expression in the placenta.This difference may allow the fetal and maternal stress axes to influence this placental clock.Maternal CRH levels are elevated in many pathological conditions of pregnancy where fetal well-being is compromised, and in these situations it may act to maintain a stable intrauterine environment. Therefore, CRH appears to link placental function, maternal well-being, fetal well-being and fetal development to the duration of gestation and the timing of parturition.

  15. Placental exosomes in normal and complicated pregnancy.

    PubMed

    Mitchell, Murray D; Peiris, Hassendrini N; Kobayashi, Miharu; Koh, Yong Q; Duncombe, Gregory; Illanes, Sebastian E; Rice, Gregory E; Salomon, Carlos

    2015-10-01

    While there is considerable contemporary interest in elucidating the role of placenta-derived extracellular vesicles in normal and complicated pregnancies and their utility as biomarkers and therapeutic interventions, progress in the field is hindered by a lack of standardized extracellular vesicle taxonomy and isolation protocols. The term "extracellular vesicle" is nonspecific and refers to all membrane-bound vesicles from nanometer to micrometer diameters and of different biogenic origins. To meaningfully ascribe biological function and/or diagnostic and therapeutic utility to extracellular vesicles, and in particular exosomes, greater specificity and vesicle characterization is required. The current literature relating to exosome biology must be interpreted in this context. Exosomes are a subtype of extracellular vesicle that are specifically defined by an endosomal biogenesis and particle size (40-120 nm) and density (1.13-1.19 g/mL(-1)). Exosomes are specifically package with signaling molecules (including protein, messenger RNA, microRNA, and noncoding RNA) and are released by exocytosis into biofluid compartments. Exosomes regulate the activity of both proximal and distal target cells, including translational activity, angiogenesis, proliferation, metabolism, and apoptosis. As such, exosomal signaling represents an integral pathway mediating intercellular communication. During pregnancy, the placenta releases exosomes into the maternal circulation from as early as 6 weeks of gestation. Release is regulated by factors that include both oxygen tension and glucose concentration and correlates with placental mass and perfusion. The concentration of placenta-derived exosomes in maternal plasma increases progressively during gestation. Exosomes isolated from maternal plasma are bioactive in vitro and are incorporated into target cells by endocytosis. While the functional significance of placental exosomes in pregnancy remains to be fully elucidated, available

  16. Developmental programming: impact of testosterone on placental differentiation

    PubMed Central

    Beckett, EM; Astapova, O; Steckler, TL; Veiga-Lopez, A; Padmanabhan, V

    2014-01-01

    Gestational testosterone (T) treatment causes maternal hyperinsulinemia, intra-uterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is likely the cause of fetal growth retardation in gestational T-treated sheep. This study tested if T excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational T (aromatizable androgen) against dihydrotestosterone (DHT; non-aromatizable androgen) or T plus androgen antagonist, flutamide, was used to determine whether the effects of T in placental differentiation were programmed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational T on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that 1) gestational T treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, 2) placental advancement is facilitated at least in part by androgenic actions of T and is not a function of disrupted insulin homeostasis, and 3) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low birth weight female offspring. Findings from this study may be of relevance to women with PCOS, whose reproductive and metabolic phenotype is captured by the gestational T-treated offspring. PMID:24840528

  17. Risk of placental abruption in relation to migraines and headaches.

    PubMed

    Sanchez, Sixto E; Williams, Michelle A; Pacora, Percy N; Ananth, Cande V; Qiu, Chungfang; Aurora, Sheena K; Sorensen, Tanya K

    2010-10-26

    Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders. Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20). A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75). The odds of placental abruption was 2.11 (95% CI 1.00-4.45) for migraineurs without aura; and 1.59 (95% 0.70-3.62) for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57). This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

  18. Maternal obesity and sex-specific differences in placental pathology.

    PubMed

    Leon-Garcia, Sandra M; Roeder, Hilary A; Nelson, Katharine K; Liao, Xiaoyan; Pizzo, Donald P; Laurent, Louise C; Parast, Mana M; LaCoursiere, D Yvette

    2016-02-01

    Adverse effects of obesity have been linked to inflammation in various tissues, but studies on placental inflammation and obesity have demonstrated conflicting findings. We sought to investigate the influence of pregravid obesity and fetal sex on placental histopathology while controlling for diabetes and hypertension. Placental histopathology focusing on inflammatory markers of a cohort of normal weight (BMI = 20-24.9) and obese (BMI ≥ 30) patients was characterized. Demographic, obstetric and neonatal variables were assessed. 192 normal and 231 obese women were included. Placental characteristics associated with obesity and fetal sex independent of diabetes and hypertension were placental disc weight >90(th) percentile, decreased placental efficiency, chronic villitis (CV), fetal thrombosis, and normoblastemia. Additionally, female fetuses of obese mothers had higher rates of CV and fetal thrombosis. Increasing BMI increased the risk of normoblastemia and CV. The final grade and extent of CV was significantly associated with obesity and BMI, but not fetal gender. Finally, CV was less common in large-for-gestation placentas. Maternal obesity results in placental overgrowth and fetal hypoxia as manifested by normoblastemia; it is also associated with an increased incidence of CV and fetal thrombosis, both more prevalent in female placentas. We have shown for the first time that the effect of maternal obesity on placental inflammation is independent of diabetes and hypertension, but significantly affected by fetal sex. Our data also point to the intriguing possibility that CV serves to normalize placental size, and potentially fetal growth, in the setting of maternal obesity. Copyright © 2015. Published by Elsevier Ltd.

  19. Developmental programing: impact of testosterone on placental differentiation.

    PubMed

    Beckett, E M; Astapova, O; Steckler, T L; Veiga-Lopez, A; Padmanabhan, V

    2014-08-01

    Gestational testosterone treatment causes maternal hyperinsulinemia, intrauterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring.

  20. Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency.

    PubMed

    Williams, Carmen J; Chu, Alison; Jefferson, Wendy N; Casero, David; Sudhakar, Deepthi; Khurana, Nevil; Hogue, Claire P; Aryasomayajula, Chinmayi; Patel, Priya; Sullivan, Peggy; Padilla-Banks, Elizabeth; Mohandessi, Shabnam; Janzen, Carla; Wadehra, Madhuri

    2017-03-14

    Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses. Placentas of Emp2(-/-) fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2(-/-) fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans and suggest it may be a new biomarker for placental insufficiency.

  1. EFFECT OF DMPS AND DMSA ON THE PLACENTAL AND FETAL DISPOSITION OF METHYLMERCURY

    PubMed Central

    Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

    2009-01-01

    Methylmercury (CH3Hg+) is a serious environmental toxicant. Exposure to this metal during pregnancy can cause serious neurological and developmental defects in a developing fetus. Surprisingly, little is known about the mechanisms by which mercuric ions are transported across the placenta. Although it has been shown that 2,3-dimercaptopropane-1-sulfonate (DMPS) and 2,3-dimercaptosuccinic acid (DMSA) are capable of extracting mercuric ions from various organs and cells, there is no evidence that they are able to extract mercury from placental or fetal tissues following maternal exposure to CH3Hg+. Therefore, the purpose of the current study was to evaluate the ability of DMPS and DMSA to extract mercuric ions from placental and fetal tissues following maternal exposure to CH3Hg+. Pregnant Wistar rats were exposed to CH3HgCl, containing [203Hg], on day 11 or day 17 of pregnancy and treated 24 h later with saline, DMPS or DMSA. Maternal organs, fetuses, and placentas were harvested 48 h after exposure to CH3HgCl. The disposition of mercuric ions in maternal organs and tissues was similar to that reported previously by our laboratory. The disposition of mercuric ions in placentas and fetuses appeared to be dependent upon the gestational age of the fetus. The fetal and placental burden of mercury increased as fetal age increased and was reduced by DMPS and DMSA, with DMPS being more effective. The disposition of mercury was examined in liver, total renal mass, and brain of fetuses harvested on gestational day 19. On a per gram tissue basis, the greatest amount of mercury was detected in the total renal mass of the fetus, followed by brain and liver. DMPS and DMSA reduced the burden of mercury in liver and brain while only DMPS was effective in the total renal mass. The results of the current study are the first to show that DMPS and DMSA are capable of extracting mercuric ions, not only from maternal tissues, but also from placental and fetal tissues following maternal

  2. Effect of DMPS and DMSA on the placental and fetal disposition of methylmercury.

    PubMed

    Bridges, C C; Joshee, L; Zalups, R K

    2009-09-01

    Methylmercury (CH3Hg+) is a serious environmental toxicant. Exposure to this metal during pregnancy can cause serious neurological and developmental defects in a developing fetus. Surprisingly, little is known about the mechanisms by which mercuric ions are transported across the placenta. Although it has been shown that 2,3-dimercaptopropane-1-sulfonate (DMPS) and 2,3-dimercaptosuccinic acid (DMSA) are capable of extracting mercuric ions from various organs and cells, there is no evidence that they are able to extract mercury from placental or fetal tissues following maternal exposure to CH3Hg+. Therefore, the purpose of the current study was to evaluate the ability of DMPS and DMSA to extract mercuric ions from placental and fetal tissues following maternal exposure to CH3Hg+. Pregnant Wistar rats were exposed to CH3HgCl, containing [203Hg], on day 11 or day 17 of pregnancy and treated 24 h later with saline, DMPS or DMSA. Maternal organs, fetuses, and placentas were harvested 48 h after exposure to CH3HgCl. The disposition of mercuric ions in maternal organs and tissues was similar to that reported previously by our laboratory. The disposition of mercuric ions in placentas and fetuses appeared to be dependent upon the gestational age of the fetus. The fetal and placental burden of mercury increased as fetal age increased and was reduced by DMPS and DMSA, with DMPS being more effective. The disposition of mercury was examined in liver, total renal mass, and brain of fetuses harvested on gestational day 19. On a per gram tissue basis, the greatest amount of mercury was detected in the total renal mass of the fetus, followed by brain and liver. DMPS and DMSA reduced the burden of mercury in liver and brain while only DMPS was effective in the total renal mass. The results of the current study are the first to show that DMPS and DMSA are capable of extracting mercuric ions, not only from maternal tissues, but also from placental and fetal tissues following maternal

  3. Placental copper transport in the brindled mouse

    SciTech Connect

    Garnica, A.; Bates, J.

    1986-03-01

    Pregnant brindled (brin) mice were injected at 16 or 19 days gestation with 2 doses of CuCl/sub 2/ 6 mcg/g/dose, separated by 12 h, and sacrificed 6 h after the second. The copper conc. in placenta (P) and kidneys (K) of uninjected (UI) brin mice were higher than in UI controls, while conc. in liver (L) and fetal carcass (F) were lower. After injection (I), placental copper conc. increased while the carcass conc. remained unchanged. Brin mouse is a model for the human inborn error of copper metabolism, Menkes syndrome, which is characterized by signs of copper deficiency. These data indicate that metabolism of copper in brin fetus is abnormal, but depressed fetal copper levels cannot be corrected by acute copper dosing because of the sequestration of copper in placenta.

  4. Why is placentation abnormal in preeclampsia?

    PubMed Central

    Fisher, Susan J.

    2015-01-01

    The causes of preeclampsia remain one of the great medical mysteries of our time. This syndrome is thought to occur in two stages with abnormal placentation leading to a maternal inflammatory response. Specific regions of the placenta have distinct pathological features. During normal pregnancy, cytotrophoblasts emigrate from the chorionic villi and invade the uterus, reaching the inner third of the myometrium. This unusual process is made even more exceptional by the fact that the placental cells are hemi-allogeneic, co-expressing maternal and paternal genomes. Within the uterine wall, cytotrophoblasts deeply invade the spiral arteries. Cytotrophoblasts migrate up these vessels and replace, in a retrograde fashion, the maternal endothelial lining. They also insert themselves amongst the smooth muscle cells that form the tunica media. As a result, the spiral arteries attain the physiological properties that are required to adequately perfuse the placenta. In comparison, invasion of the venous side of the uterine circulation is minimal, sufficient to enable venous return. In preeclampsia, cytotrophoblast invasion of the interstitial uterine compartment is frequently shallow, although not consistently so. In many locations, spiral artery invasion is incomplete. There are many fewer endovascular cytotrophoblasts and some vessels retain portions of their endothelial lining with relatively intact muscular coats while others are not modified. Work from our group showed that these defects mirror deficits in the differentiation program that enables cytotrophoblast invasion of the uterine wall. During normal pregnancy, invasion is accompanied by downregulation of epithelial-like molecules that are indicative of their ectodermal origin and upregulation of numerous receptors and ligands that are typically expressed by endothelial or vascular smooth muscle cells. For example, the expression of epithelial-cadherin, the cell-cell adhesion molecule that many ectodermal

  5. Placental C4d deposition is a feature of defective placentation: observations in cases of preeclampsia and miscarriage.

    PubMed

    Kim, Eun Na; Yoon, Bo Hyun; Lee, Joong Yeup; Hwang, Doyeong; Kim, Ki Chul; Lee, JoonHo; Shim, Jae-Yoon; Kim, Chong Jai

    2015-06-01

    Placental C4d deposition is frequent in preeclampsia, and shallow placentation is a characteristic of both preeclampsia and miscarriage. This study was conducted to determine the relationship among placental C4d, maternal human leukocyte antigen (HLA) antibodies, and placental pathology in preeclampsia and miscarriage cases. The patient population (N = 104) included those with (1) preterm preeclampsia with fetal growth restriction (PE-FGR; n = 21), (2) preterm preeclampsia (PE; n = 20), (3) spontaneous preterm delivery (sPTD; n = 39), and (4) miscarriage (n = 24). C4d immunohistochemistry was performed, and the presence of maternal plasma HLA antibodies was examined. C4d staining of the syncytiotrophoblast was more frequent in PE-FGR patients (76.2 %) than in PE (10.0 %; p < 0.001) and sPTD (2.6 %; p < 0.001) patients. Maternal HLA antibody-positive rate was not different among the study groups. There was a significant correlation between C4d immunoreactivity and placental pathology consistent with maternal vascular underperfusion (p < 0.001) but not with maternal HLA antibody status. In miscarriages, the positive rates of C4d, HLA class I, and HLA class II antibodies were 58.3, 25.0, and 12.5 %, respectively. There was no correlation between the presence of maternal HLA class I or II antibodies and placental C4d immunoreactivity. This study confirms frequent placental C4d deposition in preeclampsia with fetal growth restriction and miscarriage. The association between placental C4d deposition and pathological findings of maternal vascular underperfusion suggests that C4d staining of the syncytiotrophoblast is a consequence of defective placentation rather than of a specific maternal immune response against fetal HLA. The study also demonstrates the usefulness of C4d as a biomarker of placentas at risk.

  6. Placental insulin-like growth factor II (IGF-II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus).

    PubMed

    Rutherford, Julienne N; Eklund, Amy; Tardif, Suzette

    2009-12-01

    The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin-like growth factor-II (IGF-II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF-II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF-II was extracted from frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF-II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF-II concentration (P = 0.03), and IGF-II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF-II concentration (r = -0.75, P = 0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF-II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the

  7. Decreased activation of placental mTOR family members is associated with the induction of intrauterine growth restriction by secondhand smoke in the mouse.

    PubMed

    Mejia, Camilo; Lewis, Josh; Jordan, Clinton; Mejia, Juan; Ogden, Connor; Monson, Troy; Winden, Duane; Watson, Marc; Reynolds, Paul R; Arroyo, Juan A

    2017-02-01

    Cigarette smoke is known to be a risk for the development of intrauterine growth restriction (IUGR). Our objective was to assess the effects of secondhand smoke (SHS) during pregnancy and to what extent it regulates the activation of mTOR family members and murine trophoblast invasion. Mice were treated to SHS for 4 days. Placental and fetal weights were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of placental trophoblast invasion. Western blots were utilized to assess the activation of caspase 3, XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal (2.3-fold) weights (p < 0.05); (2) decreased trophoblast invasion; (3) significantly decreased active caspase 3 (1.3-fold; p < 0.02) and increased active XIAP (3.6-fold; p < 0.05) in the placenta; and (4) a significant decrease in the activation of placental mTOR (2.1-fold; p < 0.05), p70 (1.9-fold; p < 0.05) and 4EBP1 (1.3-fold; p < 0.05). Confirmatory in vitro experiments revealed decreased trophoblast invasion when SW71 cells were treated with 0.5 or 1.0 % cigarette smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR via decreased activation of the mTOR family of proteins in the placenta. Increased activation of the placental XIAP protein could be a survival mechanism for abnormal trophoblast cells during SHS exposure. Further, CSE reduced trophoblast invasion, suggesting a direct causative effect of smoke on susceptible trophoblast cells involved in IUGR progression. These results provide important insight into the physiological consequences of SHS exposure and smoke-mediated placental disease.

  8. Placental toxicity of cadmium in the rat: an ultrastructural study.

    PubMed

    Di Sant'Agnese, P A; Jensen, K D; Levin, A; Miller, R K

    1983-01-01

    Pregnant rats on day 18 of gestation were injected s.c. with 40 mumol/kg CdCl2 which caused fetal death and placental necrosis. The placental changes were studied by electron microscopy and indicate that there is a direct placental toxic effect of cadmium which appears targeted at the trophoblast and, in particular, trophoblast cell layer II. Findings in cell layer II which suggest a toxic effect were lysosomal vesiculation, 'buckshot' nuclear chromatin clumping, nucleolar changes and apparent mitochondrial calcification. Furthermore, the selectivity of the effect on cell layer II and the rapidity of the necrosis are also consistent with a toxic effect. Trophoblast cell layer II first undergoes necrosis, but is rapidly followed by the rest of the trophoblast. Many of the changes at this necrotic stage suggest a secondary ischaemic effect or a combined ischaemic and toxic effect. Therefore it appears that cadmium induces placental necrosis via a direct effect on the trophoblast, especially on layer II.

  9. The new framework for understanding placental mammal evolution.

    PubMed

    Asher, Robert J; Bennett, Nigel; Lehmann, Thomas

    2009-08-01

    An unprecedented level of confidence has recently crystallized around a new hypothesis of how living placental mammals share a pattern of common descent. The major groups are afrotheres (e.g., aardvarks, elephants), xenarthrans (e.g., anteaters, sloths), laurasiatheres (e.g., horses, shrews), and euarchontoglires (e.g., humans, rodents). Compared with previous hypotheses this tree is remarkably stable; however, some uncertainty persists about the location of the placental root, and (for example) the position of bats within laurasiatheres, of sea cows and aardvarks within afrotheres, and of dermopterans within euarchontoglires. A variety of names for sub-clades within the new placental mammal tree have been proposed, not all of which follow conventions regarding priority and stability. More importantly, the new phylogenetic framework enables the formulation of new hypotheses and testing thereof, for example regarding the possible developmental dichotomy that seems to distinguish members of the newly identified southern and northern radiations of living placental mammals.

  10. Molecular phylogenetics and the origins of placental mammals.

    PubMed

    Murphy, W J; Eizirik, E; Johnson, W E; Zhang, Y P; Ryder, O A; O'Brien, S J

    2001-02-01

    The precise hierarchy of ancient divergence events that led to the present assemblage of modern placental mammals has been an area of controversy among morphologists, palaeontologists and molecular evolutionists. Here we address the potential weaknesses of limited character and taxon sampling in a comprehensive molecular phylogenetic analysis of 64 species sampled across all extant orders of placental mammals. We examined sequence variation in 18 homologous gene segments (including nearly 10,000 base pairs) that were selected for maximal phylogenetic informativeness in resolving the hierarchy of early mammalian divergence. Phylogenetic analyses identify four primary superordinal clades: (I) Afrotheria (elephants, manatees, hyraxes, tenrecs, aardvark and elephant shrews); (II) Xenarthra (sloths, anteaters and armadillos); (III) Glires (rodents and lagomorphs), as a sister taxon to primates, flying lemurs and tree shrews; and (IV) the remaining orders of placental mammals (cetaceans, artiodactyls, perissodactyls, carnivores, pangolins, bats and core insectivores). Our results provide new insight into the pattern of the early placental mammal radiation.

  11. Placental Abruption Revealed by Hemoperitoneum: A Case Report

    PubMed Central

    Bertholdt, C.; Vincent-Rohfritsch, A.; Tsatsaris, V.; Goffinet, F.

    2016-01-01

    Background Hemoperitoneum is a life-threatening surgical emergency. Diagnosis of the cause is often difficult, in particular, during pregnancy when it may be either obstetric or nonobstetric. Case We report the case of a hemoperitoneum caused by the backflow of blood through a uterine tube, due to placental abruption. Conclusion Hemoperitoneum in pregnant women with no other signs can reveal placental abruption. The difficulty in identifying the cause may delay appropriate management. PMID:27994944

  12. [Fetal circulation in normal pregnancy and in placental insufficiency].

    PubMed

    Ivanov, B; Malinova, M

    2010-01-01

    The fetal circulation is different from the adult circulation. One of the quite common conditions that are challenging to the developing fetus is placental hypoxia. Regardless of its cause, placental vascular insufficiency is commonly assumed to be an important factor in the development of intrauterine growth retardation. Several mechanisms are involved in the fetal adaptation to the decompensation during hypoxemia. Doppler Ultrasound technologies can help to evaluate of the fetal wellbeing.

  13. Multiscale modelling of the feto–placental vasculature

    PubMed Central

    Clark, A. R.; Lin, M.; Tawhai, M.; Saghian, R.; James, J. L.

    2015-01-01

    The placenta provides all the nutrients required for the fetus through pregnancy. It develops dynamically, and, to avoid rejection of the fetus, there is no mixing of fetal and maternal blood; rather, the branched placental villi ‘bathe’ in blood supplied from the uterine arteries. Within the villi, the feto–placental vasculature also develops a complex branching structure in order to maximize exchange between the placental and maternal circulations. To understand the development of the placenta, we must translate functional information across spatial scales including the interaction between macro- and micro-scale haemodynamics and account for the effects of a dynamically and rapidly changing structure through the time course of pregnancy. Here, we present steps towards an anatomically based and multiscale approach to modelling the feto–placental circulation. We assess the effect of the location of cord insertion on feto–placental blood flow resistance and flow heterogeneity and show that, although cord insertion does not appear to directly influence feto–placental resistance, the heterogeneity of flow in the placenta is predicted to increase from a 19.4% coefficient of variation with central cord insertion to 23.3% when the cord is inserted 2 cm from the edge of the placenta. Model geometries with spheroidal and ellipsoidal shapes, but the same volume, showed no significant differences in flow resistance or heterogeneity, implying that normal asymmetry in shape does not affect placental efficiency. However, the size and number of small capillary vessels is predicted to have a large effect on feto–placental resistance and flow heterogeneity. Using this new model as an example, we highlight the importance of taking an integrated multi-disciplinary and multiscale approach to understand development of the placenta. PMID:25844150

  14. Multiscale modelling of the feto-placental vasculature.

    PubMed

    Clark, A R; Lin, M; Tawhai, M; Saghian, R; James, J L

    2015-04-06

    The placenta provides all the nutrients required for the fetus through pregnancy. It develops dynamically, and, to avoid rejection of the fetus, there is no mixing of fetal and maternal blood; rather, the branched placental villi 'bathe' in blood supplied from the uterine arteries. Within the villi, the feto-placental vasculature also develops a complex branching structure in order to maximize exchange between the placental and maternal circulations. To understand the development of the placenta, we must translate functional information across spatial scales including the interaction between macro- and micro-scale haemodynamics and account for the effects of a dynamically and rapidly changing structure through the time course of pregnancy. Here, we present steps towards an anatomically based and multiscale approach to modelling the feto-placental circulation. We assess the effect of the location of cord insertion on feto-placental blood flow resistance and flow heterogeneity and show that, although cord insertion does not appear to directly influence feto-placental resistance, the heterogeneity of flow in the placenta is predicted to increase from a 19.4% coefficient of variation with central cord insertion to 23.3% when the cord is inserted 2 cm from the edge of the placenta. Model geometries with spheroidal and ellipsoidal shapes, but the same volume, showed no significant differences in flow resistance or heterogeneity, implying that normal asymmetry in shape does not affect placental efficiency. However, the size and number of small capillary vessels is predicted to have a large effect on feto-placental resistance and flow heterogeneity. Using this new model as an example, we highlight the importance of taking an integrated multi-disciplinary and multiscale approach to understand development of the placenta.

  15. Placental steroid deficiency: association with arylsulfatase A deficiency.

    PubMed Central

    Vidgoff, J; Buxman, M M; Shapiro, L J; Dimond, R L; Wilson, T G; Hepburn, C A; Tabei, T; Heinrichs, W R

    1982-01-01

    A family with an obstetric history consistent with placental sulfatase deficiency has X-linked ichthyosis. Steroid sulfatase deficiency was confirmed in placenta, leukocytes, and cultured skin fibroblasts of affected males; arylsulfatase A diminution was also observed in these tissues of both affected males and 2 generations of related females. No symptoms of metachromatic leukodystrophy are present in any family members. In this family, placental sulfatase deficiency, and arylsulfatase A pseudodeficiency are nonallelic. PMID:6123259

  16. Patterns of ossification in southern versus northern placental mammals.

    PubMed

    Hautier, Lionel; Bennett, Nigel C; Viljoen, Hermien; Howard, Lauren; Milinkovitch, Michel C; Tzika, Athanasia C; Goswami, Anjali; Asher, Robert J

    2013-07-01

    Consensus on placental mammal phylogeny is fairly recent compared to that for vertebrates as a whole. A stable phylogenetic hypothesis enables investigation into the possibility that placental clades differ from one another in terms of their development. Here, we focus on the sequence of skeletal ossification as a possible source of developmental distinctiveness in "northern" (Laurasiatheria and Euarchontoglires) versus "southern" (Afrotheria and Xenarthra) placental clades. We contribute data on cranial and postcranial ossification events during growth in Afrotheria, including elephants, hyraxes, golden moles, tenrecs, sengis, and aardvarks. We use three different techniques to quantify sequence heterochrony: continuous method, sequence-ANOVA (analysis of variance) and event-paring/Parsimov. We show that afrotherians significantly differ from other placentals by an early ossification of the orbitosphenoid and caudal vertebrae. Our analysis also suggests that both southern placental groups show a greater degree of developmental variability; however, they rarely seem to vary in the same direction, especially regarding the shifts that differ statistically. The latter observation is inconsistent with the Atlantogenata hypothesis in which afrotherians are considered as the sister clade of xenarthrans. Interestingly, ancestral nodes for Laurasiatheria and Euarchontoglires show very similar trends and our results suggest that developmental homogeneity in some ossification sequences may be restricted to northern placental mammals (Boreoeutheria).

  17. Metabolism of bupropion by baboon hepatic and placental microsomes

    PubMed Central

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB. PMID:21570381

  18. Maternal micronutrients, omega-3 fatty acids, and placental PPARγ expression.

    PubMed

    Meher, Akshaya P; Joshi, Asmita A; Joshi, Sadhana R

    2014-07-01

    An altered one-carbon cycle is known to influence placental and fetal development. We hypothesize that deficiency of maternal micronutrients such as folic acid and vitamin B12 will lead to increased oxidative stress, reduced long-chain polyunsaturated fatty acids, and altered expression of peroxisome proliferator activated receptor (PPARγ) in the placenta, and omega-3 fatty acid supplementation to these diets will increase the expression of PPARγ. Female rats were divided into 5 groups: control, folic acid deficient, vitamin B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05) levels of placental docosahexaenoic acid, arachidonic acid, PPARγ expression and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF-α. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalized the expression of PPARγ and lowered the levels of placental TNF-α. In the case of supplementation to a folic acid deficient diet it lowered the levels of malonidialdehyde and placental IL-6 and TNF-α. This study has implications for fetal growth as oxidative stress, inflammation, and PPARγ are known to play a key role in the placental development.

  19. Relationship between placental traits and maternal intrinsic factors in sheep.

    PubMed

    Ocak, S; Ogun, S; Onder, H

    2013-06-01

    The relationship between maternal intrinsic factors and placental traits was investigated on three Southern Mediterranean breed of sheep; Cukurova Assaf (CA), Cukurova (C) and Cukurova Meat Sheep (CMS). The effect of parity and birth type were also considered in the study as a potential influencing factor. Our hypothesis was to show that while differences in placental traits between breed, parity and birth type affected lamb condition and survivability, its correlation to maternal intrinsic behavioral factors may also be a strong indicator. The study found breed related differences of maternal behavioral factors and also showed significant correlation of these behavioral patterns to various placental traits. It confirmed earlier findings that parity played a major role in the refinement of these behavioral patterns. Significant differences in birth weight (P<0.05), placental weight (P<0.05), number of cotyledons (P<0.01) and cotyledon length (P<0.05) was seen between breeds. Cotyledon weight (P<0.05), width (P<0.01) and length (P<0.05) were found to differ by parity. Breed and parity interaction significantly influenced cotyledon quantity. While we detected breed specific differences in relation to maternal intrinsic factors we also noticed significant variance within breeds to these behavioral patterns when linked to placental traits. Further study is required on the correlation between placental traits and postnatal behavior on not just the ewes but also on their lambs. This could have a significant bearing on how producers manage and maximize lamb survivability.

  20. Macrosomia has its roots in early placental development

    PubMed Central

    Schwartz, Nadav; Quant, Hayley S.; Sammel, Mary D.; PARRY, Samuel

    2014-01-01

    Introduction We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. Methods We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11–14 weeks and 18–24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ=PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 grams) and LGA (birth weight ≥90th percentile). Results The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71–0.77). Conclusions Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. PMID:25064071

  1. Placental mammal diversification and the Cretaceous-Tertiary boundary.

    PubMed

    Springer, Mark S; Murphy, William J; Eizirik, Eduardo; O'Brien, Stephen J

    2003-02-04

    Competing hypotheses for the timing of the placental mammal radiation focus on whether extant placental orders originated and diversified before or after the Cretaceous-Tertiary (KT) boundary. Molecular studies that have addressed this issue suffer from single calibration points, unwarranted assumptions about the molecular clock, andor taxon sampling that lacks representatives of all placental orders. We investigated this problem using the largest available molecular data set for placental mammals, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders. We used the ThorneKishino method, which permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree. Analyses that used different sets of fossil constraints, different priors for the base of Placentalia, and different data partitions all support interordinal divergences in the Cretaceous followed by intraordinal diversification mostly after the KT boundary. Four placental orders show intraordinal diversification that predates the KT boundary, but only by an average of 10 million years. In contrast to some molecular studies that date the rat-mouse split as old as 46 million years, our results show improved agreement with the fossil record and place this split at 16-23 million years. To test the hypothesis that molecular estimates of Cretaceous divergence times are an artifact of increased body size subsequent to the KT boundary, we also performed analyses with a "KT body size" taxon set. In these analyses, interordinal splits remained in the Cretaceous.

  2. Association between PAPP-A and placental thickness

    PubMed Central

    Mesdaghi-nia, Elaheh; Behrashi, Mitra; Saeidi, Arezoo; Abedzadeh Kalahroodi, Masoomeh; Sehat, Mojtaba

    2016-01-01

    Background: Measuring of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in first trimester can be a way for early detection of adverse prenatal outcome due to faulty placenta. Objective: The aim was to Determination of association between placental thickness in second trimester with low level of PAPP-A in first trimester. Materials and Methods: In this cohort study, serum PAPP-A of 187 pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤0.8 MOM were in exposed and others who had PAPP-A >0.8 defined as unexposed group. The criteria of placental thickness in ultrasound study was thickness of 4 cm or more than 50% of placental length. Results: Of 187 patients, 87 patients had PAPP-A >0.8 and 93 patients had PAPP-A ≤0.8. Women with low levels of PAPP-A in the first trimester, had an increased incidence placental thickness of 34.4%, whereas another group had about 15% (p=0.002). Also, PAPP-A levels had acceptable sensitivity and specificity for placental thickness detection (71.1% and 54.8%, respectively. Conclusion: Our study showed that serum level of PAPP-A generally was low (≤0.8) in women with a thick placenta (>4 cm or >50% of placental length). The first trimester of pregnancy measurement of PAPP-A will be more predictable for healthy placenta. PMID:27525326

  3. Placental angiogenesis in sheep models of compromised pregnancy

    PubMed Central

    Reynolds, Lawrence P; Borowicz, Pawel P; Vonnahme, Kimberly A; Johnson, Mary Lynn; Grazul-Bilska, Anna T; Redmer, Dale A; Caton, Joel S

    2005-01-01

    Because the placenta is the organ that transports nutrients, respiratory gases and wastes between the maternal and fetal systems, development of its vascular beds is essential to normal placental function, and thus in supporting normal fetal growth. Compromised fetal growth and development have adverse health consequences during the neonatal period and throughout adult life. To establish the role of placental angiogenesis in compromised pregnancies, we first evaluated the pattern of placental angiogenesis and expression of angiogenic factors throughout normal pregnancy. In addition, we and others have established a variety of sheep models to evaluate the effects on fetal growth of various factors including maternal nutrient excess or deprivation and specific nutrients, maternal age, maternal and fetal genotype, increased numbers of fetuses, environmental thermal stress, and high altitude (hypobaric) conditions. Although placental angiogenesis is altered in each of these models in which fetal growth is adversely affected, the specific effect on placental angiogenesis depends on the type of ‘stress’ to which the pregnancy is subjected, and also differs between the fetal and maternal systems and between genotypes. We believe that the models of compromised pregnancy and the methods described in this review will enable us to develop a much better understanding of the mechanisms responsible for alterations in placental vascular development. PMID:15760944

  4. Models for placental transfer studies of drugs.

    PubMed

    Bourget, P; Roulot, C; Fernandez, H

    1995-02-01

    Pregnancy is a specific dynamic state, and the potential usefulness of caring for a disorder in the fetus or the mother is now well established. Previously, pregnant women have been excluded from clinical trials, therefore only a few studies concerning evaluation of the pregestational metabolism or transplacental transfer (TPT) of drugs exist. Questions regarding the TPT of drugs are extensive and complex. For example, does TPT occur at a given gestational age, in the context of a particular type of pathology or when a drug is administered by a certain dosage regimen? If this is the case, what is the rapidity of penetration of the products of conception by the drug (bearing in mind its physicochemical characteristics)? Need harmful adverse effects on the child be feared? Is such penetration desirable, of no consequence, or dangerous? Does the possibility exist of accumulation in the placenta, fetal tissue or amniotic fluid? Should such findings modify the therapeutic regimens of drugs given to expectant mothers? Exchange mechanisms are complicated and models developed in vitro only partially reflect the actual equilibria that exist between mother and fetus. These include: (i) the perfused cotyledon model, which while simple, elegant and inexpensive, offers only a localised, restricted and fixed view of pregnancy; (ii) isolated anatomical fractions that are informative, but which straddle the border between physiology and pharmacology; and (iii) the necessary study, using microsomes, of placental metabolic capacity (enzyme cartography). In vivo study of TPT is based upon various multicompartmental pharmacokinetic models, some of which have been relatively validated in animals. The simplest indicator for the in vivo evaluation of TPT of a drug in the human species is determination of a feto-maternal blood concentration ratio (usually performed at the time of placental separation). However, the usefulness and limitations of this parameter are controversial, and it

  5. Factors affecting placental traits and relationships of placental traits with neonatal behaviour in goat.

    PubMed

    Konyali, A; Tölü, C; Daş, G; Savaş, T

    2007-02-01

    The relationships between placental characteristics and litter weight, factors affecting these characteristics, and the relationship between these characteristics and neonatal behaviour of goat kids were investigated in this study. The study was carried out over three consecutive years and animal material consisted of total 152 Turkish Saanen goats and their 230 kids. The results of the study demonstrated that there were positive correlations between litter weight (LW), cotyledon number (CN), placental weight (PW) (r=0.64 and 0.76, P<0.01), but there was negative correlation between LW and cotyledon density (CD) (r=-0.42, P<0.01). CD was negatively correlated with PW (r=-0.61, P<0.01). CN and PW were influenced by the parity of doe, birth type-sex combination, buck within years and year of the study. On the other hand, parity and birth type-sex combination had no effect on PE (P>0.05), but buck within year affected placental efficiency (P<0.01). CD was only influenced by the parity of doe (P<0.01). Duration of birth (D) was not significantly related with CD, but if CD declined, it prolonged (r=-0.23, P>0.05). There were strong relationships between CD and birth-to-standing (B-St), and CD and birth-to-suckling (B-Su) (r=-0.42 and -0.51, P=0.01 and P<0.01). The results of the present study have shown similarities to the findings of the studies in sheep. Further studies are required to investigate the basis of the relationship between CD and neonatal behaviour.

  6. Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein

    SciTech Connect

    Zolnierowicz, S.; Work, C.; Hutchison, K.; Fox, I.H. )

    1990-04-01

    The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-({sup 3}H)ethylcarboxamidoadenosine (({sup 3}H)NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-((3-cholamidopropyl)dimethylammonio)-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the ({sup 3}H)NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors.

  7. Proteolytic Processing Regulates Placental Growth Factor Activities*

    PubMed Central

    Hoffmann, Daniel C.; Willenborg, Sebastian; Koch, Manuel; Zwolanek, Daniela; Müller, Stefan; Becker, Ann-Kathrin A.; Metzger, Stephanie; Ehrbar, Martin; Kurschat, Peter; Hellmich, Martin; Hubbell, Jeffrey A.; Eming, Sabine A.

    2013-01-01

    Placental growth factor (PlGF) is a critical mediator of blood vessel formation, yet mechanisms of its action and regulation are incompletely understood. Here we demonstrate that proteolytic processing regulates the biological activity of PlGF. Specifically, we show that plasmin processing of PlGF-2 yields a protease-resistant core fragment comprising the vascular endothelial growth factor receptor-1 binding site but lacking the carboxyl-terminal domain encoding the heparin-binding domain and an 8-amino acid peptide encoded by exon 7. We have identified plasmin cleavage sites, generated a truncated PlGF118 isoform mimicking plasmin-processed PlGF, and explored its biological function in comparison with that of PlGF-1 and -2. The angiogenic responses induced by the diverse PlGF forms were distinct. Whereas PlGF-2 increased endothelial cell chemotaxis, vascular sprouting, and granulation tissue formation upon skin injury, these activities were abrogated following plasmin digestion. Investigation of PlGF/Neuropilin-1 binding and function suggests a critical role for heparin-binding domain/Neuropilin-1 interaction and its regulation by plasmin processing. Collectively, here we provide new mechanistic insights into the regulation of PlGF-2/Neuropilin-1-mediated tissue vascularization and growth. PMID:23645683

  8. Optimising sample collection for placental research.

    PubMed

    Burton, G J; Sebire, N J; Myatt, L; Tannetta, D; Wang, Y-L; Sadovsky, Y; Staff, A C; Redman, C W

    2014-01-01

    Biobanks provide an important repository of samples for research purposes. However, for those samples to reflect the in vivo state, and for experimental reliability and reproducibility, careful attention to collection, processing and storage is essential. This is particularly true for the placenta, which is potentially subjected to stressful conditions during delivery, and sample collection may be delayed owing to routine postpartum inspection by clinical staff. In addition, standardisation of the collection procedure enables samples to be shared among research groups, allowing larger datasets to be established. Here, we provide an evidence-based and experts' review of the factors surrounding collection that may influence data obtained from the human placenta. We outline particular requirements for specific techniques, and propose a protocol for optimal sample collection. We recognise that the relevance of these factors, and of the sample types collected to a particular study will depend on the research questions being addressed. We therefore anticipate that researchers will select from the protocol to meet their needs and resources available. Wherever possible, we encourage researchers to extend their collection to include additional samples that can be shared on an international collaborative basis, with appropriate informed consent, to raise the quality, as well as quantity, of placental research.

  9. Erasmus Darwin's enlightened views on placental function.

    PubMed

    Pijnenborg, R; Vercruysse, L

    2007-01-01

    In his major work "Zoonomia", Erasmus Darwin (1731-1802) devoted one chapter to the placenta, in which the new knowledge of the recently discovered element oxygen was applied to the functioning of this organ. He considered the "cavities" or "lacunae" in the placenta as the main areas for oxygenation of the fetal blood, as he thought them to be structurally comparable to the lungs and the gills of fish. He obviously was aware of species differences in the uterine arterial blood supply to the placenta between humans and cows, assuming a higher contractility of the vasculature in the latter species. The new evidence for a primarily respiratory role overshadowed ideas of a possible nutritive function of the placenta. Since Hunter's definitive demonstration of separate maternal and fetal blood circulations, nutritive functions of the placenta needed to be explained by transmembrane transport processes, which were unknown at that time. Instead Erasmus Darwin erroneously considered the amniotic fluid as the main source of nutrients for the fetus. His understanding of placental respiration found expression in his long poem on the history of life on earth.

  10. Evolutionary perspectives into placental biology and disease.

    PubMed

    Chuong, Edward B; Hannibal, Roberta L; Green, Sherril L; Baker, Julie C

    2013-12-01

    In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal-fetal conflict shapes both basic placental and reproductive biology - in all species - will provide key insights into diseases of pregnancy.

  11. Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.

    PubMed

    Lager, S; Aye, I L M H; Gaccioli, F; Ramirez, V I; Jansson, T; Powell, T L

    2014-12-01

    Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Placental tissue was collected from healthy, term pregnancies (n = 15 no-labor; n = 12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFĸB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFĸB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    PubMed Central

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  13. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    PubMed

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats. © 2015 The Author(s).

  14. Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

    PubMed Central

    Baptiste-Roberts, Kesha; Salafia, Carolyn M; Nicholson, Wanda K; Duggan, Anne; Wang, Nae-Yuh; Brancati, Frederick L

    2008-01-01

    Background Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area. Methods We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as < 10th percentile and hypertrophy as > 90th percentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a) predictors of restricted growth (vs. normal) and (b) predictors of hypertrophic growth (vs. normal). Results Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth. Conclusion Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms. PMID:18811957

  15. Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy.

    PubMed

    Dias-Junior, Carlos A; Chen, Juanjuan; Cui, Ning; Chiang, Charles L; Zhu, Minglin; Ren, Zongli; Possomato-Vieira, Jose S; Khalil, Raouf A

    2017-09-11

    Preeclampsia is a form of hypertension-in-pregnancy (HTN-Preg) with unclear mechanism. Generalized reduction of uterine perfusion pressure (RUPP) could be an initiating event leading to uteroplacental ischemia, angiogenic imbalance, and HTN-Preg. Additional regional differences in uteroplacental blood flow could further affect the pregnancy outcome and increase the risk of preeclampsia in twin or multiple pregnancy, but the mechanisms involved are unclear. To test the hypothesis that regional differences in angiogenic balance and matrix metalloproteinases (MMPs) underlie regional uteroplacental vascularization and feto-placental development, we compared fetal and placental growth, and placental and myoendometrial vascularization in the proximal, middle and distal regions of the uterus (in relation to the iliac bifurcation) in normal pregnant (Preg) and RUPP rats. Maternal blood pressure and plasma anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1)/placenta growth factor (PIGF) ratio were higher, and average placentae number, placenta weight, litter size, and pup weight were less in RUPP than Preg rats. The placenta and pup number and weight were reduced, while the number and diameter of placental and adjacent myoendometrial arteries, and MMP-2 and MMP-9 levels/activity were increased, and sFlt-1/PlGF ratio was decreased in distal vs proximal uterus of Preg rats. In RUPP rats, the placenta and pup number and weight, the number and diameter of placental and myoendometrial arteries, and MMP-2 and -9 levels/activity were decreased, and sFlt-1/PlGF ratio was increased in distal vs proximal uterus. Treatment with sFlt-1 or RUPP placenta extract decreased MMP-2 and MMP-9 in distal segments of Preg uterus, and treatment with PIGF or Preg placenta extract restored MMP levels in distal segments of RUPP uterus. Thus, in addition to the general reduction in placental and fetal growth during uteroplacental ischemia, localized angiogenic imbalance and diminished MMP-2

  16. Effect of pregestational diabetes mellitus on first trimester placental characteristics: three-dimensional placental volume and power Doppler indices.

    PubMed

    Gonzalez Gonzalez, N L; Gonzalez Davila, E; Castro, A; Padron, E; Plasencia, W

    2014-03-01

    To investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester. This was a prospective case-control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β human chorionic gonadotrophin (β-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group. 3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p < 0.02) and negatively correlated with the degree of maternal metabolic control at first trimester. Pregestational DM induces demonstrable alterations in first trimester placental development, with significantly reduced placental vascularization indices and PAPP-A values. This effect is independent of the later development of PAHC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

    PubMed Central

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Diener, Pierre-André; Maeder-Althaus, Xenia; Maurizi, Lionel; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula

    2015-01-01

    Background Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles. Methods We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue. Conclusions Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers. Citation Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human

  18. Human placental lactogen decreases regional blood flow in anesthetized pigs.

    PubMed

    Grossini, E; Molinari, C; Battaglia, A; Mary, D A S G; Ribichini, F; Surico, N; Vacca, G

    2006-01-01

    In 22 pigs anesthetized with sodium pentobarbitone, changes in blood flow caused by infusion of human placental lactogen into the left renal, external iliac, and anterior descending coronary arteries were assessed using electromagnetic flowmeters. In 17 pigs, infusion of human placental lactogen whilst keeping the heart rate and arterial pressure constant decreased coronary, renal and iliac flow. In 5 additional pigs, increasing the dose of human placental lactogen produced a dose-related decrease in regional blood flow. The mechanisms of the above response were studied in 15 of the 17 pigs by repeating the experiment of infusion. The human placental lactogen-induced decrease in regional blood flow was not affected by blockade of cholinergic receptors (5 pigs) or of alpha-adrenergic receptors (5 pigs), but it was abolished by blockade of beta2-adrenergic receptors (5 pigs). The present study showed that intra-arterial infusion of human placental lactogen primarily decreased coronary, renal and iliac blood flow. The mechanism of this response was shown to be due to the inhibition of a vasodilatory beta2-adrenergic receptor-mediated effect.

  19. Thromboembolic diseases in families of women with placental abruption.

    PubMed

    Peltier, Morgan R; Ananth, Cande V; Oyelese, Yinka; Vintzileos, Anthony M

    2009-09-01

    We explored the incidence of thromboembolic disease in relatives of women diagnosed with placental abruption, a condition that may be related to disordered coagulation. Using data from a multicenter, case-control study of placental abruption, we assessed thromboembolic diseases in first-degree male and female relatives of women with and without abruption. The analysis was restricted to biologic parents and full siblings, below 65 years of age, and corrected for familial clustering. The prevalence of thromboembolic disease was 7.5% in 852 relatives of 212 placental abruption cases and 4.8% in 792 relatives of 206 controls. This increased risk was driven by an association among sisters of abruption probands (odds ratio = 6.8 [95% confidence interval = 1.8-26.0]), and to a lesser extent, among mothers (2.0 [1.0-4.2]). The risk of thromboembolic diseases was similar among the male relatives of placental abruption cases and controls. These data suggest that thromboembolic diseases aggregate within female relatives of women with placental abruption.

  20. Nitric oxide and oxidative stress in placental explant cultures.

    PubMed

    Goncalves, Juvic M; Casart, Ysabel C; Camejo, María I

    2016-01-01

    Placental explant culture, and cellular cytolysis and cellular differentiation have been previously studied. However, oxidative stress and nitric oxide profiles have not been evaluated in these systems. The aim of this study was to determine the release of lipid peroxidation and nitric oxide from placental explants cultured over a seven day period. Placental explants were maintained for seven days in culture and the medium was changed every 24 hours. The response was assessed in terms of syncytiotrophoblast differentiation (human chorionic gonadotropin, hCG), cellular cytolysis (lactate dehydrogenase, LDH), oxidative stress (thiobarbituric acid reactive substances, TBARS), and nitric oxide (NO). Levels of hCG increased progressively from day two to attain its highest level on days four and five after which it decreased gradually. In contrast, the levels of LDH, TBARS, and NO were elevated in the early days of placental culture when new syncytiotrophoblast from cytotrophoblast were forming and also in the last days of culture when tissue was declining. In conclusion, the levels of NO and lipid peroxidation follow a pattern similar to LDH and contrary to hCG. Future placental explant studies to evaluate oxidative stress and NO should consider the physiological changes inherent during the time of culture.

  1. A higher-level MRP supertree of placental mammals

    PubMed Central

    Beck, Robin MD; Bininda-Emonds, Olaf RP; Cardillo, Marcel; Liu, Fu-Guo Robert; Purvis, Andy

    2006-01-01

    Background The higher-level phylogeny of placental mammals has long been a phylogenetic Gordian knot, with disagreement about both the precise contents of, and relationships between, the extant orders. A recent MRP supertree that favoured 'outdated' hypotheses (notably, monophyly of both Artiodactyla and Lipotyphla) has been heavily criticised for including low-quality and redundant data. We apply a stringent data selection protocol designed to minimise these problems to a much-expanded data set of morphological, molecular and combined source trees, to produce a supertree that includes every family of extant placental mammals. Results The supertree is well-resolved and supports both polyphyly of Lipotyphla and paraphyly of Artiodactyla with respect to Cetacea. The existence of four 'superorders' – Afrotheria, Xenarthra, Laurasiatheria and Euarchontoglires – is also supported. The topology is highly congruent with recent (molecular) phylogenetic analyses of placental mammals, but is considerably more comprehensive, being the first phylogeny to include all 113 extant families without making a priori assumptions of suprafamilial monophyly. Subsidiary analyses reveal that the data selection protocol played a key role in the major changes relative to a previously published higher-level supertree of placentals. Conclusion The supertree should provide a useful framework for hypothesis testing in phylogenetic comparative biology, and supports the idea that biogeography has played a crucial role in the evolution of placental mammals. Our results demonstrate the importance of minimising poor and redundant data when constructing supertrees. PMID:17101039

  2. Placental leptin gene methylation and macrosomia during normal pregnancy.

    PubMed

    Xu, Xinyun; Yang, Xinjun; Liu, Ziwei; Wu, Kele; Liu, Zheng; Lin, Chong; Wang, Yuhuan; Yan, Hongtao

    2014-03-01

    The present study examined the placental leptin (LEP) DNA methylation and mRNA levels in macrosomic infants from normal pregnancies. In total, 49 neonates with macrosomia, i.e., high birth weights of ≥ 4,000 g, and 52 neonates with normal birth weights between 2,500 g and 4,000 g were recruited from The Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, Zhejiang) in China. Placental LEP promoter methylation and LEP transcript levels were determined by Sequenom MassARRAY and quantitative PCR, respectively. LEP promoter methylation and mRNA levels were not significantly different between the individuals with macrosomia and the controls. However, stratification revealed that individual CpG dinucleotides were hypermethylated in macrosomia (P<0.05) in primiparous females and at 39 weeks of gestation (P<0.05). Variations in methylation did not affect placental LEP expression. It was concluded that the methylation of the placental LEP promoter was altered during a specific gestational period in macrosomia following a normal pregnancy and under certain conditions. However, placental LEP expression was not affected.

  3. Acute diabetes insipidus mediated by vasopressinase after placental abruption.

    PubMed

    Wallia, Amisha; Bizhanova, Aigerim; Huang, Wenyu; Goldsmith, Susan L; Gossett, Dana R; Kopp, Peter

    2013-03-01

    Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

  4. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

    PubMed Central

    2011-01-01

    Objective To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation. Research design and methods One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM) positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT) in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH), gestational DM (GDM) or overt DM (DM). Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin. Results Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon. Conclusion Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus. PMID:21831283

  5. Heterogeneous Models Place the Root of the Placental Mammal Phylogeny

    PubMed Central

    Morgan, Claire C.; Foster, Peter G.; Webb, Andrew E.; Pisani, Davide; McInerney, James O.; O’Connell, Mary J.

    2013-01-01

    Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root. PMID:23813979

  6. Placental pathologies in fetal MRI with pathohistological correlation.

    PubMed

    Linduska, N; Dekan, S; Messerschmidt, A; Kasprian, G; Brugger, P C; Chalubinski, K; Weber, M; Prayer, D

    2009-06-01

    The purpose of this study was to evaluate whether currently available fetal Magnetic Resonance Imaging (MRI/MR) techniques are sufficient for the assessment of placental pathologies. We hypothesized that placental pathologies as detected and evaluated by MRI, would correlate with histological findings. In a retrospective study, 45 singleton pregnancies from 19 to 35 gestational weeks, with placental pathologies on MR scans, were included. MRI was performed on a 1.5T unit using T2-, T1-, and diffusion-weighted and echo-planar sequences. Pathologies were categorized into infarction with/without hemorrhagic components, subchorionic/intervillous thrombi/hemorrhages, retroplacental hematoma, massive perivillous fibrin deposition, and chorioamnionitis. Pathohistological examination was performed postnatally within a median of seven days between MR examination and delivery. Pathologically, 26 placentas showed infarctions (96.2% on MR scans), two retroplacental hematomas were detected by MRI and confirmed by pathology, and 9 of 14 subchorionic hematomas were confirmed. Six of eight intervillous hemorrhages were seen on MRI, and three of six cases of severe chorioamnionitis were diagnosed prenatally. Placental hemorrhages (retroplacental hematoma, intervillous thrombi, subchorionic hematoma), and ischemic lesions could be detected with fetal MRI, while chorioamnionitis and even massive perivillous fibrin deposition showed few signal changes, probably reflecting small macroscopic changes in the placenta. Fetal MRI, therefore, seems to be a promising tool for the assessment of placental insufficiency.

  7. Heterogeneous models place the root of the placental mammal phylogeny.

    PubMed

    Morgan, Claire C; Foster, Peter G; Webb, Andrew E; Pisani, Davide; McInerney, James O; O'Connell, Mary J

    2013-09-01

    Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root.

  8. Adenylate kinase locus 1 polymorphism and feto-placental development.

    PubMed

    Fulvia, Gloria-Bottini; Antonio, Pietroiusti; Anna, Neri; Patrizia, Saccucci; Ada, Amante; Egidio, Bottini; Andrea, Magrini

    2011-12-01

    Recently our group has found that the correlation between birth weight and placental weight - an index of a balanced feto-placental unit development - is influenced by genetic factors. Since adenylate kinase locus 1 (AK₁) is a polymorphic enzyme that plays an important role in the synthesis of nucleotides required for many metabolic functions, we have investigated the possible role of its genetic variability in the correlation between birth weight and placental weight. 342 consecutive healthy newborn infants from the population of Rome (Italy) and 286 puerperae from another population from Central Italy were studied. The correlation coefficient between birth weight and placental weight is much higher in infants with low activity AK₁2-1 phenotype than in those with high activity AK₁1 phenotype. The difference between AK₁ and AK₁2-1 is well marked only in newborns with a gestational age greater than 38 weeks and it is not influenced by sex, maternal age and maternal smoking. A similar pattern is observed with maternal AK₁ phenotype. These results suggest that the difference in enzymatic activity between AK₁ phenotypes influencing the equilibrium among ATP, ADP, AMP and adenosine could have an important role in a balanced development of feto-placental unit. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Rates of Molecular Evolution Suggest Natural History of Life History Traits and a Post-K-Pg Nocturnal Bottleneck of Placentals.

    PubMed

    Wu, Jiaqi; Yonezawa, Takahiro; Kishino, Hirohisa

    2017-10-09

    Life history and behavioral traits are often difficult to discern from the fossil record, but evolutionary rates of genes and their changes over time can be inferred from extant genomic data. Under the neutral theory, molecular evolutionary rate is a product of mutation rate and the proportion of neutral mutations [1, 2]. Mutation rates may be shared across the genome, whereas proportions of neutral mutations vary among genes because functional constraints vary. By analyzing evolutionary rates of 1,185 genes in a phylogeny of 89 mammals, we extracted historical profiles of functional constraints on these rates in the form of gene-branch interactions. By applying a novel statistical approach to these profiles, we reconstructed the history of ten discrete traits related to activity, diet, and social behaviors. Our results indicate that the ancestor of placental mammals was solitary, seasonally breeding, insectivorous, and likely nocturnal. The results suggest placental diversification began 10-20 million years before the K-Pg boundary (66 million years ago), with some ancestors of extant placental mammals becoming diurnal and adapted to different diets. However, from the Paleocene to the Eocene-Oligocene transition (EOT, 33.9 mya), we detect a post-K-Pg nocturnal bottleneck where all ancestral lineages of extant placentals were nocturnal. Although diurnal placentals may have existed during the elevated global temperatures of the Paleocene-Eocene thermal maximum [3], we hypothesize that diurnal placentals were selectively extirpated during or after the global cooling of the EOT, whereas some nocturnal lineages survived due to preadaptations to cold environments [4]. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss

    PubMed Central

    Winship, Amy; Correia, Jeanne; Krishnan, Tara; Menkhorst, Ellen; Cuman, Carly; Zhang, Jian-Guo; Nicola, Nicos A.; Dimitriadis, Evdokia

    2015-01-01

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRα were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRα antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy. PMID:26272398

  11. Activity of anandamide (AEA) metabolic enzymes in rat placental bed.

    PubMed

    Fonseca, B M; Battista, N; Correia-da-Silva, G; Rapino, C; Maccarrone, M; Teixeira, N A

    2014-11-01

    Endocannabinoids are endogenous lipid mediators, with anandamide (AEA) being the first member identified. It is now widely accepted that AEA influences early pregnancy events and its levels, which primarily depend on its synthesis by an N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and degradation by a fatty acid amide hydrolase (FAAH), must be tightly regulated. Previous studies demonstrated that AEA levels require in situ regulation of these respective metabolic enzymes, and thus, any disturbance in AEA levels may impact maternal remodeling processes occurring during placental development. In this study, the activities of the AEA-metabolic enzymes that result in the establishment of proper local AEA levels during rat gestation were examined. Here, we demonstrate that during placentation NAPE-PLD and FAAH activities change in a temporal manner. Our findings suggest that NAPE-PLD and FAAH create the appropriate AEA levels required for tissue remodeling in the placental bed, a process essential to pregnancy maintenance.

  12. Placental lesions in a case of DiGeorge sequence.

    PubMed

    Fulcheri, E; Gualco, M; Delfino, F; Pantarotto, M F

    2006-01-01

    This work describes some placental alterations found in a partial form of DiGeorge sequence, namely, hypoplasia of a cord artery with internal calcification of an extensive endoluminal thrombosis, and widespread calcification of microthrombi in the arteries of the second and third order villous branches. Hypoplasia of a cord artery is a relatively rare event, and is also associated with malformations of the gastroenteric and cardiovascular system, as sometimes described in the DiGeorge sequence. Interesting placental alterations are reported and their likely physiopathologic basis and pathogenic correlation discussed in order to give a better and more comprehensive picture of the DiGeorge sequence in which the correlated placental alterations are not sufficiently known.

  13. Parallel adaptive radiations in two major clades of placental mammals.

    PubMed

    Madsen, O; Scally, M; Douady, C J; Kao, D J; DeBry, R W; Adkins, R; Amrine, H M; Stanhope, M J; de Jong, W W; Springer, M S

    2001-02-01

    Higher level relationships among placental mammals, as well as the historical biogeography and morphological diversification of this group, remain unclear. Here we analyse independent molecular data sets, having aligned lengths of DNA of 5,708 and 2,947 base pairs, respectively, for all orders of placental mammals. Phylogenetic analyses resolve placental orders into four groups: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. The first three groups are consistently monophyletic with different methods of analysis. Euarchonta plus Glires is monophyletic or paraphyletic depending on the phylogenetic method. A unique nine-base-pair deletion in exon 11 of the BRCA1 gene provides additional support for the monophyly of Afrotheria, which includes proboscideans, sirenians, hyracoids, tubulidentates, macroscelideans, chrysochlorids and tenrecids. Laurasiatheria contains cetartiodactyls, perissodactyls, carnivores, pangolins, bats and eulipotyphlan insectivores. Parallel adaptive radiations have occurred within Laurasiatheria and Afrotheria. In each group, there are aquatic, ungulate and insectivore-like forms.

  14. Clinical use of placental hormones in pregnancy management.

    PubMed

    De Bonis, M; Vellucci, F L; Di Tommaso, M; Voltolini, C; Torricelli, M; Petraglia, F

    2012-09-01

    Across human pregnancy, placenta represents a transit of oxygen and nutrients from the mother to the fetus and actively produces a large number of hormones that serve to regulate and balance maternal and fetal physiology. An abnormal secretion of placental hormones may be part of the pathogenesis of the main obstetric syndrome, from early to late pregnancy, in particular chromosomopathies, miscarriage, gestational trophoblastic diseases, preeclampsia, gestational diabetes, and pre-term delivery. The possibility to measure placental hormones represents an important tool not only for the diagnosis and management of gestational disorders, but it is also fundamental in the early identification of women at risk for these pregnancy complications. In the last decades, the use of ultrasound examination has provided additional biophysical markers, improving the early diagnosis of gestational diseases. In conclusion, while few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool.

  15. Human placental coated vesicles contain receptor-bound transferrin.

    PubMed Central

    Booth, A G; Wilson, M J

    1981-01-01

    Human placental coated vesicles have been purified by a method involving sucrose-density-gradient centrifugation and treatment with wheat-germ agglutinin. These preparations were free of contamination by placental microvillus fragments. Crossed immunoelectrophoresis demonstrated that the coated vesicles contained a single serum protein, which was identified as transferrin. This transferrin was only observed after the vesicles were treated with a non-ionic detergent, and its behaviour during crossed hydrophobic-interaction immunoelectrophoresis suggested that a large proportion of it was receptor-bound. No other serum proteins, including immunoglobulin G, could be detected in these preparations. Receptor-bound transferrin was the only antigen common to placental coated vesicles and microvilli, implying that other plasma-membrane proteins are excluded from the region of membrane involved in coated-vesicle formation. Images PLATE 2 PLATE 1 Fig. 1. Fig. 2. Fig. 3. PMID:6272755

  16. Basal plate plaque: a novel organising placental thrombotic process.

    PubMed

    Fitzgerald, Brendan; Shannon, Patrick; Kingdom, John; Keating, Sarah

    2011-08-01

    In contrast to thrombi and haematomas at other body sites, thrombi in the placental intervillous space are not traditionally known to undergo organisation. This report presents 11 examples of a form of organising thrombotic process that develops as a plaque on the foetal aspect of the basal plate. Originally identified in the placenta of a foetus showing severe intrauterine growth restriction, further examples of this lesion, which we term a 'basal plate plaque', show a spectrum of placental involvement. Small lesions appear to occur at points of localised stasis at the basal plate (eg, at edges of anchoring villi or in small basal plate depressions). Large areas of involvement, as seen in the original case, may be pathological markers of more generalised disturbances in placental circulation or of hypercoagulability in the intervillous space. Large basal plate plaques may therefore prove to be diagnostically significant and should be reported.

  17. [Cellular components and placental alkaline phosphatase in Trypanosoma cruzi infection ].

    PubMed

    Sartori, Maria José; Mezzano, Luciana; Lin, Susana; Repossi, Gastón; Fabro, Sofía P

    2005-01-01

    Trypanosoma cruzi induces changes in the protein pattern of human placenta syncytiotrophoblast. Placental alkaline phosphatase (PLAP) is a glycoenzyme anchored to the membrane by a glycosyl-phosphatidylinositol molecule. PLAP activity and its presence was altered by the parasite in cultures of human placental villi and HEp2 cells with T.cruzi. The cells treated before the cultures with agents which affect PILAP or glycosyl-phosphatidylinositol (antibodies, PL-C, genistein, lithium) presented less parasitic invasion than the control ones. It was also observed a modification in the pattern of actine filaments of the host cells infected. We concluded that PLAP would participate in the process of T. cruzi invasion into placental syncitiotrophoblast cells, by a mechanism that involves hydrolysis of the glycosyl-phosphatidylinositol molecules, the activation of tyrosine kinase proteins, the increase of cytosolic calcium and the rearrangement of actine filaments of the host cells.

  18. The feto-placental endothelium in pregnancy pathologies.

    PubMed

    Wadsack, Christian; Desoye, Gernot; Hiden, Ursula

    2012-05-01

    This review aims to provide a comprehensive summary of the aspects of endothelial and vascular dysfunction in the feto-placental vasculature occurring in pregnancy pathologies. This endothelium is continuous with the fetal circulation. Its function and potential dysfunction in pathologies will have a profound impact on fetal development. Gestational diabetes mellitus represents one of these pathologies, in which its associated metabolic derangements will alter feto-placental endothelial functions. These, in turn, may result in functional changes of the placenta, which may entail impaired fetal development. By contrast, changes in the feto-placental vasculature observed in cases of fetal growth restriction and preeclampsia may be causative (fetal growth restriction) or secondary (preeclampsia) for the pathology.

  19. Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

    PubMed Central

    Souza, Mariângela Alves; de Lourdes Brizot, Maria; Biancolin, Sckarlet Ernandes; Schultz, Regina; de Carvalho, Mário Henrique Burlacchini; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2017-01-01

    OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies. PMID:28591337

  20. Interleukin-11 alters placentation and causes preeclampsia features in mice

    PubMed Central

    Winship, Amy L.; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J.; Dimitriadis, Evdokia

    2015-01-01

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal–fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

  1. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

    PubMed

    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-04-01

    Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (P<0.01) and diastolic blood pressure (P<0.05) in preeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (P<0.001). Thrombomodulin expression correlated positively with matrix metalloproteinase expression (P<0.01) in preeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on

  2. Apelin in Normal Pregnancy and Pregnancies Complicated by Placental Insufficiency.

    PubMed

    Van Mieghem, Tim; Doherty, Anne; Baczyk, Dora; Drewlo, Sascha; Baud, David; Carvalho, Jose; Kingdom, John

    2016-08-01

    Apelin is a potent inotropic agent and causes endothelium-mediated vasodilation. Its cardiovascular profile suggests a role in the regulation of gestational hemodynamics. We longitudinally assessed maternal serum apelin levels and hemodynamics (cardiac output and total peripheral resistance) between 20 and 34 weeks gestation in 18 women at high risk of placental dysfunction. Placental apelin staining was assessed by immunohistochemistry in placentas from uncomplicated pregnancies (n = 6), preterm deliveries (n = 6), preeclampsia (PET, n = 8), and isolated intrauterine growth restriction (IUGR, n = 8). Placental apelin gene expression was assessed by quantitative polymerase chain reaction. In the high-risk cohort, 4 fetuses developed isolated IUGR and 6 women developed PET. We obtained a median of 5 (range 2-9) hemodynamic and apelin measurements per woman. Apelin levels throughout gestation were best fitted by a quadratic curve. Apelin levels between 20 and 26 weeks gestation correlated with total peripheral resistance (r = .57, P = .01) and showed a trend toward an inverse correlation with stroke volume (r = -.42, P = .08). Apelin serum levels were 30% lower in pregnancies complicated by IUGR than in uncomplicated pregnancies or in women with preeclampsia (P = .009). Placental apelin gene expression was similar in IUGR, PET, preterm, and term normal placentas. Apelin staining was seen both in syncytiotrophoblast and stroma of the placental villi. In IUGR placentas, apelin staining was strongly decreased in both compartments compared to normals. Preeclamptic placentas showed an intermediate staining. Apelin levels mirror the cardiovascular changes seen in pregnancy. Serum and placental apelin levels are decreased in IUGR. © The Author(s) 2016.

  3. Animal models of human placentation--a review.

    PubMed

    Carter, A M

    2007-04-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.

  4. Sex-Specific Placental Responses in Fetal Development

    PubMed Central

    2015-01-01

    The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration. PMID:26241064

  5. Macrosomia has its roots in early placental development.

    PubMed

    Schwartz, N; Quant, H S; Sammel, M D; Parry, S

    2014-09-01

    We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. HIV-1 Nef breaches placental barrier in rat model.

    PubMed

    Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, Monika; Tripathi, Raj Kamal

    2012-01-01

    The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors.

  7. Oral bacteria in placental tissues: increased molecular detection in pregnant periodontitis patients.

    PubMed

    Blanc, V; O'Valle, F; Pozo, E; Puertas, A; León, R; Mesa, F

    2015-10-01

    The objective of this study was to identify the DNA of oral bacteria in placental samples from women with and without periodontitis who had or had not had preterm births and/or low birthweight (PB/LBW) neonates. Data were gathered from 57 puerperal women in relation to socio-demographic, gynaecological, and periodontal variables and to placental histomorphology. Fifty-seven biopsies, 28 from mothers with periodontitis, were taken aseptically from preterm placentas (n = 36) and from full-term placentas (n = 21). Total DNA was extracted, and the presence of 15 oral bacteria was assessed using Nested-PCR. The placentas from women with periodontitis showed a higher prevalence of periodontopathogens compared to those from women without periodontitis (P = 0.009). Samples showed low prevalences of Actinomyces israelii, Parvimonas micra and Tannerella forsythia. An association was found between Eikenella corrodens in placenta and periodontitis (P = 0.002). The most ubiquitous bacterium, Fusobacterium nucleatum, was more prevalent in mothers with periodontitis and PB/LBW (P = 0.033). Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were not detected. These results, along with previous findings, show that oral bacteria may be normally present in the placenta, however, the levels of certain oral pathogens in the placenta would highly depend on the mother's periodontal state. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Sources for Comparative Studies of Placentation. II. Genomic Resources

    PubMed Central

    Wildman, Derek E.

    2008-01-01

    The genomes of dozens of placental mammal species are now publicly available. These genome sequences have the potential to provide insight into the development and evolution of the placenta. In particular, the variable anatomy of the placenta has likely been affected by natural selection on the genomes of living and extinct mammals. In this note the current availability of mammal genome sequences is reviewed, and strengths and limitations of these data are discussed. Additionally, museums, zoos, and commercial entities are available to provide genomic resources to the placental research community. Recommendations for tissue storage conditions of placentas in genomic research are given. PMID:18155141

  9. Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

    PubMed

    Souza, Rodrigo M; Ataíde, Ricardo; Dombrowski, Jamille G; Ippólito, Vanessa; Aitken, Elizabeth H; Valle, Suiane N; Álvarez, José M; Epiphanio, Sabrina; Epiphânio, Sabrina; Marinho, Claudio R F

    2013-01-01

    Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41), P. vivax exposure (n = 59) or P. falciparum exposure (n = 19). We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045), placental barrier thickness (OR, 25.59, P = 0.021) and mononuclear cells (OR, 4.02, P = 0.046) were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A vivax-score was

  10. Infant sex-specific placental cadmium and DNA methylation associations

    SciTech Connect

    Mohanty, April F.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Afsharinejad, Zahra; Burbacher, Thomas M.; Siscovick, David S.; and others

    2015-04-15

    Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these

  11. Placental mesenchymal dysplasia associated with hepatic and pulmonary hamartoma.

    PubMed

    Tortoledo, Maria; Galindo, A; Ibarrola, C

    2010-01-01

    This report describes a 31-week stillborn female infant with placental mesenchymal dysplasia (PMD) in association with hepatic mesenchymal hamartoma (HMH) and pulmonary hamartoma. Placental mesenchymal dysplasia was initially misdiagnosed as a partial mole. However, histologically, no trophoblastic proliferation or inclusions were observed. Differential diagnosis of the hepatic mass with similar tumors is discussed. To our knowledge, this is the first case of lung hamartoma reported in a fetus and the first case related to PMD and HMH. A common anomalous development of the mesoderm, a reparative post-injury process and a genetic mechanism, have been proposed to explain their pathogenesis.

  12. Relation between placental site and length of gestation.

    PubMed

    Harris, V G

    1975-07-01

    Two theories related to uterine action have been brought together to see whether the site of placental implantation influences the onset of labour: (1) that uterine contractions begin asymmetrically from a "pacemaker" in one uterine horn, and (2) that progesterone from the placenta blocks myometrial contractility primarily at the site of implantation. Case records were examined of 182 patients who had placental locations performed and who had a spontaneous onset of labour. Where the placenta was implanted in the right upper quadrant of the uterus labour occurred on average four days sooner than when it was implanted in the left upper quandrant: the difference was statistically significant.

  13. Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease.

    PubMed

    Stefanovic, Vladisav; Cukuranovic, Rade; Dolicanin, Zana; Cukuranovic, Jovana; Stojnev, Slavica; Bogdanovic, Dragan; Rajic, Milena; Kocic, Gordana

    2015-08-01

    Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74 yr (53-87) and 73 yr (66-83) in controls. In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2 µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6 mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80 pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90 pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0 pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5 pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.

  14. IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of lipids in the growth and development of feto-placental unit; placental nutrient sensing; placental research to solve clinical problems--a translational approach.

    PubMed

    Acharya, G; Albrecht, C; Benton, S J; Cotechini, T; Dechend, R; Dilworth, M R; Duttaroy, A K; Grotmol, T; Heazell, A E; Jansson, T; Johnstone, E D; Jones, H N; Jones, R L; Lager, S; Laine, K; Nagirnaja, L; Nystad, M; Powell, T; Redman, C; Sadovsky, Y; Sibley, C; Troisi, R; Wadsack, C; Westwood, M; Lash, G E

    2012-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, four of which are summarized in this report. These workshops related to both basic science and clinical research into placental growth and nutrient sensing and were divided into 1) placenta: predicting future health; 2) roles of lipids in the growth and development of feto-placental unit; 3) placental nutrient sensing; 4) placental research to solve clinical problems: a translational approach. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Human placental lactogen mRNA and its structural genes during pregnancy: quantitation with a complementary DNA.

    PubMed Central

    McWilliams, D; Callahan, R C; Boime, I

    1977-01-01

    A complementary DNA (cDNA) strand was transcribed from human placental lactogen (hPL) mRNA. Based on alkaline sucrose gradient centrifugation, the size of the cDNA was about 8 S, which would represent at least 80% of the hPL mRNA. Previously we showed that four to five times more hPL was synthesized in cell-free extracts derived from term as compared to first trimester placentas. Hybridization of the cDNA with RNA derived from placental tissue revealed that there was about four times more hPL mRNA sequences in total RNA from term placenta than in a comparable quantity of total first trimester RNA. Only background hybridization was observed when the cDNA was incubated with RNA prepared from human kidney. To test if this differential accumulation of hPL mRNA was the result of an amplification of hPL genes, we hybridized the labeled cDNA with cellular DNA from first trimester and term placentas and with DNA isolated from human brain. In all cases, the amount of hPL sequences was approximately two copies per haploid genome. Thus, the enhanced synthesis of hPL mRNA appears to result from a transcriptional activation rather than an amplification of the hPL gene. The increase likely reflects placental differentiation in which the proportion of syncytial trophoblast increases at term. Images PMID:66681

  16. 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% 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. © 2016 by the Society for the Study of Reproduction, Inc.

  17. IFPA Meeting 2012 Workshop Report I: comparative placentation and animal models, advanced techniques in placental histopathology, human pluripotent stem cells as a model for trophoblast differentiation.

    PubMed

    Ackerman, W E; Carter, A M; De Mestre, A M; Golos, T G; Jeschke, U; Kusakabe, K; Laurent, L C; Parast, M M; Roberts, R M; Robinson, J M; Rutherford, J; Soma, H; Takizawa, T; Ui-Tei, K; Lash, G E

    2013-03-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of models and technical issues involved in placenta research: 1) comparative placentation and animal models; 2) advanced techniques in placental histopathology; 3) human pluripotent stem cells as a model for trophoblast differentiation.

  18. Notch signalling in placental development and gestational diseases.

    PubMed

    Haider, S; Pollheimer, J; Knöfler, M

    2017-01-16

    Activation of Notch signalling upon cell-cell contact of neighbouring cells controls a plethora of cellular processes such as stem cell maintenance, cell lineage determination, cell proliferation, and survival. Accumulating evidence suggests that the pathway also critically regulates these events during placental development and differentiation. Herein, we summarize our present knowledge about Notch signalling in murine and human placentation and discuss its potential role in the pathophysiology of gestational disorders. Studies in mice suggest that Notch controls trophectoderm formation, decidualization, placental branching morphogenesis and endovascular trophoblast invasion. In humans, the particular signalling cascade promotes formation of the extravillous trophoblast lineage and regulates trophoblast proliferation, survival and differentiation. Expression patterns as well as functional analyses indicate distinct roles of Notch receptors in different trophoblast subtypes. Altered effects of Notch signalling have been detected in choriocarcinoma cells, consistent with its role in cancer development and progression. Moreover, deregulation of Notch signalling components were observed in pregnancy disorders such as preeclampsia and fetal growth restriction. In summary, Notch plays fundamental roles in different developmental processes of the placenta. Abnormal signalling through this pathway could contribute to the pathogenesis of gestational diseases with aberrant placentation and trophoblast function.

  19. Polyaromatic compounds alter placental protein synthesis in pregnant rats

    SciTech Connect

    Shiverick, K.T.; Ogilvie, S.; Medrano, T. )

    1991-03-15

    The administration of the polyaromatic compounds {beta}-naphthoflavone ({beta}NF) and 3-methylcholanthrene (3MC) to pregnant rats during mid-gestation has been shown to produce marked feto-placental growth retardation. This study examined secretory protein synthesis in placental tissue from rats following administration of {beta}NF on gestation days (gd) 11-14 or 3MC on gd 12-14. Explants of placental basal zone tissue were cultured for 24 hours in serum-free medium in the presence of ({sup 3}H)leucine. Secreted proteins were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis followed by either fluorography or immunostaining. Total incorporation of ({sup 3}H)leucine into secreted proteins was not altered in BZ explants from {beta}NF or 3MC-treated animals. However a selective decrease was observed in ({sup 3}H)leucine incorporation into a major complex of proteins with apparent molecular weight of 25-30,000 and isoelectric point between 5.3 to 5.7. This group of proteins has been further identified as being related to rat pituitary growth hormone (GH) using N-terminal amino acid microsequencing of individual spots from 2-D SDS-PA gels. This is the first report that synthesis of GH-related proteins by rat placenta is decreased following {beta}NF and 3MC administration, a change which may underlie the feto-placental growth retardation associated with these polyaromatic compounds.

  20. Maternal obesity is associated with a lipotoxic placental environment

    USDA-ARS?s Scientific Manuscript database

    Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta ...

  1. MicroRNAs in placental health and disease

    PubMed Central

    Mouillet, Jean-Francois; Ouyang, Yingshi; Coyne, Carolyn; Sadovsky, Yoel

    2015-01-01

    MicroRNAs (miRNAs) constitute a large family of small non-coding RNAs encoded by the genomes of most organisms. They regulate gene expression through post-transcriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade a flurry of studies have shed light on placental miRNAs but have also raised many questions regarding the scope of their biological action. Moreover, the recognition that miRNAs of placental origin are continually released in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. While this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology. PMID:26428496

  2. Development and regulation of placental androstenedione during rat pregnancy

    SciTech Connect

    Jackson, J.A.

    1986-01-01

    The present study determined the ability of the rat placenta to convert (/sup 3/H) pregnenolone (P/sub 5/) substrate to (/sup 3/H)..delta../sup 4/A and (/sup 3/H)T and to the intermediate steroid (/sup 3/H)P/sub 4/ in vitro on days 12 to 18 of gestation. Placental androgen formation increased and the amount of P/sub 4/ formed and not further metabolized to ..delta../sup 4/A decreased during gestation, with the formation of ..delta../sup 4/A 2- to 4-fold greater (p<0.01) than the formation of T. Moreover, the ovarian conversion of (/sup 3/H)..delta../sup 4/A to (/sup 3/H)E/sub 2/ was 2- to 4-fold greater (p<0.05) than the conversion from (/sup 3/H)T. To determine if the ovary, specifically estrogen, regulates placental ..delta../sup 4/A production, rats were ovariectomized (OVX) on day 9 of gestation and given a Silastic capsule containing either E/sub 2/ or vehicle. On day 14 OVX animals had an increased (p <0.01) ability to form placental ..delta../sup 4/A and decreased (p <0.05) ability to form P/sub 4/. The formation of placental ..delta../sup 4/A invitro was correlated with elevated peripheral serum ..delta../sup 4/A concentrations in OVX animals, an effect which was reversed by E/sub 2/.

  3. Intrapartum fever at term: clinical characteristics and placental pathology.

    PubMed

    Kovo, Michal; Schreiber, Letizia; Ben-Haroush, Avi; Shor, Shimrit; Golan, Abraham; Bar, Jacob

    2012-08-01

    To investigate the association between clinical characteristics and placental histopathology in women with intrapartum fever (IPF) at term. Maternal characteristics, intrapartum parameters, neonatal outcome and placental pathology were compared between 120 patients with IPF (≥ 380C) and a control group matched for mode of delivery. Placental lesions were classified as consistent with maternal circulation abnormalities or fetal thrombo-occlusive disease or inflammatory responses of maternal (MIR) or fetal (FIR) origin. Compared to controls the study group was characterized by significantly higher rates of nulliparity, extra-amniotic balloon induction of labor, and epidural anesthesia, higher gestational age, higher white blood cell count, and more vaginal examinations. On multivariate logistic regression analysis, multiple vaginal examinations were independently associated with IPF. MIR was detected in 71% of the study group compared to 21% of controls (p < 0.001), and FIR, in 32.5% and 7.5%, respectively (p < 0.001). IPF was independently associated with inflammation of maternal origin (adjusted odds ratio (OR) 8.0, 95% CI 4.2-15.2, p < 0.001) and fetal origin (adjusted OR 5.2, 95% CI 2.07-13.4, p < 0.001). Neonatal outcome was similar in the two groups. Multiple vaginal examinations are a significant risk factor for the development of IPF. IPF at term is independently associated with placental inflammatory lesions.

  4. Placental malaria, anaemia and low birthweight in Yemen.

    PubMed

    Albiti, Anisa H; Adam, Ishag; Ghouth, Abdulla S

    2010-03-01

    A cross-sectional study was conducted during the period of August 2007-April 2008 at Al-Wahda Teaching Hospital in Yemen to investigate prevalence and risk factors for placental malaria and anaemia and their effects on birthweight. Sociodemographic characteristics were gathered, maternal haemoglobin was measured and blood films were examined for malaria. Newborn birthweight was recorded. Out of 900 parturient women, malaria blood films were positive in 32 (3.6%) cases: in six sets of peripheral, placental and cord samples; in 15 placental and cord samples; and in 11 placental samples only. Malaria was not associated with age and parity, but it was significantly associated with history of fever [odds ratio (OR) 8.5, 95% CI 3.7-19, P<0.001], rural residence (OR 2.5, 95% CI 1.1-5.3, P=0.01) and rainy season (OR 5.1, 95% CI 1.7-15.2, P=0.003). Overall, 694 (77.1%) out of these 900 women had anaemia (Hb<11g/dl) and 16 (1.8%) patients had severe anaemia (Hb<7g/dl). Anaemia was not associated with age, parity and malaria. Low birthweight was significantly associated with malaria (OR 5.7, 95% CI 1.7-18.5; P=0.004). Thus, preventive measures (bednets and intermittent preventive treatment) should be employed for pregnant women regardless of their age or parity.

  5. Placental sulphate transport: a review of functional and molecular studies.

    PubMed

    Shennan, D B

    2012-08-01

    Sulphate is required by the feto-placental unit for a number of important conjugation and biosynthetic pathways. Functional studies performed several decades ago established that sulphate transport in human placental microvillus and basal membrane vesicles was mainly via a DIDS-sensitive anion-exchange mechanism. In contrast, no evidence was found for Na⁺-dependent transport. Studies performed using isolated human placental tissue confirmed anion-exchange as the main mechanism. More recently, molecular studies have established the presence of anion-exchange proteins which could play a role in transplacental sulphate movement. However, the presence of transcripts for NaS2 has been reported and has prompted the suggestion that Na⁺-sulphate cotransport may play an important role in maternal-fetal sulphate transport. This article reviews our present knowledge of placental sulphate transport, both functional and molecular, and attempts to form a model based on the available evidence. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Molecular dating and biogeography of the early placental mammal radiation.

    PubMed

    Eizirik, E; Murphy, W J; O'Brien, S J

    2001-01-01

    The timing and phylogenetic hierarchy of early placental mammal divergences was determined based on combined DNA sequence analysis of 18 gene segments (9779 bp) from 64 species. Using rooted and unrooted phylogenies derived from distinct theoretical approaches, strong support for the divergence of four principal clades of eutherian mammals was achieved. Minimum divergence dates of the earliest nodes in the placental mammal phylogeny were estimated with a quartet-based maximum-likelihood method that accommodates rate variation among lineages using conservative fossil calibrations from nine different nodes in the eutherian tree. These minimum estimates resolve the earliest placental mammal divergence nodes at periods between 64 and 104 million years ago, in essentially every case predating the Cretaceous-Tertiary (K-T) boundary. The pattern and timing of these divergences allow a geographic interpretation of the primary branching events in eutherian history, likely originating in the southern supercontinent Gondwanaland coincident with its breakup into Africa and South America 95-105 million years ago. We propose an integrated genomic, paleontological, and biogeographic hypothesis to account for these earliest splits on the placental mammal family tree and address current discrepancies between fossil and molecular evidence.

  7. Oxidative stress and maternal obesity: feto-placental unit interaction.

    PubMed

    Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

    2014-06-01

    To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Placental vitamin D receptor (VDR) expression is related to neonatal vitamin D status, placental calcium transfer, and fetal bone length in pregnant adolescents.

    PubMed

    Young, Bridget E; Cooper, Elizabeth M; McIntyre, Allison W; Kent, Tera; Witter, Frank; Harris, Z Leah; O'Brien, Kimberly O

    2014-05-01

    The purpose of the study was to identify determinants of placental vitamin D receptor (VDR) expression and placental calcium (Ca) transfer among pregnant adolescents. Placental tissue was obtained in 94 adolescents (≤18 yr) at term. In 12 of these teens, stable Ca isotopes were given intravenously ((42)Ca) and orally ((44)Ca) early in labor. Placental VDR expression was assessed via Western blot and validated by RT-PCR. Maternal-to-fetal Ca transfer was calculated as the enrichment in cord blood at delivery relative to maternal serum enrichment 2 h postdosing. Isotopic study outcomes were examined in relation to fetal long bone length, placental VDR, serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and parathyroid hormone (PTH) in maternal circulation and cord blood at delivery. Placental VDR expression was inversely associated with neonatal 25(OH)D (P=0.012) and positively with neonatal 1,25(OH)2D (P=0.006). Placental VDR was a positive predictor of fetal femur length Z score (P=0.018; R(2)=0.06) and was positively correlated with maternal-to-fetal transfer of intravenous (42)Ca (P=0.004; R(2)=0.62). The fetus may regulate placental VDR expression given the significant associations with neonatal vitamin D metabolites. The association between placental VDR and fetal long bone length may indicate a role for VDR in fetal bone development, potentially by mediating transplacental Ca transfer.

  9. Brain size, life history, and metabolism at the marsupial/placental dichotomy.

    PubMed

    Weisbecker, Vera; Goswami, Anjali

    2010-09-14

    The evolution of mammalian brain size is directly linked with the evolution of the brain's unique structure and performance. Both maternal life history investment traits and basal metabolic rate (BMR) correlate with relative brain size, but current hypotheses regarding the details of these relationships are based largely on placental mammals. Using encephalization quotients, partial correlation analyses, and bivariate regressions relating brain size to maternal investment times and BMR, we provide a direct quantitative comparison of brain size evolution in marsupials and placentals, whose reproduction and metabolism differ extensively. Our results show that the misconception that marsupials are systematically smaller-brained than placentals is driven by the inclusion of one large-brained placental clade, Primates. Marsupial and placental brain size partial correlations differ in that marsupials lack a partial correlation of BMR with brain size. This contradicts hypotheses stating that the maintenance of relatively larger brains requires higher BMRs. We suggest that a positive BMR-brain size correlation is a placental trait related to the intimate physiological contact between mother and offspring during gestation. Marsupials instead achieve brain sizes comparable to placentals through extended lactation. Comparison with avian brain evolution suggests that placental brain size should be constrained due to placentals' relative precociality, as has been hypothesized for precocial bird hatchlings. We propose that placentals circumvent this constraint because of their focus on gestation, as opposed to the marsupial emphasis on lactation. Marsupials represent a less constrained condition, demonstrating that hypotheses regarding placental brain size evolution cannot be generalized to all mammals.

  10. Placenta with Old, Diffuse Infarction that Was Difficult to Differentiate from a Placental Tumor.

    PubMed

    Miyake, Hidehiko; Miyazaki-Igarashi, Miwa; Suzuki, Shunji

    2015-01-01

    Placental lesions, including placental infarction, are associated with fetal and neonatal mortality and morbidity. We present a case of fetal growth restriction associated with an old, diffuse placental infarction. Because the placenta had only a single viable cotyledon, the others being atrophic, the lesion appeared to be a placental tumor on prenatal ultrasonography. The patient did not have pregnancy-induced hypertension. At 31 weeks of gestation, a cesarean delivery was performed because of fetal growth arrest and breech presentation. A small-for-gestational age infant was delivered with Apgar scores of 8 at both 1 and 5 minutes, and the infant had cleft palate and cleft lips. Pathological examination of the placenta revealed an old, diffuse infarction without neoplastic change. In cases in which a placental tumor causing fetal growth restriction is strongly suspected, diffuse placental infarction should be considered as part of the differential diagnosis, because placental tumors are associated with poor maternal prognosis.

  11. Evidence for altered placental blood flow and vascularity in compromised pregnancies

    PubMed Central

    Reynolds, Lawrence P; Caton, Joel S; Redmer, Dale A; Grazul-Bilska, Anna T; Vonnahme, Kimberly A; Borowicz, Pawel P; Luther, Justin S; Wallace, Jacqueline M; Wu, Guoyao; Spencer, Thomas E

    2006-01-01

    The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can ‘rescue’ fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies. PMID:16469783

  12. Placental fetal stem segmentation in a sequence of histology images

    NASA Astrophysics Data System (ADS)

    Athavale, Prashant; Vese, Luminita A.

    2012-02-01

    Recent research in perinatal pathology argues that analyzing properties of the placenta may reveal important information on how certain diseases progress. One important property is the structure of the placental fetal stems. Analysis of the fetal stems in a placenta could be useful in the study and diagnosis of some diseases like autism. To study the fetal stem structure effectively, we need to automatically and accurately track fetal stems through a sequence of digitized hematoxylin and eosin (H&E) stained histology slides. There are many problems in successfully achieving this goal. A few of the problems are: large size of images, misalignment of the consecutive H&E slides, unpredictable inaccuracies of manual tracing, very complicated texture patterns of various tissue types without clear characteristics, just to name a few. In this paper we propose a novel algorithm to achieve automatic tracing of the fetal stem in a sequence of H&E images, based on an inaccurate manual segmentation of a fetal stem in one of the images. This algorithm combines global affine registration, local non-affine registration and a novel 'dynamic' version of the active contours model without edges. We first use global affine image registration of all the images based on displacement, scaling and rotation. This gives us approximate location of the corresponding fetal stem in the image that needs to be traced. We then use the affine registration algorithm "locally" near this location. At this point, we use a fast non-affine registration based on L2-similarity measure and diffusion regularization to get a better location of the fetal stem. Finally, we have to take into account inaccuracies in the initial tracing. This is achieved through a novel dynamic version of the active contours model without edges where the coefficients of the fitting terms are computed iteratively to ensure that we obtain a unique stem in the segmentation. The segmentation thus obtained can then be used as an

  13. Fetal placental prostaglandin metabolism in the peripartum cow

    SciTech Connect

    Gross, T.S.; Williams, W.F.; Lewis, G.S.

    1986-03-05

    Previous results demonstrate that fetal placental tissue synthesizes prostaglandin E (PGE) prior to parturition. When placental membranes do not separate postpartum, PGE synthesis is maintained, while prostaglandin F (PGF) synthesis predominates when the membranes separate. Concurrent with separation is a decline in fetal placental binucleate cell (BNC) numbers. These data suggest a fetal placental conversion of PGE to PGF. For this experiment, placentomes were collected at ten days prepartum (PRE, n=12) and within 1 hr postpartum. Nine of the postpartum animals had fetal membrane separation within 12 hr postpartum (S) and eight did not exhibit membrane separation (NS). For each placentome, fetal (villi) components were manually isolated and examined for the ability to interconvert /sup 3/H labeled PGE/sub 2/ and PGF/sub 2/. All villi were unable to convert PGE/sub 2/ to PGF/sub 2/ (P > .05). The PRE and NS villi were able to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ also declines (P < .05). These data suggest that peripartum fetal placental tissue might synthesize PGF which is then converted to PGE. It is possible that the BNC are directly converting PGF to PGE or that they are modulating this conversion. Therefore, with a decline in BNC numbers, PGF synthesis would predominate.

  14. Role of placental barrier integrity in infection by Trypanosoma cruzi.

    PubMed

    Díaz-Luján, C; Triquell, M F; Castillo, C; Hardisson, D; Kemmerling, U; Fretes, R E

    2016-12-01

    American trypanosomiasis has long been a neglected disease endemic in LatinAmerica, but congenital transmission has now spread Chagas disease to cause a global health problem. As the early stages of the infection of placental tissue and the vertical transmission by Trypanosoma cruzi are still not well understood, it is important to investigate the relevance of the first structure of the placental barrier in chorionic villi infection by T. cruzi during the initial stage of the infection. Explants of human chorionic villi from healthy pregnant women at term were denuded of their syncytiotrophoblast and co-cultured for 3h, 24h and 96h with 800,000 trypomastigotes (simulating acute infection). T. cruzi infected cells were identified by immunohistochemistry for cytokeratin-7 (+cytotrophoblast) and CD68 (+macrophages), and the infection was quantified. In placental tissue, the parasite load was analyzed by qPCR and microscopy, and the motile trypomastigotes were quantified in culture supernatant. In denuded chorionic villous, the total area occupied by the parasite (451.23μm(2), 1.33%) and parasite load (RQ: 87) was significantly higher (p<0.05) than in the entire villous (control) (5.98μm(2), 0.016%) (RQ:1) and with smaller concentration of nitric oxide. Stromal non-macrophage cells were infected as well as cytotrophoblasts and some macrophages, but with significant differences being observed. The parasite quantity in the culture supernatant was significantly higher (p<0.05) in denuded culture explants from 96h of culture. Although the human complete chorionic villi limited the infection, the detachment of the first structure of the placenta barrier (syncytiotrophoblast) increased both the infection of the villous stroma and the living trypomastigotes in the culture supernatant. Therefore structural and functional alterations to chorionic villi placental barrier reduce placental defenses and may contribute to the vertical transmission of Chagas.

  15. Placental Dysferlin Expression is Reduced in Severe Preeclampsia

    PubMed Central

    Lang, Christopher T.; Markham, Kara B.; Behrendt, Nicholas J.; Suarez, Adrian A.; Samuels, Philip; Vandre, Dale D.; Robinson, John M.; Ackerman, William E.

    2009-01-01

    Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE (n = 10) and normotensive controls (n = 10). DYSF and MYOF expression were examined using quantitative real-time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level (p = 0.03) and 38% lower at the protein level (p = 0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villli were observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE. PMID:19545895

  16. The impact of ionizing radiation on placental trophoblasts

    PubMed Central

    Kanter, D.J.; O'Brien, M.B.; Shi, X.-H.; Chu, T.; Mishima, T.; Beriwal, S.; Epperly, M.W.; Wipf, P.; Greenberger, J.S.; Sadovsky, Y.

    2014-01-01

    Introduction Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. Methods Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. Results We found that survival of in vitro–irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. Discussion and conclusion While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation. PMID:24418702

  17. The association between placental histopathology and autism spectrum disorder.

    PubMed

    Straughen, Jennifer K; Misra, Dawn P; Divine, George; Shah, Ruchit; Perez, Gabriela; VanHorn, Samantha; Onbreyt, Victoria; Dygulska, Beata; Schmitt, Rebecca; Lederman, Sanford; Narula, Pramod; Salafia, Carolyn M

    2017-09-01

    Research suggests that autism spectrum disorder (ASD) has its origins in utero. This study examines the association between evidence of placental histopathology and ASD. Administrative claims data and medical records data were used to identify ASD cases (N = 55) and matched controls (N = 199) born at New York Methodist Hospital between 2007 and 2014 and subsequently seen in affiliated pediatrics clinics. Placentas from all births during this time period were reviewed as part of routine care. Data were analyzed using conditional logistic regression to account for the matched (gender, gestational age, and birth weight) design. Acute placental inflammation, regardless of type was associated with an increased risk of ASD (odds ratio [OR] = 3.14, 95% CI = 1.39, 6.95). Chronic uteroplacental vasculitis (OR = 7.13; 95% CI = 1.17, 43.38), the fetal inflammatory response in the chorionic plate vessels (OR = 5.12; 95% CI = 2.02, 12.96), and maternal vascular malperfusion pathology (OR = 12.29; 95% CI = 1.37, 110.69) were associated with an increased risk of ASD. Placental villous edema was associated with a decreased risk of ASD (OR = 0.05; 95% CI = 0.0005, 0.42). In subanalyses among male placentas acute inflammation overall, fetal inflammatory response in the chorionic plate vessels, and maternal vascular malperfusion pathology remained significantly associated with an increased risk of ASD whereas placental villous edema remained associated with a decreased risk of ASD. Histologic evidence of placental inflammation and maternal vascular malperfusion pathology are associated with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Chorioallantoic placentation in Galea spixii (Rodentia, Caviomorpha, Caviidae)

    PubMed Central

    Oliveira, Moacir F; Mess, Andrea; Ambrósio, Carlos E; Dantas, Carlos AG; Favaron, Phelipe O; Miglino, Maria A

    2008-01-01

    Background Placentas of guinea pig-related rodents are appropriate animal models for human placentation because of their striking similarities to those of humans. To optimize the pool of potential models in this context, it is essential to identify the occurrence of characters in close relatives. Methods In this study we first analyzed chorioallantoic placentation in the prea, Galea spixii, as one of the guinea pig's closest relatives. Material was collected from a breeding group at the University of Mossoró, Brazil, including 18 individuals covering an ontogenetic sequence from initial pregnancy to term. Placentas were investigated by means of histology, electron microscopy, immunohistochemistry (vimentin, α-smooth muscle actin, cytokeration) and proliferation activity (PCNA). Results Placentation in Galea is primarily characterized by an apparent regionalization into labyrinth, trophospongium and subplacenta. It also has associated growing processes with clusters of proliferating trophoblast cells at the placental margin, internally directed projections and a second centre of proliferation in the labyrinth. Finally, the subplacenta, which is temporarily supplied in parallel by the maternal and fetal blood systems, served as the center of origin for trophoblast invasion. Conclusion Placentation in Galea reveals major parallels to the guinea pig and other caviomorphs with respect to the regionalization of the placenta, the associated growing processes, as well as trophoblast invasion. A principal difference compared to the guinea pig occurred in the blood supply of the subplacenta. Characteristics of the invasion and expanding processes indicate that Galea may serve as an additional animal model that is much smaller than the guinea pig and where the subplacenta partly has access to both maternal and fetal blood systems. PMID:18771596

  19. Assessment of the developmental toxicity and placental transfer of 1,2-diethylbenzene in rats.

    PubMed

    Saillenfait, A M; Payan, J P; Langonné, I; Gallissot, F; Sabaté, J P; Beydon, D; Fabry, J P

    1999-11-01

    Sprague-Dawley rats were administered 1,2-diethylbenzene (1,2-DEB) by gavage on gestational days (GD) 6 through 20 at dose levels of 0 (corn oil), 5, 15, 25 or 35 mg/kg. The dams were euthanized on GD21 and the offspring were weighed and examined for external, visceral and skeletal alterations. Maternal toxicity, indicated by significant decreases in body weight gain and food consumption, was observed at doses of 15 mg/kg and above. Developmental toxicity, expressed as significantly reduced foetal body weights, was seen at doses of 15 mg/kg and higher. There was no evidence of embryolethal or teratogenic effects at any dose tested. The placental transfer of 1,2-DEB was examined after a single oral dose of 25 mg [14C]1,2-DEB/kg on GD18. Maternal and foetal tissues were collected at intervals from 1 to 48 hours. Placental and foetal tissues accounted for less than 0.35% of the administered dose. Levels of radiocarbon in foetuses were lower than those in maternal plasma and placenta at all time points. Analysis performed at 1, 2 and 4 hours indicated that ethyl acetate extractable (acidic) metabolites were predominant in the maternal plasma while n-hexane extractable (neutral) compounds represented the major part of radioactivity in the placenta and foetus. In conclusion, this study demonstrated that 1,2-DEB causes mild foetotoxicity at maternal toxic doses and that the exposure of the developing rat foetus to 1,2-DEB and/or metabolites after maternal administration of 1,2-DEB in late gestation is small.

  20. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation.

    PubMed

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S

    2014-01-01

    The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.

  1. Placental development during early pregnancy in sheep: effects of embryo origin on fetal and placental growth and global methylation.

    PubMed

    Grazul-Bilska, Anna T; Johnson, Mary Lynn; Borowicz, Pawel P; Baranko, Loren; Redmer, Dale A; Reynolds, Lawrence P

    2013-01-01

    The origin of embryos including those created through assisted reproductive technologies might have profound effects on placental and fetal development, possibly leading to compromised pregnancies associated with poor placental development. To determine the effects of embryo origin on fetal size, and maternal and fetal placental cellular proliferation and global methylation, pregnancies were achieved through natural mating (NAT), or transfer of embryos generated through in vivo (NAT-ET), IVF, or in vitro activation (IVA). On Day 22 of pregnancy, fetuses were measured and placental tissues were collected to immunologically detect Ki67 (a marker of proliferating cells) and 5-methyl cytosine followed by image analysis, and determine mRNA expression for three DNA methyltransferases. Fetal length and labeling index (proportion of proliferating cells) in maternal caruncles (maternal placenta) and fetal membranes (fetal placenta) were less (P < 0.001) in NAT-ET, IVF, and IVA than in NAT. In fetal membranes, expression of 5-methyl cytosine was greater (P < 0.02) in IVF and IVA than in NAT. In maternal caruncles, mRNA expression for DNMT1 was greater (P < 0.01) in IVA compared with the other groups, but DNMT3A expression was less (P < 0.04) in NAT-ET and IVA than in NAT. In fetal membranes, expression of mRNA for DNMT3A was greater (P < 0.01) in IVA compared with the other groups, and was similar in NAT, NAT-ET, and IVF groups. Thus, embryo origin might have specific effects on growth and function of ovine uteroplacental and fetal tissues through regulation of tissue growth, DNA methylation, and likely other mechanisms. These data provide a foundation for determining expression of specific factors regulating placental and fetal tissue growth and function in normal and compromised pregnancies, including those achieved with assisted reproductive technologies.

  2. Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

    PubMed

    Guimarães, Camila S O; Gomes, Bruno B F; Oliveira, Rafael A; Yamamoto, Leandro R; Rocha, Laura P; Glória, Maria A; Machado, Juliana R; Câmara, Niels O S; Reis, Marlene A; Corrêa, Rosana R M

    2016-01-01

    To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

  3. The effects of Carthamus tinctorius L. on placental histomorphology and survival of the neonates in mice

    PubMed Central

    Louei Monfared, Ali; Salati, Amir Parviz

    2012-01-01

    Objective: Carthamus tinctorius L. (Safflower) is a member of the asteraceae family which is used as a food additive but also has medicinal applications. This study investigated its effects on placental histomorphology and survival of mice neonates. Materials and Methods: Eighty Balb/C pregnant mice were randomly distributed into one control and three experimental groups (n=20). The control group received only distilled water, whereas experimental groups were administered intraperitoneally C. tinctorius extract at doses of 0.7, 1.4, and 2.8 mg/kg during the organogenesis period (6th to 16th day of gestation). On the 17th day of gestation, half of the animals were euthanized; their fetuses and placentas were removed and histomorphological study was performed. In the rest of the animals after parturition, the number of neonates was counted. Survival rates were periodically calculated for neonates within days 5, 15, 25, and 42 after birth. The results were evaluated by one-way ANOVA. Results: The results showed that treatment with 1.4 and 2.8 mg/kg C. tinctorius extract caused reduction in the trophoblastic giant cells ratio and increasing in the proportion of labyrinthine interhemal membrane (LIM). Moreover, the size of the labyrinthine zone per whole placenta, weight, diameter, and thickness of the placenta in the mice administered with 1.4 and 2.8 mg/kg C. tinctorius extract became lower than those of controls (p<0.05). In addition, in the treated mice with 1.4 and 2.8 mg/kg C. tinctorius extract, the number of neonate was drastically decreased on days 5, 15, 25, and 42 after birth. Conclusion: It is concluded that treatment with C. tinctorius extract in doses of 1.4 and 2.8 mg/kg induces toxic changes in the placental structure so caution should be paid to popular consumption of this plant both as an alternative medicine and as a food additive. PMID:25050244

  4. Infant sex-specific placental cadmium and DNA methylation associations

    PubMed Central

    Mohanty, April F.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Afsharinejad, Zahra; Burbacher, Thomas M.; Siscovick, David S.; Williams, Michelle A.; Enquobahrie, Daniel A.

    2015-01-01

    Background Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these findings

  5. Brain size, life history, and metabolism at the marsupial/placental dichotomy

    PubMed Central

    Weisbecker, Vera; Goswami, Anjali

    2010-01-01

    The evolution of mammalian brain size is directly linked with the evolution of the brain's unique structure and performance. Both maternal life history investment traits and basal metabolic rate (BMR) correlate with relative brain size, but current hypotheses regarding the details of these relationships are based largely on placental mammals. Using encephalization quotients, partial correlation analyses, and bivariate regressions relating brain size to maternal investment times and BMR, we provide a direct quantitative comparison of brain size evolution in marsupials and placentals, whose reproduction and metabolism differ extensively. Our results show that the misconception that marsupials are systematically smaller-brained than placentals is driven by the inclusion of one large-brained placental clade, Primates. Marsupial and placental brain size partial correlations differ in that marsupials lack a partial correlation of BMR with brain size. This contradicts hypotheses stating that the maintenance of relatively larger brains requires higher BMRs. We suggest that a positive BMR–brain size correlation is a placental trait related to the intimate physiological contact between mother and offspring during gestation. Marsupials instead achieve brain sizes comparable to placentals through extended lactation. Comparison with avian brain evolution suggests that placental brain size should be constrained due to placentals’ relative precociality, as has been hypothesized for precocial bird hatchlings. We propose that placentals circumvent this constraint because of their focus on gestation, as opposed to the marsupial emphasis on lactation. Marsupials represent a less constrained condition, demonstrating that hypotheses regarding placental brain size evolution cannot be generalized to all mammals. PMID:20823252

  6. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    PubMed

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  7. Ovine uterine space restriction alters placental transferrin receptor and fetal iron status during late pregnancy

    PubMed Central

    Sun, Mary Y.; Habeck, Jason M.; Meyer, Katie M.; Koch, Jill M.; Ramadoss, Jayanth; Blohowiak, Sharon E.; Magness, Ronald R.; Kling, Pamela J.

    2013-01-01

    Background Fetal growth restriction is reported to be associated with impaired placental iron transport. Transferrin receptor (TfR) is a major placental iron transporter in humans, but is unstudied in sheep. TfR is regulated by both iron and nitric oxide (NO), the molecule produced by endothelial NOS (eNOS). We hypothesized that limited placental development downregulates both placental TfR and eNOS expression, thereby lowering fetal tissue iron. Methods An ovine surgical uterine space restriction (USR) model, combined with multifetal gestation, tested the extremes of uterine and placental adaptation. Blood, tissues, and placentomes from non-space restricted (NSR) singletons were compared to USR fetuses at 120 or 130 days of gestation (GD). Results When expressed proportionate to fetal weight, liver iron content did not differ while renal iron was higher in USR vs. NSR fetuses. Renal TfR protein expression did not differ, but placental TfR expression was lower in USR fetuses at GD130. Placental levels of TfR correlated to eNOS. TfR was localized throughout the placentome, including the hemophagous zone, implicating a role for TfR in ovine placental iron transport. Conclusion In conclusion, fetal iron was regulated in an organ-specific fashion. In USR fetuses, NO-mediated placental adaptations may prevent the normal upregulation of placental TfR at GD130. PMID:23202722

  8. Short Placental Telomere was Associated with Cadmium Pollution in an Electronic Waste Recycling Town in China

    PubMed Central

    Zhang, Qingying; Fan, Xiaojuan; Du, Li; Xu, Xijin; Qiu, Shaoshan; Zhang, Yuling; Wang, Yun; Gu, Jiang

    2013-01-01

    In Guiyu, an electronic waste recycling site near Shantou, Guangdong province, China, primitive ways of e-waste processing have caused severe cadmium and lead pollution to the local residents. However, the possible effects of cadmium or lead pollution to genomic integrity of the local residents have not been investigated. We examined the possible relationship between cadmium and lead concentrations in placenta and placental telomere length in Guiyu and compared the data with that of a non-polluted town. Graphite furnace atomic absorption spectrometry and real-time PCR were used to determine placental cadmium and lead concentrations, and placental telomere length. We found that placental cadmium concentration was negatively correlated with placental telomere length (r = −0.138, p = 0.013). We also found that placental cadmium concentration of 0.0294 µg/g might be a critical point at which attrition of placental telomere commenced. No significant correlation between placental lead concentration and placental telomere length was detected (r = 0.027, p = 0.639). Our data suggest that exposure to cadmium pollution during pregnancy may be a risk factor for shortened placental telomere length that is known to be related to cancer development and aging. Furthermore, grave consequence on the offspring from pregnancies in e-waste polluted area is indicated. PMID:23565277

  9. IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells☆

    PubMed Central

    Ackerman, W.E.; Bulmer, J.N.; Carter, A.M.; Chaillet, J.R.; Chamley, L.; Chen, C.P.; Chuong, E.B.; Coleman, S.J.; Collet, G.P.; Croy, B.A.; de Mestre, A.M.; Dickinson, H.; Ducray, J.; Enders, A.C.; Fogarty, N.M.E.; Gauster, M.; Golos, T.; Haider, S.; Heazell, A.E.; Holland, O.J.; Huppertz, B.; Husebekk, A.; John, R.M.; Johnsen, G.M.; Jones, C.J.P.; Kalionis, B.; König, J.; Lorenzon, A.R.; Moffett, A.; de Mello, J.C. Moreira; Nuzzo, A.M.; Parham, P.; Parolini, O.; Petroff, M.G.; Pidoux, G.; Ramírez-Pinilla, M.P.; Robinson, W.P.; Rolfo, A.; Sadovsky, Y.; Soma, H.; Southcombe, J.H.; Tilburgs, T.; Lash, G.E.

    2014-01-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells. PMID:22154501

  10. Second-Trimester 3-Dimensional Placental Sonography as a Predictor of Small-for-Gestational-Age Birth Weight.

    PubMed

    Quant, Hayley S; Sammel, Mary D; Parry, Samuel; Schwartz, Nadav

    2016-08-01

    We previously reported the association between first-trimester 3-dimensional (3D) placental measurements and small-for-gestational-age (SGA) neonates. In this study, we sought to determine whether second-trimester measurements further contribute to the antenatal detection of SGA and preeclampsia. We prospectively collected 3D sonographic volume sets and uterine artery pulsatility indices of singleton pregnancies at 18 to 24 weeks. Placental volume, placental quotient (placental volume/gestational age), mean placental diameter and chorionic diameter, placental morphologic index (mean placental diameter/placental quotient), placental chorionic index (mean chorionic diameter/placental quotient), and placental growth (volume per week) were assessed and evaluated as predictors of SGA and preeclampsia as a composite and alone. Of 373 pregnancies, the composite outcome occurred in 67 (18.0%): 36 (9.7%) manifested SGA alone; 27 (7.2%) developed preeclampsia alone, and 4 (1.1%) developed both. The placental volume, placental quotient, mean placental diameter, mean chorionic diameter, and volume per week were significantly smaller, whereas the placental morphologic index and chorionic index were significantly larger in pregnancies with the composite outcome (P < .01). Further analyses revealed that the significant associations with placental parameters were limited to the SGA outcome. Each placental measure remained significantly associated with SGA after adjusting for confounders. The mean uterine artery pulsatility index was not associated with either outcome. Placental parameters were moderately predictive of SGA, with adjusted areas under the curve ranging from 0.72 to 0.76. Sensitivity for detection of SGA ranged from 32.5% to 45.0%, with positive predictive values ranging from 17.3% to 22.7%. Second-trimester 3D placental measurements can identify pregnancies at risk of SGA. However, there appears to be no significant improvement compared to those obtained in the first

  11. A differentially expressed proteomic analysis in placental tissues in relation to pungency during the pepper fruit development.

    PubMed

    Lee, Je Min; Kim, Seyoon; Lee, Ji Young; Yoo, Eun Young; Cho, Myeong Cheoul; Cho, Min Rae; Kim, Byung-Dong; Bahk, Young Yil

    2006-10-01

    Using proteomic analysis including 2-DE, image analysis, and protein identification with LC-MS/MS, an investigation aimed at a better understanding of the differentially expressed proteins and/or gene products was carried out with total cell extracts from placental tissues in nonpungent (Capsicum annuum cv. Saeng-Ryeog #213) and pungent peppers (C. annuum cv. Saeng-Ryeog #211). Mobilization of the most abundant proteins, which were on the gels of pH ranges of 4-7, 4.5-5.5, 5.5-6.7, and 6-9, and showed very similar profiles in the two tissues, revealing approximately 2600 protein spots consisting of 1200 on pH 4-7, 600 on 4.5-5.5, 550 on 5.5-6.7, 250 on 6-9. Of these, 37 protein spots, which appeared in only pungent tissues but not in nonpungent tissues or markedly increased in their staining intensities on the gels from pungent tissue, were selected, excised, in-gel trypsin digested, and analyzed by LC-ESI-MS/MS. Peptide MS/MS data were searched against publicly available protein and EST databases, and 22 proteins were identified. Based on this result, we tested and compared the differential expression during fruit development on the 2-DE gels with total cell extracts from placental tissues of pungent and nonpungent peppers at an interval of 10 days from 10 to 40 days after flowering. In addition, this differential protein expression was further confirmed for some subsets of candidates by Northern-blot analysis with RNA samples from placental tissues harvested from each pepper fruit at the same sampling intervals. In this study, the physiological implications, revealed from the experimental data in the levels of proteome and transcripts, are discussed in the context of a complex biosynthesis network of capsaicinoids in pepper cells responsive to pungency.

  12. Placental steroids in cattle: hormones, placental growth factors or by-products of trophoblast giant cell differentiation?

    PubMed

    Schuler, G; Greven, H; Kowalewski, M P; Döring, B; Ozalp, G R; Hoffmann, B

    2008-07-01

    The bovine placenta produces large amounts of steroids, mainly estrone (E1) and progesterone (P4). Specific features of bovine placental steroidogenesis are 1) the expression of all enzymes needed for the production of estrogens from cholesterol in the trophoblast 2) an only marginal and temporal contribution to peripheral maternal P4 levels restricted to a period between approx. days 150 - 240 of gestation 3) the predominance of sulfoconjugated over free E1 and 4) a complementary setting of steroidogenic enzymes in the two morphologically discriminable trophoblast cell types, the uninucleated trophoblast cells (UTC) and the trophoblast giant cells (TGC). In cattle so far no definite information is available on the specific biological roles of placental estrogens and P4. However, the detection of estrogen receptors and progesterone receptors in the placentomes suggests a role primarily as local regulators of caruncular growth, differentiation and functions. Inconsistent with a function as a caruncular growth factor is the strong evidence that in cattle placental estrogens enter the maternal compartment almost completely as estrone sulfate (E1S), which is not active at classical nuclear receptors. On the other hand, E1S may be converted locally to free active estrogens via the action of steroid sulfatase (StS), which has been detected in specific parts of the bovine caruncular epithelium. Alternatively or in addition, StS expression in the caruncular epithelium may serve the utilization of sulfated neutral steroid precursors (e.g. pregnenolone sulfate or cholesterol sulfate) supplied with maternal blood, thus providing free substrates for further metabolization in the adjacent trophoblast. The down-regulation of P450scc and P450c17 and the up-regulation of 3beta-HSD and aromatase during the differentiation of TGC from UTC in parallel with the up-regulation of ER beta and estrogen sulfotransferase in maturing TGC suggests a function of placental estrogens primarily

  13. [Symptomatic exaggerated placental site after first trimester abortion].

    PubMed

    López-Carpintero, Nayara; de la Fuente-Valero, Jesús; Salazar-Arquero, Francisco Javier; Casado-Fariñas, Isabel; Hernández-Aguado, Juan José

    2015-04-01

    Exaggerated placental site, a trophoblastic benign lesion, is characterized by an extensive infiltration of the endometrium, myometrium and arterial walls by intermediate trophoblast cells. Trophoblastic benign lesions are often an incidental finding in the anatomopathological study, but may be associated with severe bleeding especially in relation to trauma. Case report: Multigravida 39 years old with excessive uterine bleeding after medical treatment of abortion. Once expelled gestational vesicle is seen sonographically a uterine cavity occupied by a heterogeneous endometrium with maximum anteroposterior diameter of 21 mm, plenty of color map, reaching myometrium. B-HCG serum is 164 mlU/ml. During hysteroscopy a massive bleeding happens and its necesary to use an intrauterine catheter to stop it. Computed tomography angiography shows suggestive findings of uterine vascular malformation. A hysterectomy as a diagnostic and definitive treatment is made and pathology reports an exaggerated placental site.

  14. Parvovirus infection: an immunohistochemical study using fetal and placental tissue.

    PubMed

    Li, Jing Jing; Henwood, Tony; Van Hal, Sebastian; Charlton, Amanda

    2015-01-01

    Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.

  15. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    SciTech Connect

    Russell, J.R.; Stabin, M.G.; Sparks, R.B.

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  16. Placental extracellular vesicles and feto-maternal communication.

    PubMed

    Tong, M; Chamley, L W

    2015-01-29

    The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Placental Extracellular Vesicles and Feto-Maternal Communication

    PubMed Central

    Tong, M.; Chamley, L.W.

    2015-01-01

    The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems. PMID:25635060

  18. Placental Vascular Tree as Biomarker of Autism/ASD Risk

    DTIC Science & Technology

    2011-09-01

    same cohort, one with special education needs (SEN) but not a diagnosis of autism/ASD, and one with no diagnoses related to neurodevelopmental pathology...disk edge - differs significantly between autism/ASD cases and the University of North Carolina Pregnancy, Infection and Nutrition Study (UNC PIN... neurodevelopment in this highly heterogeneous spectrum of autism/ASD. Task: Placental processing: P.I.: Carolyn M Salafia, MD, NYS Institute for Basic

  19. Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

    PubMed Central

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

    2015-01-01

    BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

  20. Clinical Outcome in Singleton and Multiple Pregnancies with Placental Chorangioma

    PubMed Central

    Sirotkina, Meeli; Douroudis, Konstantinos; Papadogiannakis, Nikos; Westgren, Magnus

    2016-01-01

    Introduction Chorangiomas (CAs) are the most common non-trophoblastic tumor-like-lesions of the placenta. Although the clinical significance of small CAs is unknown, the large lesions are often associated with maternal and fetal complications. The aim of our study was to assess the maternal clinical characteristics and neonatal outcome in singleton and multiple pregnancies with placental CA. Materials and Methods Among 15742 selected placentas 170 CAs were diagnosed. Pregnancy and neonatal outcomes were analyzed in singleton (n = 121) and multiple (n = 49) pregnancy groups including 121 and 100 neonates, respectively. Results The frequency of APGAR score <7 at 5 minutes (p = 0,012), abnormal pulsatility index (p = 0,034), and abnormal blood flow class (p = 0,011) were significantly higher in neonates from singleton compared to multiple pregnancies. Significantly smaller CAs in singleton pregnancies were related to small for gestational age neonates (p = 0,00040) and neonates admitted to the neonatal care unit (p = 0,028). In singleton pregnancies, significantly smaller CAs were associated to maternal preeclampsia (p = 0,039) and larger CAs to multiparity (p = 0,005) and smoking (p = 0,001) groups. The frequency of preeclampsia was high in both singleton and multiple pregnancy groups (41,32% vs 26,53%, respectively), however, the difference did not reach the level of statistical significance. Discussion A high incidence of preeclampsia in cohort of placental CA might lead to a possible recognition of CAs as potential morphologic indicator of placental hypoxia. Conclusion A more favorable pregnancy outcome in multiple gestations compared to the singleton gestations with CAs might reflect an adaptive mechanism for increased demand of oxygen and associated placental tissue hypoxia in this group. PMID:27835686

  1. Placental Vascular Tree as Biomarker of Autism/ASD Risk

    DTIC Science & Technology

    2012-09-01

    Risk Longitudinal Investigation (EARLI, high-autism risk) placentas compared 76 unselected National Children’s Study (NCS) placentas . Using methods...unique to our team to quantify vascular network structure, we have demonstrated, in summary, that EARLI placentas as a group show significant placental...vascular points and reduced mean vessel caliber as compared to NCS placentas . In addition, in EARLI placentas as a group, chorionic surface arteries, but

  2. Maternal methadone dose, placental methadone concentrations, and neonatal outcomes.

    PubMed

    de Castro, Ana; Jones, Hendreé E; Johnson, Rolley E; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2011-03-01

    Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. Positive correlations were found between placental methadone and EDDP concentrations (r=0.685), and between methadone concentration and methadone dose at delivery (r=0.542), mean daily dose (r=0.554), mean third-trimester dose (r=0.591), and cumulative daily dose (r=0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r=-0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r=0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r=-0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed.

  3. Effects of moderate drinking during pregnancy on placental gene expression

    PubMed Central

    Rosenberg, Martina J.; Wolff, Christina R.; El-Emawy, Ahmed; Staples, Miranda C.; Perrone-Bizzozero, Nora I.; Savage, Daniel D.

    2013-01-01

    Many children adversely affected by maternal drinking during pregnancy cannot be identified early in life using current diagnostic criteria for fetal alcohol spectrum disorder (FASD). We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy and as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring. Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Ethanol consumption produced a mean maternal daily intermittent peak serum ethanol concentration of 84 mg/dL. Placentas were harvested on gestational day 20 for gene expression studies. Microarray analysis of more than 28,000 genes revealed that the expression of 304 known genes was altered twofold or greater in placenta from ethanol-consuming dams compared with controls. About 76% of these genes were repressed in ethanol-exposed placentas. Gene expression changes involved proteins associated with central nervous system development; organ morphogenesis; immunological responses; endocrine function; ion homeostasis; and skeletal, cardiovascular, and cartilage development. To date, quantitative real-time polymerase chain reaction analysis has confirmed significant alterations in gene expression for 22 genes, including genes encoding for three calcium binding proteins, two matrix metalloproteinases, the cannabinoid 1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase 2, 11-β hydroxysteroid dehydrogenase 2, placental growth factor, transforming growth factor alpha, gremlin 1, and epithelial growth factor (EGF)-containing extracellular matrix protein. These results suggest that the expression of a sufficiently large number of placental mRNAs is altered after moderate drinking during pregnancy to warrant more detailed investigation of the placenta as a biomarker system

  4. A microphysiological model of the human placental barrier.

    PubMed

    Blundell, Cassidy; Tess, Emily R; Schanzer, Ariana S R; Coutifaris, Christos; Su, Emily J; Parry, Samuel; Huh, Dongeun

    2016-08-02

    During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers - the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro. Our model is created in a multilayered microfluidic system that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement to replicate the characteristic architecture of the human placental barrier. We have engineered this co-culture model to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembles the syncytiotrophoblast in vivo. Our system also allows the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta. To provide a proof-of-principle for using this microdevice to recapitulate native function of the placental barrier, we demonstrated physiological transport of glucose across the microengineered maternal-fetal interface. Importantly, the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas. Our "placenta-on-a-chip" platform represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta for a wide variety of applications.

  5. Placental maturity, hypertensive disorders of pregnancy and birth weight.

    PubMed

    Ruiz-Quiñonez, Gabriela; Reza-López, Sandra A; Chávez-Corral, Dora Virginia; Sánchez-Ramírez, Blanca; Leal-Berumen, Irene; Levario-Carrillo, Margarita

    2014-05-01

    To compare maturity of placentas from women with hypertensive disorders with those from normotensive pregnancies and to determine the relationship between placental maturity (PM) and the diagnosis of small-for-gestational-age (SGA) in the newborns. We examined placental stained specimens from women with normotensive pregnancies (n = 100), diagnosis of gestational hypertension (n = 38), mild (n = 10), or severe preeclampsia (n = 34) in an optical microscope. Placental Maturity Index (PMI) was calculated as the number of vasculo-syncytial membranes (VSM) in 1 mm(2) divided by VSM thickness (µm). Hypermaturity was defined as >90th percentile of the PMI from placentas of normotensive pregnancies. Newborns were classified as SGA, adequate-for-gestational-age (AGA) or large-for-gestational-age (<10th, 10-90th, and >90th percentile from weight for gestational age reference tables, respectively). PMI in preeclamptic women (taking together mild and severe preeclampsia, PMI = 43.4 ± 1.6) was significantly higher than in normotensive women (PMI = 36 ± 2, p = 0.045). Hypermaturity was more frequent (p < 0.05) in placentas from women with preeclampsia than in those from normotensive women only in preterm pregnancies (<37 weeks), but not in those at term (p = 0.41). The frequency of hypermaturity in placentas from women with gestational hypertension was not statistically different than in normotensive women. Hypermaturity was also more frequent in placentas from SGA (OR = 2.63, p < 0.05) than in AGA newborns. The PMI was increased in preeclampsia, but not in gestational hypertension. Placental hypermaturity was also associated with the diagnosis of SGA in newborns. PM might have a role in the relationship between maternal factors and SGA.

  6. [Oxidative stress level and placental histological changes during preeclampsia].

    PubMed

    Medrano Rodríguez, Juan Carlos; Yahuaca Mendoza, Patricia; Presno Bernal, Manuel; Alvarado Acosta, José Luis

    2008-06-01

    Oxidative stress has been related to several conditions during pregnancy (preeclampsia, abortions and premature rupture of membranes); it causes higher sensitivity of the endothelial blood vessel constriction and aggravates the endothelium dependent vasodilatación. To determine the oxidative stress level and histological changes in preeclamptic women's placenta. Longitudinal and comparative study. There were included 25 patients referred from second level health units (IMSS, ISSSTE and Hospital General de Zacatecas). To evaluate oxidative stress level, a sample of blood and placenta were obtained during delivery and a second sample was taken during mediate puerperium (10 days). In control group, total lipidic peroxide levels in serum were 135.6 +/- 7.3 nmol of MDA/mL of serum, compared with the group of moderate hypertension, which registered 222.0 +/- 35.15 nmol MDA/mL. Total lipidic peroxides in serum during puerperium for control group were 150.4 +/- 30.8 and 183.3 +/- 18.51 nmol MDA/mL for the group of moderate hypertension. Placental lipoperoxidation for control group was 0.40 +/- 0.03 microg MDNg, and of 0.32 +/- 0.03 microg MDN/g for the group of mild hypertension. Patients of moderate hypertension group showed an increase at 34% on placental lipoperoxidation over control group. Placental histological alterations where characterized by vascular remodeling loss, deposits of proteinaceous material and macrophagic process. Total lipidic peroxide levels in serum increases during preeclampsia. Histological changes refer uterus-placental ischemia that, probably, induces the oxidative stress.

  7. William B. Robertson - the pioneer of the placental bed.

    PubMed

    Brosens, Ivo

    2016-12-08

    A fortuitous collaboration between British and Belgian researchers more than 50 years ago led to discovery that major obstetrical disorders, such as preeclampsia and fetal growth restriction, originate from vascular lesions in placental bed, i.e. the myometrial portion of the uterine spiral arteries. William B Robertson, a gregarious pioneering vascular pathologist, played a key role in this seminal discovery that continues to shape obstetrical research to date.

  8. Time- and dose-dependent effects of roundup on human embryonic and placental cells.

    PubMed

    Benachour, N; Sipahutar, H; Moslemi, S; Gasnier, C; Travert, C; Séralini, G E

    2007-07-01

    Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.

  9. Placental sulfatase deficiency: clinical and biochemical study of 16 cases.

    PubMed

    Bedin, M; Alsat, E; Tanguy, G; Cedard, L

    1980-01-01

    Clinical and biochemical data of 16 typical cases of placental sulfatase deficiency have been observed. In vivo loading tests with DHA-S allowed us to make a prenatal diagnosis. In vitro experiments gave confirmation, showing zero or virtually zero placental sulfatase activity towards delta 5P or DHA sulfates Aromatase activities, when tested, were normal or more often less than standard values, the latter showing themselves rather large individual variations. All pregnancies were associated with the delivery of male neonates in good health but 3. The 15 living babies have been developing normally since then. These results, together with those reported in the literature, suggest that placental sulfatase deficiency is under control of an X-linked recessive character, this being supported by the recent observation of such a disorder in two sisters simultaneously pregnant. As to the high frequency problem of cesarian section, pointed out by several authors, we cannot conclude, from our own observations, that the defect has an obvious influence on the good outcome of labor, as 10 out of the 16 women delivered vaginally near term.

  10. Glucose metabolism in pregnant sheep when placental growth is restricted

    SciTech Connect

    Owens, J.A.; Falconer, J.; Robinson, J.S. )

    1989-08-01

    The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-(U-{sup 14}C)- and D-(2-{sup 3}H)glucose and antipyrine into fetuses of six control sheep and six sheep from which endometrial caruncles had been removed before pregnancy (caruncle sheep). In the latter, placental and fetal weights were reduced, as was the concentration of glucose in fetal arterial blood. Fetal glucose turnover in caruncle sheep was only 52-59% of that in controls, largely because of lower umbilical loss of glucose back to the placenta (38-39% of control) and lower fetal glucose utilization (61-74% of control). However, fetal glucose utilization on a weight-specific basis was similar in control and caruncle sheep. Significant endogenous glucose production occurred in control and caruncle fetal sheep. Maternal glucose production and partition of glucose between the gravid uterus and other maternal tissues were similar in control and caruncle sheep. In conclusion, when placental and fetal growth are restricted, fetal glucose utilization is maintained by reduced loss of glucose back to the placenta and mother and by maintaining endogenous glucose production.

  11. Prophylaxis of congenital toxoplasmosis. Effects of spiramycin on placental infection.

    PubMed

    Couvreur, J; Desmonts, G; Thulliez, P

    1988-07-01

    The results of parasitological investigation of the placenta for toxoplasma in 223 cases with documented congenital toxoplasmosis were analysed according to whether the mother had been treated, or not, with spiramycin during pregnancy. The investigation was negative in 10-11% of the cases when the mother had not been treated or had been inadequately treated; in 25% of the cases with a treatment of 3 g spiramycin day; and in 50% with spiramycin plus the combination of pyrimethamine with sulphonamide. This series is compared with a previous group of 321 women whose placental investigation was negative in 50% of untreated cases and 81% of treated women. The treatment categories are not directly comparable, because it is not possible to have a randomly assigned 'no treatment' group, for ethical reasons. Correlation between spiramycin treatment and negative results of mouse inoculation of placental material suggests that spiramycin might decrease the risk of materno-fetal transmission of toxoplasma by reducing the severity and duration of toxoplasmic placentitis. Current use of spiramycin in infected pregnant women is recommended because of its activity and lack of side effects. The dosage must not be lower than 3 g/day. Additional pyrimethamine plus sulphonamide should be restricted to selected cases with fetal abnormality diagnosed during pregnancy. Some data on pharmacology of spiramycin in mothers, placentas and fetuses are reviewed. They suggest that monitoring of maternal serum antibody titres for a dosage more adapted to individual cases may be desirable.

  12. Good practices in collecting umbilical cord and placental blood 1

    PubMed Central

    Lopes, Lauren Auer; Bernardino, Elizabeth; Crozeta, Karla; Guimarães, Paulo Ricardo Bittencourt

    2016-01-01

    Abstract Objective: to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. Method: this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1) verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2) definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r) and R(r). Results: while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. Conclusion: the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality. PMID:27556876

  13. Placental Microbiome and Its Role in Preterm Birth

    PubMed Central

    Cao, Bin; Stout, Molly J.; Lee, Iris; Mysorekar, Indira U.

    2015-01-01

    Despite the well-known fact that the placenta has long-term effects on maternal and fetal health, the placenta remains a poorly understood and understudied organ. Not only is the placenta a site of exchange of nutrients and blood and gases between the fetal and maternal systems, but it also performs critical metabolic functions for supporting fetal development and maintaining maternal-fetal tolerance. It is also abundantly clear that impairment of placental function leads to severe pregnancy complications, including preterm birth (PTB), a significant cause of perinatal mortality and morbidity worldwide. Understanding the causes of PTB and other adverse outcomes is clearly essential for the development of effective methods of prevention and treatment. We focus our review of one major known cause of PTB, namely, infection. We also introduce a new and somewhat unexpected factor(s) that may well affect PTB and every aspect of placental biology and function: the placental microbiome. We discuss the implications of the placenta housing a microbial biomass for PTB and the effect of maternal microbiomes at various niches for fetal colonization and health outcomes. We suggest that the placenta is an integral part of the pipeline for microbe-powered driver of fetal destiny. PMID:25635174

  14. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    PubMed

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Identification of Novel Placentally Expressed Aspartic Proteinase in Humans

    PubMed Central

    Majewska, Marta; Lipka, Aleksandra; Panasiewicz, Grzegorz; Gowkielewicz, Marek; Jozwik, Marcin; Majewski, Mariusz Krzysztof; Szafranska, Bozena

    2017-01-01

    This study presents pioneering data concerning the human pregnancy-associated glycoprotein-Like family, identified in the genome, of the term placental transcriptome and proteome. RNA-seq allowed the identification of 1364 bp hPAG-L/pep cDNA with at least 56.5% homology with other aspartic proteinases (APs). In silico analyses revealed 388 amino acids (aa) of full-length hPAG-L polypeptide precursor, with 15 aa-signal peptide, 47 aa-blocking peptide and 326 aa-mature protein, and two Asp residues (D), specific for a catalytic cleft of the APs (VVFDTGSSNLWV91-102 and AIVDTGTSLLTG274-285). Capillary sequencing identified 9330 bp of the hPAG-L gene (Gen Bank Acc. No. KX533473), composed of nine exons and eight introns. Heterologous Western blotting revealed the presence of one dominant 60 kDa isoform of the hPAG-L amongst cellular placental proteins. Detection with anti-pPAG-P and anti-Rec pPAG2 polyclonals allowed identification of the hPAG-L proteins located within regions of chorionic villi, especially within the syncytiotrophoblast of term singleton placentas. Our novel data extend the present knowledge about the human genome, as well as placental transcriptome and proteome during term pregnancy. Presumably, this may contribute to establishing a new diagnostic tool for examination of some disturbances during human pregnancy, as well as growing interest from both scientific and clinical perspectives. PMID:28594357

  16. Geomolecular Dating and the Origin of Placental Mammals.

    PubMed

    Phillips, Matthew J

    2016-05-01

    In modern evolutionary divergence analysis the role of geological information extends beyond providing a timescale, to informing molecular rate variation across the tree. Here I consider the implications of this development. I use fossil calibrations to test the accuracy of models of molecular rate evolution for placental mammals, and reveal substantial misspecification associated with life history rate correlates. Adding further calibrations to reduce dating errors at specific nodes unfortunately tends to transfer underlying rate errors to adjacent branches. Thus, tight calibration across the tree is vital to buffer against rate model errors. I argue that this must include allowing maximum bounds to be tight when good fossil records permit, otherwise divergences deep in the tree will tend to be inflated by the interaction of rate errors and asymmetric confidence in minimum and maximum bounds. In the case of placental mammals I sought to reduce the potential for transferring calibration and rate model errors across the tree by focusing on well-supported calibrations with appropriately conservative maximum bounds. The resulting divergence estimates are younger than others published recently, and provide the long-anticipated molecular signature for the placental mammal radiation observed in the fossil record near the 66 Ma Cretaceous-Paleogene extinction event. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Placental specializations of the mountain spiny lizard Sceloporus jarrovi.

    PubMed

    Blackburn, Daniel G; Gavelis, Gregory S; Anderson, Kristie E; Johnson, Amy R; Dunlap, Kent D

    2010-10-01

    The lizard Sceloporus jarrovi (Phrynosomatidae) is one of the most widely studied viviparous reptiles of North America. Past research has assumed that placentation in this species is relatively simple and functions mainly in gas exchange. Our examination of the late stage placenta via transmission electron microscopy reveals that S. jarrovi has a unique combination of placental characteristics, with unusual specializations for secretion and absorption. In the chorioallantoic placenta, chorionic and uterine tissues are directly apposed through eggshell loss, and their epithelia are greatly attenuated, enhancing gas exchange; this placenta shows evidence of both nutrient transfer and endocrine function. Contrary to past inferences, a yolk sac placenta forms from the avascular omphalopleure and persists through the end of gestation. The uterine epithelium is enlarged and secretory, and the fetal omphalopleure shows branching absorptive channels and other specializations for uptake. Elsewhere, the omphalopleure develops elongated folds that protrude into a coagulum of degenerating shell membrane and other organic material. Uterine tissue in this region shows specializations for absorption. Placental features in S. jarrovi have unexpected functional implications, and challenge assumptions that specializations for nutrient transfer are confined to matrotrophic species. © 2010 Wiley-Liss, Inc.

  18. Hemodynamic aspects of normal human feto-placental (umbilical) circulation.

    PubMed

    Acharya, Ganesh; Sonesson, Sven-Erik; Flo, Kari; Räsänen, Juha; Odibo, Anthony

    2016-06-01

    Understanding the changes in normal circulatory dynamics that occur during the course of pregnancy is essential for improving our knowledge of pathophysiological mechanisms associated with feto-placental diseases. The umbilical circulation is the lifeline of the fetus, and it is accessible for noninvasive assessment. However, not all hemodynamic parameters can be reliably measured in utero using currently available technology. Experimental animal studies have been crucial in validating major concepts related to feto-placental circulatory physiology, but caution is required in directly translating the findings of such studies into humans due to species differences. Furthermore, it is important to establish normal reference ranges and take into account gestational age associated changes while interpreting the results of clinical investigation. Therefore, it is necessary to critically evaluate, synthesize and summarize the knowledge available from the studies performed on human pregnancies to be able to appropriately apply them in clinical practice. This narrative review is an attempt to present contemporary concepts on hemodynamics of feto-placental circulation based on human studies. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  19. Placental mTOR links maternal nutrient availability to fetal growth.

    PubMed

    Roos, Sara; Powell, Theresa L; Jansson, Thomas

    2009-02-01

    The mTOR (mammalian target of rapamycin) signalling pathway functions as a nutrient sensor, both in individual cells and, more globally, in organs such as the fat body in Drosophila and the hypothalamus in the rat. The activity of placental amino acid transporters is decreased in IUGR (intrauterine growth restriction), and recent experimental evidence suggests that these changes contribute directly to the restricted fetal growth. We have shown that mTOR regulates the activity of the placental L-type amino acid transporter system and that placental mTOR activity is decreased in IUGR. The present review summarizes the emerging evidence implicating placental mTOR signalling as a key mechanism linking maternal nutrient and growth factor concentrations to amino acid transport in the human placenta. Since fetal growth is critically dependent on placental nutrient transport, placental mTOR signalling plays an important role in the regulation of fetal growth.

  20. Classics revisited. History of reptile placentology: Studiati's early account of placentation in a viviparous lizard.

    PubMed

    Blackburn, Daniel G; Avanzati, Anna Marie; Paulesu, Luana

    2015-11-01

    Although placental diversity in mammals received growing attention in the 1600s through the early 1800s, placentation was not documented in reptiles until the mid-19th century. In his classic 1855 study on a viviparous lizard, Cesare Studiati (University of Pisa) described a structural/functional arrangement of fetal and maternal tissues that meets contemporary criteria for recognition of placentation. Through the fortuitous selection of a highly placentotrophic species, Chalcides chalcides, Studiati recognized the functional role of placental tissues in provision of oxygen as well as nutrients. Although Studiati worked in a pre-evolutionary milieu and without the benefits of histological techniques, his findings revealed that viviparous reptiles could exhibit placental specializations that paralleled those of mammals. Accordingly, his classic paper initiated a highly productive body of research that has continued to the present and highlighted specializations of a species that has figured importantly in placental research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Correlation of ultrasound estimated placental volume and umbilical cord blood volume in term pregnancy

    PubMed Central

    Pannopnut, Papinwit; Kitporntheranunt, Maethaphan; Paritakul, Panwara; Kongsomboon, Kittipong

    2015-01-01

    Objective To investigate the correlation between ultrasound measured placental volume and collected umbilical cord blood (UCB) volume in term pregnancy. Material and Methods An observational cross-sectional study of term singleton pregnant women in the labor ward at Maha Chakri Sirindhorn Medical Center was conducted. Placental thickness, height, and width were measured using two-dimensional (2D) ultrasound and calculated for placental volume using the volumetric mathematic model. After the delivery of the baby, UCB was collected and measured for its volume immediately. Then, birth weight, placental weight, and the actual placental volume were analyzed. The Pearson’s correlation was used to determine the correlation between each two variables. Results A total of 35 pregnant women were eligible for the study. The mean and standard deviation of estimated placental volume and actual placental volume were 534±180 mL and 575±118 mL, respectively. The median UCB volume was 140 mL (range 98–220 mL). The UCB volume did not have a statistically significant correlation with the estimated placental volume (correlation coefficient 0.15; p=0.37). However, the UCB volume was significantly correlated with the actual placental volume (correlation coefficient 0.62; p<0.001) and birth weight (correlation coefficient 0.38; p=0.02). Conclusion The estimated placental volume by 2D ultrasound was not significantly correlated with the UCB volume. Further studies to establish the correlation between the UCB volume and the estimated placental volume using other types of placental imaging may be needed. PMID:26097385

  2. Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers

    PubMed Central

    Brantley, Jonathan N.; Verla, Thomas D.

    2015-01-01

    Significance: Chronic diabetic foot ulcers (DFUs) remain a challenge for physicians to treat. High mortality rates for DFU patients have pointed to the low effectiveness of standard care and lack of quality wound care products. The composition (collagen-rich tissue matrix and endogenous growth factors and cells) and functional properties (anti-inflammatory, anti-bacterial, and angiogenic) of placental membranes are uniquely suited to address the needs of chronic wounds. This led to the commercialization of placental membranes, which are now widely available to physicians as a new advanced wound treatment option. Recent Advances: Progress in tissue processing and preservation methods has facilitated the development of placental products for wounds. Currently, a variety of commercial placental products are available to physicians for the treatment of chronic DFUs and other wounds. This review summarizes the key factors that negatively impact DFU healing (including social factors, such as smoking, vascular deficiencies, hyperglycemia, and other metabolic abnormalities), describes the structure and biology of placental membranes, and overviews commercially available placental products for wounds and data from the most recent DFU clinical trials utilizing commercial placental membranes. Critical Issues: Although the effects of diabetes on wound healing are complex and not fully understood, some of the key factors and pathways that interfere with healing have been identified. However, a multidisciplinary approach for the assessment of patients with chronic DFUs and guidelines for selection of appropriate treatment modalities remain to be implemented. Future Directions: The biological properties of placental membranes show benefits for the treatment of chronic DFUs, but scientific and clinical data for commercially available placental products are limited. Therefore, we need (1) more randomized, controlled clinical trials for commercial placental products; (2) studies

  3. Mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency.

    PubMed

    Novielli, Chiara; Mandò, Chiara; Tabano, Silvia; Anelli, Gaia M; Fontana, Laura; Antonazzo, Patrizio; Miozzo, Monica; Cetin, Irene

    2017-07-01

    Intrauterine growth restriction (IUGR) and preeclampsia (PE) are pregnancy disorders characterized by placental insufficiency with oxygen/nutrient restriction and oxidative stress, all influencing mitochondria functionality and number. Moreover, IUGR and PE fetuses are predisposed to diseases later in life, and this might occur through epigenetic alterations. Here we analyze content and methylation of mitochondrial DNA (mtDNA), for the first time in IUGR and PE singleton fetuses, to identify possible alterations in mtDNA levels and/or epigenetic control of mitochondrial loci relevant to replication (D-loop) and functionality (mt-TF/RNR1: protein synthesis, mt-CO1: respiratory chain complex). We studied 35 term and 8 preterm control, 31 IUGR, 17 PE/IUGR and 17 PE human singleton pregnancies with elective cesarean delivery. Fetal cord blood was collected and evaluated for biochemical parameters. Extracted DNA was subjected to Real-time PCR to assess mtDNA content and analyzed for D-loop, mt-TF/RNR1 and mt-CO1 methylation by bisulfite conversion and pyrosequencing. mtDNA levels were increased in all pathologic groups compared to controls. Mitochondrial loci showed very low methylation levels in all samples; D-loop methylation was further decreased in the most severe cases and associated to umbilical vein pO2. mt-CO1 methylation levels inversely correlated to mtDNA content. Increased mtDNA levels in IUGR, PE/IUGR and PE cord blood may denote a fetal response to placental insufficiency. Hypomethylation of D-loop, mt-TF/RNR1 and mt-CO1 loci confirms their relevance in pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Utero-placental transfer of alternate energy substrates and glucose homeostasis in the newborn pig

    SciTech Connect

    Thulin, A.J.

    1985-01-01

    In the first experiment, three sows in late gestation were infused with (/sup 14/C)..beta..-hydroxybutyrate to evaluate utero-placental transfer of ketones. ..beta..-Hydroxy-butyrate (BOHB) concentrations were low in both the mother and fetus throughout the experiments (0.0189, 0.0197, 0.0054, and 0.0063 mmole/liter blood for UV, UA, FV, and FA, respectively). Radioactive BOHB was detected in fetal blood within two minutes post-injection. Lipid extracts of liver and adipose tissue exhibited the greatest relative incorporation of (/sup 14/C)..beta..-hydroxybutyrate followed by lung and heart tissues (3540, 3674, 1214, and 528 dpm/g wet weight, respectively). In a second study, five gravid gilts during late gestation were used to determine utero-placental transfer of maternal free fatty acids (FFA). Using similar techniques as Exp. 1, injections were given containing (/sup 14/C) linoleic acid and (/sup 3/H) palmitic acid or (/sup 14/C) octanoic acid. In a third experiment, gravid gilts were fed supplemental energy as starch (C), soybean oil (SO) or medium-chain triglycerides (MCT) during late gestation to determine the influence on colostrum composition and neonatal pig glucose homeostasis. Energy content of colostrum was increased (P = 0.05 by feeding SO and MCT. After a 36 h fast, mean piglet glucose concentrations were higher (P < 0.05) for MCT pigs. Glucose and creatinine levels showed quadratic effects, while FFA and blood urea nitrogen (BUN) exhibited cubic patterns during the fasting period. Although creatine levels were similar, BUN concentrations were higher (P < 0.01) for MCT progeny.

  5. Identification of a Novel Member of the Chloride Intracellular Channel Gene Family (CLIC5) That Associates with the Actin Cytoskeleton of Placental Microvilli

    PubMed Central

    Berryman, Mark; Bretscher, Anthony

    2000-01-01

    The chloride intracellular channel (CLIC) gene family has been implicated in chloride ion transport within various subcellular compartments. We report here the molecular, biochemical, and cellular characterization of a new member of this gene family termed CLIC5. CLIC5 was isolated from extracts of placental microvilli as a component of a multimeric complex consisting of several known cytoskeletal proteins, including actin, ezrin, α-actinin, gelsolin, and IQGAP1. We cloned human cDNAs and generated antibodies specific for CLIC5, CLIC1/NCC27, and CLIC4/huH1/p64H1. CLIC5 shares 52–76% overall identity with human CLIC1, CLIC2, CLIC3, and CLIC4. Northern blot analysis showed that CLIC5 has a distinct pattern of expression compared with CLIC1 and CLIC4. Immunoblot analysis of extracts from placental tissues demonstrated that CLIC4 and CLIC5 are enriched in isolated placental microvilli, whereas CLIC1 is not. Moreover, in contrast to CLIC1 and CLIC4, CLIC5 is associated with the detergent-insoluble cytoskeletal fraction of microvilli. Indirect immunofluorescence microscopy revealed that CLIC4 and CLIC5 are concentrated within the apical region of the trophoblast, whereas CLIC1 is distributed throughout the cytoplasm. These studies suggest that CLIC1, CLIC4, and CLIC5 play distinct roles in chloride transport and that CLIC5 interacts with the cortical actin cytoskeleton in polarized epithelial cells. PMID:10793131

  6. Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy.

    PubMed

    Miller, Emily S; Minturn, Lucy; Linn, Rebecca; Weese-Mayer, Debra E; Ernst, Linda M

    2016-01-01

    The American Congress of Obstetricians and Gynecologists places special emphasis on autopsy as one of the most important tests for evaluation of stillbirth. Despite a recommendation of an autopsy, many families will decline the autopsy based on religious/cultural beliefs, fear of additional suffering for the child, or belief that no additional information will be obtained or of value. Further, many obstetric providers express a myriad of barriers limiting their recommendation for a perinatal autopsy despite their understanding of its value. Consequently, perinatal autopsy rates have been declining. Without the information provided by an autopsy, many women are left with unanswered questions regarding cause of death for their fetus and without clear management strategies to reduce the risk of stillbirth in future pregnancies. To avoid this scenario, it is imperative that clinicians are knowledgeable about the benefit of autopsy so they can provide clear information on its diagnostic utility and decrease potential barriers; in so doing the obstetrician can ensure that each family has the necessary information to make an informed decision. We sought to quantify the contribution of placental pathologic examination and autopsy in identifying a cause of stillbirth and to identify how often clinical management is modified due to each result. This is a cohort study of all cases of stillbirth from 2009 through 2013 at a single tertiary care center. Records were reviewed in a stepwise manner: first the clinical history and laboratory results, then the placental pathologic evaluation, and finally the autopsy. At each step, a cause of death and the certainty of that etiology were coded. Clinical changes that would be recommended by information available at each step were also recorded. Among the 144 cases of stillbirth examined, 104 (72%) underwent autopsy and these cases constitute the cohort of study. The clinical and laboratory information alone identified a cause of death

  7. Gestational diabetes is associated with changes in placental microbiota and microbiome.

    PubMed

    Bassols, Judit; Serino, Matteo; Carreras-Badosa, Gemma; Burcelin, Rémy; Blasco-Baque, Vincent; Lopez-Bermejo, Abel; Fernandez-Real, José-Manuel

    2016-12-01

    The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines. Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy. Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P < 0.05). In GDM, lower abundance of placental Acinetobacter associated with a more adverse metabolic (higher O'Sullivan glucose) and inflammatory phenotype (lower blood eosinophil count and lower placental expression of IL10 and TIMP3) (P < 0.05 to P = 0.001). Calcium signaling pathway was increased in GDM placental microbiome. A distinct microbiota profile and microbiome is present in GDM. Acinetobacter has been recently shown to induce IL-10 in mice. GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiota a new target for therapy in GDM.

  8. Provocative ideas on human placental biology: A prerequisite for prevention and treatment of neonatal health challenges.

    PubMed

    Sehgal, Shilpi; Bhatnagar, Shinjini; Pallavi, S K

    2017-05-01

    A 2-day invite-only meeting on generating "Provocative Ideas on human placental research" was organized on 1-2 December 2015 at the Translational Health Science and Technology Institute, Faridabad. This meeting was sponsored by Department of Biotechnology, Ministry of Science and Technology, Govt. of India. The objectives of this meeting were the critical evaluation of placental physiology and its development. Special emphasis was placed on understanding the consequences and implications of placental development in sustenance of pregnancy and in pregnancy-associated complications such as preeclampsia, intrauterine growth restriction, and preterm birth. This meeting brought together experienced as well as novice clinicians and biologists who have a keen interest in the field of placental biology, including development of new technologies and methods for evaluating the role of placenta in predicting pregnancy outcomes. The meeting primarily focused on (i) high-throughput "-omics" approaches, (ii) maternal nutrition and placental function, (iii) placental infection and inflammation, (iv) real-time evaluation of placental development: tools for placental research, and (v) epidemiologic relevance of placental-based research. Unanimous consensus emerged among the participants to carry out additional work focused on these areas. In this article, we summarize the talks and review the published literature on the above-mentioned niches. As a direct outcome of this meeting, a request for applications has been announced by the Department of Biotechnology, Government of India, for pursuing research in this vital but understudied domain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Developmental indices of nutritionally induced placental growth restriction in the adolescent sheep.

    PubMed

    Lea, Richard G; Hannah, Lisa T; Redmer, Dale A; Aitken, Raymond P; Milne, John S; Fowler, Paul A; Murray, Joanne F; Wallace, Jacqueline M

    2005-04-01

    Most intrauterine growth restriction cases are associated with reduced placental growth. Overfeeding adolescent ewes undergoing singleton pregnancies restricts placental growth and reduces lamb birth weight. We used this sheep model of adolescent pregnancy to investigate whether placental growth restriction is associated with altered placental cell proliferation and/or apoptosis at d 81 of pregnancy, equivalent to the apex in placental growth. Adolescent ewes with singleton pregnancies were offered a high or moderate level of a complete diet designed to induce restricted or normal placental size at term, respectively. Bromodeoxyuridine (Brd-U) was administered to H and M ewes 1 h before slaughter. Placental tissues were examined for a) Brd-U (immunohistochemistry) and b) apoptosis regulatory genes by in situ hybridization, Northern analyses (bax, mcl-1), immunohistochemistry, and Western analyses (bax). Quantification was carried out by image analysis. Total placentome weights were equivalent between groups. Brd-U predominantly localized to the trophectoderm and was significantly lower in the H group. Bax and mcl-1 mRNA were localized to the maternal-fetal interface. Bax protein was significantly increased in the H group and predominant in the uninuclear fetal trophectoderm. These observations indicate that reduced placental size at term may be due to reduced placental cell proliferation and possibly increased apoptosis occurring much earlier in gestation.

  10. First trimester placental volume and vascular indices in pregnancies complicated by preeclampsia.

    PubMed

    Plasencia, Walter; González-Dávila, Enrique; González Lorenzo, Alejandra; Armas-González, Marina; Padrón, Erika; González-González, Nieves L

    2015-12-01

    To analyze placental volume and vascularization at first trimester in women with pre-eclampsia, and secondarily, the effect of maternal characteristics on placental development and perinatal outcomes. This was a prospective cohort study including women seen between 11 and 14 weeks of pregnancy. Biophysical and biochemical markers included in the screening program for aneuploidy were recorded. Placental volume and vascularization indices were obtained using three-dimensional power-Doppler imaging and Virtual Organ Computer-aided Analysis (VOCAL) techniques. We compared 84 women with pre-eclampsia versus 904 non-affected. Placental volume and all vascular indices were lower in those with pre-eclampsia. Multivariate analysis showed that parity and maternal weight had a significant effect on placental volume and vascularization indices (p = 0.004 and p = 0.011). In women with pre-eclampsia, multiparity showed a negative effect on placental volume, gestational age, birth weight and Apgar test score. By contrast, in the non-affected group, multiparity had a protective effect. Low maternal weight had a significantly worse effect on placental vascularization and perinatal outcomes in women with pre-eclampsia. Women with pre-eclampsia showed significantly lower placental volume and vascularization indices at first trimester. Multiparity and low maternal weight independently exacerbated the negative effects of pre-eclampsia on placental characteristics and perinatal outcomes. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  11. Maternal and feto-placental phenotypes of early-onset severe preeclampsia.

    PubMed

    Pilliod, Rachel A; Feinberg, Bruce B; Burwick, Richard M

    2016-01-01

    To characterize maternal and feto-placental phenotypes of severe preeclampsia that trigger early-onset delivery. A retrospective cohort review of pregnant women receiving care from 2000 to 2010. Subjects with early-onset severe preeclampsia delivering between 20 and 32 weeks were identified excluding multiple gestations or major anomalies. We defined indications for delivery as maternal (i.e. severe headache or abnormal laboratory parameters), feto-placental (i.e. non-reassuring tracing) or mixed (i.e. both maternal and feto-placental factors). To characterize the groups, demographic, clinical, laboratory, ultrasound and pathology data were abstracted. Statistical analysis was conducted. We identified 164 subjects meeting inclusion criteria. Indications for delivery were maternal (57.3%), feto-placental (29.9%) or mixed (12.8%). Compared to neonates delivered for maternal indications, birthweight was significantly lower among neonates delivered for feto-placental or mixed indications (p < 0.001). While placental findings were largely similar between groups, abnormal cord insertion was more common in subjects delivered for feto-placental factors (p = 0.02). Women delivered for maternal indications had more significant lab abnormalities than women delivered for feto-placental or mixed indications. In attempting to classify early-onset severe preeclampsia by delivery indication, we found patterns to suggest that feto-placental and maternal phenotypes of disease may have distinct pathophysiologic underpinnings.

  12. Review: Exploration of placentation from human beings to ocean-living species.

    PubMed

    Soma, H; Murai, N; Tanaka, K; Oguro, T; Kokuba, H; Yoshihama, I; Fujita, K; Mineo, S; Toda, M; Uchida, S; Mogoe, T

    2013-03-01

    This review covers four topics. 1) Placental pathology in Himalayan mountain people. To determine morphological changes of the placenta at high altitude, pathological examination was made of 1000 Himalayan placentas obtained in Nepal and Tibet and the results compared with Japanese placentas delivered at sea level. Characteristic findings in the placental villi of the Himalayan group included high incidences of villous chorangiosis and chorangioma. These processes were clarified by ultrastructural observation. 2) Placentation in Sirenians. The giant Takikawa sea cow, which lived 5 million years ago, was discovered on Hokkaido, Japan. It was an ancestor of the dugong as well as the manatees. Sirenia, the sea cow group, shares a common ancestor with Proboscidea, the elephants, even though they now inhabit quite different environments. A comparison was made of their zonary endothelial type of placentation. 3) Placentation in sharks and rays. The remarkable placentation of hammerhead sharks and manta rays is described. 4) Placentation in the Antarctic minke whale. Placental tissue samples of this whale were obtained from the Japan Institute of Cetacean Research. In an ultrastructural study of the utero-placental junction, microfilamental processes of the allantochorionic zone and crypt formation were visualized.

  13. Altered feto-placental vascularization, feto-placental malperfusion and fetal growth restriction in mice with Egfl7 loss of function.

    PubMed

    Lacko, Lauretta A; Hurtado, Romulo; Hinds, Samantha; Poulos, Michael G; Butler, Jason M; Stuhlmann, Heidi

    2017-07-01

    EGFL7 is a secreted angiogenic factor produced by embryonic endothelial cells. To understand its role in placental development, we established a novel Egfl7 knockout mouse. The mutant mice have gross defects in chorioallantoic branching morphogenesis and placental vascular patterning. Microangiography and 3D imaging revealed patchy perfusion of Egfl7(-/-) placentas marked by impeded blood conductance through sites of narrowed vessels. Consistent with poor feto-placental perfusion, Egfl7 knockout resulted in reduced placental weight and fetal growth restriction. The placentas also showed abnormal fetal vessel patterning and over 50% reduction in fetal blood space. In vitro, placental endothelial cells were deficient in migration, cord formation and sprouting. Expression of genes involved in branching morphogenesis, Gcm1, Syna and Synb, and in patterning of the extracellular matrix, Mmrn1, were temporally dysregulated in the placentas. Egfl7 knockout did not affect expression of the microRNA embedded within intron 7. Collectively, these data reveal that Egfl7 is crucial for placental vascularization and embryonic growth, and may provide insight into etiological factors underlying placental pathologies associated with intrauterine growth restriction, which is a significant cause of infant morbidity and mortality. © 2017. Published by The Company of Biologists Ltd.

  14. Costs and benefits of polyandry in a placental poeciliid fish Heterandria formosa are in accordance with the parent-offspring conflict theory of placentation.

    PubMed

    Ala-Honkola, O; Friman, E; Lindström, K

    2011-12-01

    In viviparous species, a conflict over maternal resource allocation may arise between mothers and embryos, between siblings, and between maternal and paternal genes within an embryo due to relatedness asymmetries. We performed two experiments to study the effects of polyandry and brood relatedness on offspring growth in a placental fish (Heterandria formosa). Polyandry was beneficial as it increased the probability of pregnancy, possibly to avoid genetic incompatibility. However, females mated to four males produced offspring that had a longer maturation time than those of monandrous females. When within-brood relatedness was manipulated, the size of the newborn offspring decreased with time in low-relatedness treatment, whereas in highly related broods, offspring size was constant. Low within-brood relatedness may lead to less cooperative offspring in terms of resource extraction from the mother, which may lead to impaired development during gestation. Offspring conflict may thus reduce the benefits of polyandry in viviparous species. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  15. Comparative effects of recombinant ovine placental lactogen and bovine growth hormone on galactopoiesis in ewes.

    PubMed

    Min, S H; Mackenzie, D D; McCutcheon, S N; Breier, B H; Gluckman, P D

    1997-04-01

    The effects of recombinant ovine placental lactogen and bovine growth hormone on milk yield, milk composition, and concentrations of blood hormones and metabolites were compared in ewes during an established lactation. Beginning on d 17 of lactation, ewes were treated for 5 d with twice daily subcutaneous injections of ovine placental lactogen (n = 9), bovine growth hormone (n = 10) at a dose of 0.10 mg/d per kg of body weight, or saline (n = 10). Circulating concentrations of ovine placental lactogen were 24.6 +/- 1.6 ng/ml on d 5 for ewes treated with ovine placental lactogen, but concentrations of ovine placental lactogen were undetectable in ewes treated with either saline or bovine growth hormone. Treatment with bovine growth hormone increased circulating concentrations of growth hormone, insulin-like growth factor-I, and nonesterified fatty acids and decreased urea concentrations relative to those in ewes treated with ovine placental lactogen or saline. Compared with saline treatment, no parameters were affected by treatment with ovine placental lactogen. Treatment with bovine growth hormone or ovine placental lactogen treatment had no significant effects on plasma concentrations of insulin, glucose, or creatinine. Treatment with bovine growth hormone, but not ovine placental lactogen, increased yields of milk, fat, and lactose. Weight of the mammary gland was increased by bovine growth hormone, but not by ovine placental lactogen. Despite the fact that ovine placental lactogen is a potent somatogen, it does not appear to exhibit the same galactopoietic activity as bovine growth hormone in lactating ewes.

  16. [Placental villous lesions in HIV-1 infection treated with zidovudine].

    PubMed

    Castejón, Olivar C; López, Angela J; Pérez Ybarra, Luis M; Castejón, Oliver C

    2011-05-01

    HIV-1 reaches the placenta through the maternal-fetal transmission from an infected uterus. This virus has cytolytic capabilities. The placenta in its maturation process has regressive or degenerative changes within certain limits, are considered normal. However, factors such as virus and antiretrovirals, can increase the proportion of these lesions. To evaluate morphological changes in placental villi of pregnant women infected with HIV-1 treated with AZT. descriptive, prospective, comparative, with non-probability sampling of observations in villi as units of analysis of the placentas from the group of patients with HIV-1 infection and zidovudine regimen and of the control group of four placentas from HIV negative patients. Both groups in the last trimester of pregnancy. H-E staining was used in 25 films from five placental regions of the study group and four from the control group, using a protocol of 6 variables identifying syncytial knots, fibrinoid changes, villous edema, stromal fibrosis, calcification and villous immaturity. Observations were analyzed using ANOVA as a 2 x 5 factorial arrangement with 4 replications subsampling and split plot design and Tukey test. Chorionic villi showed percentages of alterations that exceed the normal range. It showed significant differences (p<0.05) between the placentas exposed to HIV-1 and AZT and normal placentas in relation to the percentage of villi affected by 5 variables, except fibrosis. The lesions may be increasing the vertical transmission of HIV-1. We also found evidence that the placenta is not in the best conditions for the transfer of gases, nutrients and metabolites, which could promote a decrease in birth weight and placental weight.

  17. Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

    PubMed Central

    Albergotti, Lori C.; Hamlin, Heather J.; McCoy, Michael W.; Guillette,, Louis J.

    2009-01-01

    Background During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. Methodology/Principal Findings We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68 = 89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. Conclusions/Significance Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental

  18. Maternal Obesity is Associated with a Lipotoxic Placental Environment

    PubMed Central

    Saben, Jessica; Lindsey, Forrest; Zhong, Ying; Thakali, Keshari; Badger, Thomas M.; Andres, Aline; Gomez-Acevedo, Horacio; Shankar, Kartik

    2014-01-01

    Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19–24 kg/m2; n = 12) and obese groups (BMI, 32–43 kg/m2; n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by ≥1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-κB(p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1α protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress. PMID:24484739

  19. Effect of maternal tobacco smoke exposure on the placental transcriptome.

    PubMed

    Bruchova, H; Vasikova, A; Merkerova, M; Milcova, A; Topinka, J; Balascak, I; Pastorkova, A; Sram, R J; Brdicka, R

    2010-03-01

    Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious neonatal health problems and chronic lifelong disabilities for the children (e.g., mental retardation, learning problems). To study the effects of tobacco smoke on the placental transcriptome, we performed gene expression profiling on placentas from women exposed to tobacco smoke in pregnancy (N = 12) and from those without significant exposure (N = 64). Gene expression profiles were determined by Illumina HumanRef-8 v2 Expression BeadChips with 18,216 gene probes. Microarray data were normalized by quantile method and filtered for a detection P-value <0.01. Differential gene expression was determined by moderated t-statistic. A linear model was fitted for each gene given a series of arrays using lmFit function. Multiple testing correction was performed using the Benjamini and Hochberg method. Abundant levels of transcripts were found for genes encoding placental hormones (CSH1, CSHL1), pregnancy-specific proteins (PSG3, PSG4, PAPPA), and hemoglobins (HBB, HBG, HBA). Comparative analysis of smokers vs nonsmokers revealed the differential expression of 241 genes (P < 0.05). In smoker cohort, we detected high up-regulation of xenobiotic genes (CYP1A1, CYP1B1, CYB5A, COX412), collagen genes (e.g., COL6A3, COL1A1, COL1A2), coagulation genes (F5, F13A1) as well as thrombosis-related genes (CD36, ADAMTS9, GAS6). In smokers, we identified deregulated genes that show tissue non-specific induction and may be considered as general biomarkers of tobacco smoke exposure. Further, we also found genes specifically deregulated in the exposed placentas. Functional annotation analysis suggested processes and pathways affected by tobacco smoke exposure that may represent molecular mechanisms of smoke-induced placental abnormalities.

  20. Placental immune response to apple allergen in allergic mothers.

    PubMed

    Abelius, Martina Sandberg; Enke, Uta; Varosi, Frauke; Hoyer, Heike; Schleussner, Ekkehard; Jenmalm, Maria C; Markert, Udo R

    2014-12-01

    The immunological milieu in the placenta may be crucial for priming the developing foetal immune system. Early imbalances may promote the establishment of immune-mediated diseases in later life, including allergies. The initial exposure to allergens seems to occur in utero, but little is known about allergen-induced placental cytokine and chemokine release. The release of several cytokines and chemokines from placenta tissue after exposure to mast cell degranulator compound 48/80 or apple allergen in placentas from allergic and healthy mothers was to be analysed. Four placentas from women with apple allergy and three controls were applied in a placental perfusion model with two separate cotyledons simultaneously perfused with and without apple allergen (Mal d 1). Two control placentas were perfused with compound 48/80. In outflow, histamine was quantified spectrophotofluorometrically, IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ by a cytometric multiplex bead array and IL-13 and CXCL10, CXCL11, CCL17 and CCL22 with an in-house multiplex Luminex assay. Compound 48/80 induced a rapid release of histamine, CXCL10, CXCL11, CCL17 and CCL22, but not of the other factors. Apple allergen induced a time-dependent release of IL-6 and TNF, but not of histamine, in placentas of women with apple allergy compared with the unstimulated cotyledon. CCL17 levels were slightly increased after allergen stimulation in control placentas. Allergens can induce placental cytokines and chemokines distinctly in allergic and healthy mothers. These mediators may affect the prenatal development of the immune system and modify the risk of diseases related to immune disorders in childhood such as allergies.

  1. Selection for placental efficiency in swine: genetic parameters and trends.

    PubMed

    Mesa, H; Safranski, T J; Fischer, K A; Cammack, K M; Lamberson, W R

    2005-05-01

    The objectives of this study were to estimate response to divergent selection for an index of placental efficiency in swine, and to evaluate the effect of placental efficiency on litter size. The selection index (SI) included total born (TB), birth weight (BRWT), and placental weight (PW), and was designed to increase in the high line (H) or decrease in the low line (L) the efficiency of the placental function (PE), defined as the ratio BRWT:PW. (Co)variance components were estimated for direct and maternal additive effects by using an animal model with MTDFREML procedures. Estimated breeding values were calculated by using records on individual BRWT (n = 2,111), PW (n = 2,006), PE (n = 1,677), and SI (n = 1,677). Litter traits were evaluated using records on 193 litters. The model included the fixed effects of contemporary group for all traits, with the addition of sex for individual traits and parity for litter traits. Litter was fitted as an uncorrelated random effect for all traits, and TB was used as a linear and quadratic covariate for BRWT, PW, and PE. Direct heritability estimates from single-trait models were 0.03, 0.25, 0.18, 0.11, and 0.08 for BRWT, PW, PE, SI, and TB, respectively. Estimated breeding values were compared between lines by using a model including generation, line within generation, and replicate within line as the error term. Estimates of genetic divergence were 20.7 +/- 2.7 g, 0.24 +/- 0.03, 0.11 +/- 0.02, and 0.07 +/- 0.02 per generation for PW, PE, SI, and TB, respectively (P < 0.01), but divergence was not significant for BRWT. At Generation 4, direct EBV was higher in L than in H for PW (55.9 +/- 8.7 vs. -24.2 +/- 9.5 g, respectively; P < 0.01) and higher in H than in L for PE (0.58 +/- 0.10 vs. -0.35 +/- 0.09 g, respectively; P < 0.01). However, EBV was not different for BRWT, SI, or TB. These results indicate that PW and PE are susceptible to change by genetic selection; however, the correlated response in TB was an unexpected

  2. [Impairments of placental amino acid metabolism in fetal growth restriction].

    PubMed

    Pogorelova, T N; Gunko, V O; Avrutskaya, V V; Kaushanskaya, L V; Durnitsyna, O A

    2017-05-01

    The content of the amino acids in the placenta during physiological pregnancy and fetal growth restriction (FGR) has been investigated my means of the method of ion-exchange chromatography. It has been found that in FGR the placental amino acid pool is characterized by a decreased content of arginine, proline, alanine, serine, cysteine, methionine, tryptophan, leucine, threonine, tyrosine, phenylalanine, glutamine and an increased content of dicarboxylic amino acids, lysine, histidine and glycine. These changes are accompanied by altered activity of some enzymes of amino acid metabolism, and the degree of these changes correlates with the level of corresponding amino acids.

  3. Extensive intron gain in the ancestor of placental mammals.

    PubMed

    Kordiš, Dušan

    2011-11-23

    Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for reconstructing intron evolution. The findings of this comprehensive

  4. Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders.

    PubMed

    Davis-Anderson, Katie L; Berger, Sebastian; Lunde-Young, Emilie R; Naik, Vishal D; Seo, Heewon; Johnson, Greg A; Steen, Hanno; Ramadoss, Jayanth

    2017-09-01

    Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model. Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day [GD] 5 to 10; 6.0 g/kg, GD 11 to 19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash-frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10-kDa spin filter, and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer. Mass spectrometry (MS) analysis identified 2,285 placental proteins based on normalized spectral counts and 2,000 proteins by intensity-based absolute quantification. Forty-five placental proteins were significantly (p < 0.05) altered by gestational alcohol exposure by both quantification approaches. These included proteins directly related to alcohol metabolism; specific isoforms of alcohol dehydrogenase and aldehyde dehydrogenase were up-regulated in the alcohol group. Ingenuity analysis identified ethanol degradation as the most significantly altered canonical pathway in placenta, and fetal/organ development as most altered function, with increased risk for metabolic, neurological, and cardiovascular diseases. Physiological roles of the significantly altered proteins were related to early pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions. We conclude that the placenta is a valuable organ not only to understand FASD etiology but it may also serve as a diagnostic tool to identify novel biomarkers for detecting

  5. Selective reduction of the disulfide bonds of ovine placental lactogen.

    PubMed

    Caridad, J J; Wolfenstein-Todel, C

    1988-01-01

    Reduction and carbamidomethylation of two of the three disulfide bridges of ovine placental lactogen was accomplished by the use of 20-fold molar excess of dithiothreitol over protein disulfide content. The derivative retained its binding capacity to somatogenic as well as lactogenic rat liver receptors, although the latter was somewhat diminished. The two disulfide bonds exposed to the reducing agent are those located near the carboxy- and amino-terminus, while the larger loop remained intact after reduction. This behaviour is similar to that of bovine growth hormone, where the larger loop was also more resistant to reduction.

  6. Extensive intron gain in the ancestor of placental mammals

    PubMed Central

    2011-01-01

    Background Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. Results A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. Conclusions This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for reconstructing intron evolution. The

  7. Placental DEPTOR as a stress sensor during pregnancy.

    PubMed

    Mparmpakas, Dionisis; Zachariades, Elena; Goumenou, Anastasia; Gidron, Yori; Karteris, Emmanouil

    2012-04-01

    DEPTOR [DEP-domain-containing and mTOR (mammalian target of rapamycin)-interacting protein] is a modulator of mTOR signalling that binds to mTORC (mTOR complex) 1 and mTORC2. However, to date, the precise functions of DEPTOR are not fully elucidated, particularly in reproductive tissues where mTOR acts as a placental nutrient sensor. Pregnancy is associated with major physiological and psychosocial changes and adaptation to these changes is crucial for normal fetal development. In the present study, we tested the hypothesis that maternal stress can affect mTOR signalling at term, and, as a result, influence placental growth. We first investigated the expression of DEPTOR, mTOR, rictor (rapamycin-insensitive companion of mTOR) and raptor (regulatory associated protein of mTOR) from human placentas (n=23) using Q-PCR (quantitative PCR), and correlated these data to days of pregnancy and maternal stress, as well as placental and fetal weight. Maternal and fetal cortisol levels were also measured. JEG-3 and BeWo cells, used as placental in vitro models, were treated with cortisol and DEPTOR expression was assessed using Q-PCR. DEPTOR appears to be the predominant transcript in the human placenta compared with mTOR, rictor and raptor in both term (n=13) and preterm (n=10) placentas as assessed by Q-PCR. There was a significantly lower level only of log-DEPTOR gene expression in the high stress group (-1.34) than in the low stress group (0.07; t₂₀=2.41, P=0.026). Interestingly, mothers with high stress had significantly elevated levels of cortisol (8555 pg/ml) compared with those with low stress (4900 pg/ml). We then tested the hypothesis that cortisol can directly affect DEPTOR expression. When BeWo cells were treated with cortisol 10, 100 and 1000 nM, the expression of DEPTOR was significantly down-regulated by 50, 41 and 39% (all P<0.05) respectively when compared with basal levels. Treatment of JEG-3 cells with cortisol, led to a significant decrease of DEPTOR

  8. Evidence that fetal death is associated with placental aging.

    PubMed

    Maiti, Kaushik; Sultana, Zakia; Aitken, Robert J; Morris, Jonathan; Park, Felicity; Andrew, Bronwyn; Riley, Simon C; Smith, Roger

    2017-10-01

    The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the

  9. Making the impossible possible: rooting the tree of placental mammals.

    PubMed

    Teeling, Emma C; Hedges, S Blair

    2013-09-01

    Untangling the root of the evolutionary tree of placental mammals has been nearly an impossible task. The good news is that only three possibilities are seriously considered. The bad news is that all three possibilities are seriously considered. Paleontologists favor a root anchored by Xenarthra (e.g., sloths and anteater), whereas molecular evolutionists have favored the two other possible roots: Afrotheria (e.g., elephants, hyraxes, and tenrecs) and Atlantogenata (Afrotheria + Xenarthra). Now, two groups of researchers have scrutinized the largest available genomic data sets bearing on the question and have come to opposite conclusions, as reported in this issue of Molecular Biology and Evolution. Needless to say, more research is needed.

  10. Effect of Fetal Size on Fetal Placental Hyaluronan and Hyaluronoglucosaminidases Throughout Gestation in the Pig

    USDA-ARS?s Scientific Manuscript database

    Previous results indicated that the trophoblast-endometrial epithelial cell bilayer of porcine placenta undergoes microscopic folding during gestation, and the folded bilayer is embedded in placental stroma. We hypothesized that hyaluronan was a component of placental stroma, and that hyaluronidases...

  11. A novel software-based technique for quantifying placental calcifications and infarctions from ultrasound

    NASA Astrophysics Data System (ADS)

    Ryan, John T.; McAuliffe, Fionnuala; Higgins, Mary; Stanton, Marie; Brennan, Patrick

    2008-03-01

    In obstetrics, antenatal ultrasound assessment of placental morphology comprises an important part of the estimation of fetal health. Ultrasound analysis of the placenta may reveal abnormalities such as placental calcification and infarcts. Current methods of quantification of these abnormalities are subjective and involve a grading system of Grannum stages I-III. The aim of this project is to develop a software tool that quantifies semi-automatically placental ultrasound images and facilitates the assessment of placental morphology. We have developed a 2D ultrasound imaging software tool that allows the obstetrician or sonographer to define the placental region of interest. A secondary reference map is created for use in our quantification algorithm. Using a slider technique the user can easily define an upper threshold based on high intensity for calcification classification and a lower threshold to define infarction regions based on low intensity within the defined region of interest. The percentage of the placental area that is calcified and also the percentage of infarction is calculated and this is the basis of our new metric. Ultrasound images of abnormal and normal placentas have been acquired to aid our software development. A full clinical prospective evaluation is currently being performed and we are currently applying this technology to the three-dimensional ultrasound domain. We have developed a novel software-based technique for calculating the extent of placental calcification and infarction, providing a new metric in this field. Our new metric may provide a more accurate measurement of placental calcification and infarction than current techniques.

  12. Benign multiple diffuse neonatal hemangiomatosis after a pregnancy complicated by polyhydramnios and a placental chorioangioma.

    PubMed

    Witters, Ingrid; Van Damme, Marie Therèse; Ramaekers, Paul; Van Assche, Frans André; Fryns, Jean Pierre

    2003-01-10

    A male newborn with multiple cutaneous hemangiomatosis is described. Pregnancy was complicated by polyhydramnios and a large placental chorioangioma. After an initial outburst of the hemangiomas in the first two weeks of life, spontaneous and almost complete regression occurred before the age of 3 months. The relationship between hemangiomas and placental chorioangioma is briefly discussed.

  13. Experimentally Induced Placentitis with Streptococcus equi zooepidemicus in Late Gestation Mares: Prevention of Preterm Birth

    USDA-ARS?s Scientific Manuscript database

    Placental infection due to opportunistic pathogens is the most common cause of abortion and premature delivery in horses. However, current therapies used to treat mares with placentitis are based on clinical experience, anecdotal information or on case reports. Thus, the objective of this study was ...

  14. Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

    PubMed Central

    Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

    2013-01-01

    Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

  15. Experimentally Induced Placentitis with Streptococcus equi zooepidemicus in Late Gestation Mares: Prevention of Preterm Birth

    USDA-ARS?s Scientific Manuscript database

    Placental infection due to opportunistic pathogens is the most common cause of abortion and premature delivery in horses. However, current therapies used to treat mares with placentitis are based on clinical experience, anecdotal information or on case reports. Thus, the objective of this study was ...

  16. Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death.

    PubMed

    Man, J; Hutchinson, J C; Heazell, A E; Ashworth, M; Jeffrey, I; Sebire, N J

    2016-11-01

    Placental abnormalities are a common cause of death in stillbirth, ranking second only to unexplained deaths, though there is wide variation in the proportion attributed to placental disease. In clinical practice, interpretation of the significance of placental findings is difficult, since many placental features in stillbirths overlap with those in live births. Our aim was to examine objectively classified placental findings from a series of > 1000 autopsies following intrauterine death in order to evaluate the role of placental histological examination in determining the cause of death. As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for all cases examined between 2005 and 2013 at two tertiary specialist centers in London, UK. Histological findings for placentas were evaluated in relation to the final cause of death. Among 1064 intrauterine deaths, 946 (89%) cases had the placenta submitted for examination as part of the autopsy. Of these, 307 (32%) cases had the cause of death assigned to abnormalities of the placenta, cord or membranes. Around one third of stillbirths (≥ 24 weeks) had some isolated placental histological abnormality identified, many of uncertain significance, a significantly greater proportion than in cases of second-trimester intrauterine fetal demise (P < 0.0001). The cause of death was ascending infection in 176/946 (19%) cases, peaking at 22 weeks' gestation, with significantly more black mothers having ascending infection compared with other ethnicities (P < 0.0001). Maternal vascular malperfusion was the largest category of placental abnormalities in stillbirth, with peak prevalence in the early third trimester. There were 18 (2%) cases with specific histological abnormalities, including chronic histiocytic intervillositis and massive perivillous fibrin deposition. Placental pathologies represent the

  17. Immunohistochemical localization of placental-like alkaline phosphatase in testis and germ-cell tumors using monoclonal antibodies.

    PubMed Central

    Paiva, J.; Damjanov, I.; Lange, P. H.; Harris, H.

    1983-01-01

    Six monoclonal antibodies raised against the human placental alkaline phosphatase (ALP) recognizing distinct antigenic determinants on the surface of this isozyme were used for immunohistochemical studies of adult and fetal human testes and testicular germ-cell tumors. ALP reacting with all six antibodies was defined as placental, whereas ALP reacting with some but not all antibodies was labeled as placental-like. ALP reacting with one of the monoclonal antibodies that recognizes a determinant common to intestinal and placental ALP was tentatively considered probably intestinal, unless it reacted with any other monoclonal placental specific antibody. Using this approach, the authors have identified placental ALP in 4 of 7 seminomas, 3 of 7 tumors composed in part or fully of embryonal carcinoma, and 1 yolk sac carcinoma. Placental-like ALP was identified in 2 additional seminomas and 4 embryonal carcinoma-containing tumors, whereas 1 seminoma and 1 benign teratoma were devoid of either placental or placental-like ALP. Trophoblastic giant cells in 2 seminomas and 3 teratocarcinomas expressed only the antigenic determinant common to placental and intestinal ALP. The authors thus show that testicular tumor cells may express either placental or placental-like ALP and that in some instances, the tumor isozyme is antigenically different from ALP found on either fetal or adult testicular germ cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:6846501

  18. IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells.

    PubMed

    Ackerman, W E; Bulmer, J N; Carter, A M; Chaillet, J R; Chamley, L; Chen, C P; Chuong, E B; Coleman, S J; Collet, G P; Croy, B A; de Mestre, A M; Dickinson, H; Ducray, J; Enders, A C; Fogarty, N M E; Gauster, M; Golos, T; Haider, S; Heazell, A E; Holland, O J; Huppertz, B; Husebekk, A; John, R M; Johnsen, G M; Jones, C J P; Kalionis, B; König, J; Lorenzon, A R; Moffett, A; Moreira de Mello, J C; Nuzzo, A M; Parham, P; Parolini, O; Petroff, M G; Pidoux, G; Ramírez-Pinilla, M P; Robinson, W P; Rolfo, A; Sadovsky, Y; Soma, H; Southcombe, J H; Tilburgs, T; Lash, G E

    2012-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines.

    PubMed

    Adibi, Jennifer; Burton, Graham J; Clifton, Vicki; Collins, Sally; Frias, Antonio E; Gierman, Lobke; Grigsby, Peta; Jones, Helen; Lee, Cheryl; Maloyan, Alina; Markert, Udo R; Morales-Prieto, Diana M; Murthi, Padma; Myatt, Leslie; Pollheimer, Jurgen; Roberts, Victoria; Robinson, Wendy; Salafia, Carolyn; Schabel, Matthias; Shah, Dinesh; Sled, John; Vaillancourt, Cathy; Weber, Maja; O'Tierney-Ginn, Perrie F

    2017-03-06

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.

  20. Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia-reperfusion injury.

    PubMed

    Jones, Megan L; Mark, Peter J; Waddell, Brendan J

    2013-12-01

    Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders. Oxidative stress occurs when excess reactive oxygen species (ROS) damages cellular components, an outcome limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) also limits ROS production. We recently reported that maternal dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation reduced placental oxidative damage and enhanced fetal and placental growth in the rats. Here, we examined the effect of n-3 PUFAs on placental antioxidant defences and whether n-3 PUFA supplementation could prevent growth restriction induced by placental ischaemia-reperfusion (IR), a known inducer of oxidative stress. Rats were fed either standard or high-n-3 PUFA diets from day 1 of pregnancy. Placentas were collected on days 17 and 22 in untreated pregnancies (term=day 23) and at day 22 following IR treatment on day 17. Expression of several antioxidant enzyme genes (Sod1, Sod2, Sod3, Cat, Txn1 and Gpx3) and Ucp2 was measured by quantitative RT-PCR in the placental labyrinth zone (LZ) and junctional zone (JZ). Cytosolic superoxide dismutase (SOD), mitochondrial SOD and catalase (CAT) activities were also analyzed. Maternal n-3 PUFA supplementation increased LZ mRNA expression of Cat at both gestational days (2- and 1.5-fold respectively; P<0.01) and female Sod2 at day 22 (1.4-fold, P<0.01). Cytosolic SOD activity increased with n-3 PUFA supplementation at day 22 (1.3-fold, P<0.05). Sod1 and Txn1 expression decreased marginally (30 and 22%, P<0.05). JZ antioxidant defences were largely unaffected by diet. Despite increased LZ antioxidant defences, maternal n-3 PUFA supplementation did not protect against placental IR-induced growth restriction of the fetus and placental LZ.

  1. Placental tumor (chorioangioma) as a cause of polyhydramnios: a case report

    PubMed Central

    Abdalla, Nabil; Bachanek, Michal; Trojanowski, Seweryn; Cendrowski, Krzysztof; Sawicki, Wlodzimierz

    2014-01-01

    Placental chorioangioma is the most common type of placental tumor. It is usually symptomless and may be associated with serious maternal and fetal complication when it reaches a large size. We presented a case of an angiomatous type of placental hemangioma diagnosed in the second trimester of pregnancy in a patient with polyhydramnios. A normal volume of amniotic fluid was successfully achieved by three amnioreductions with conservative management. The size of the placental tumor remained the same from the time of diagnosis to the end of pregnancy. A term labor was uncomplicated and a healthy newborn was delivered. Macroscopic and microscopic examination of the placenta confirmed the diagnosis. Despite the rarity of placental tumors, they should be considered as differential diagnosis in cases of polyhydramnios. PMID:25429242

  2. The effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal anthropometric parameters and placental weight.

    PubMed

    Sakar, M N; Balsak, D; Verit, F F; Zebitay, A G; Buyuk, A; Akay, E; Turfan, M; Demir, S; Yayla, M

    2016-05-01

    In Islamic religion, daytime fasting during the month called Ramadan is an annual practice. In this study, we aimed to investigate the effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal growth parameters. A prospective case-control study was conducted in Diyarbakir and Istanbul, Turkey. The sample size of fasting group was 168 and that of non-fasting group was 170. Demographic characteristics, obstetrics ultrasonographic findings and laboratory parameters of the participants were recorded. Neonatal anthropometric parameters and placental weight were noted. The mean placental weight was significantly higher in the fasting group (p = 0.037). Also, in the fasting group, pregnant women with hypoalbuminaemia had significantly higher placental weight (p = 0.009). In conclusion, the mean placental weight in the fasting group was significantly higher. Also a significant correlation between placental weight and maternal serum albumin level was observed in the fasting group.

  3. Pre-clinical and clinical development of the first placental malaria vaccine.

    PubMed

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G; Nielsen, Morten A

    2017-06-01

    Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical vaccine development. However, all papers from these searches were not systematically included. Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine.

  4. Intact feto-placental growth in microRNA-210 deficient mice.

    PubMed

    Krawczynski, Kamil; Mishima, Takuya; Huang, Xin; Sadovsky, Yoel

    2016-11-01

    MicroRNA-210 (miR-210) has been implicated in homeostatic adaptation during hypoxia. We hypothesized that miR-210 deficiency impacts feto-placental growth. As expected, mir-210 knockout (ko) mice exhibited markedly reduced placental miR-210 expression, compared to wild-type (wt) mice. Mating of mir-210 heterozygotes resulted in near Mendelian progeny distribution, with insignificant differences between wt and ko animals with regard to embryo or placental weight and gross morphology. Intriguingly, exposure of mice to non-severe hypoxia (O2 = 12%) between E11.5-E17.5 reduced placental miR-210 expression, with slight expression changes of some miR-210 target mRNAs. Thus, miR-210 is likely dispensable for feto-placental growth in normoxia or non-severe hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A new liquid chromatography-tandem mass spectrometry method for determination of parabens in human placental tissue samples.

    PubMed

    Jiménez-Díaz, I; Vela-Soria, F; Zafra-Gómez, A; Navalón, A; Ballesteros, O; Navea, N; Fernández, M F; Olea, N; Vílchez, J L

    2011-05-15

    Endocrine disruptors are a group of organic compounds widely used, which are ubiquitous in the environment and in biological samples. The main effect of these compounds is associated with their ability to mimic or block the action of natural hormones in living organisms, including humans. Parabens (esters of p-hydroxybenzoic acid) belong to this group of compounds. In this work, we propose a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to asses the presence of parabens most commonly used in industrial applications (methyl-, ethyl-, propyl- and butyl-paraben) in samples of human placental tissue. The method involves the extraction of the analytes from the samples using ethyl acetate, followed by a clean-up step using centrifugation prior to their quantification by LC-MS/MS using an atmospheric pressure chemical ionization (APCI) interface in the negative mode. Deuterated bisphenol A (BPA-d(16)) was used as surrogate. Found detection limits (LOD) ranged from 0.03 to 0.06 ng g(-1) and quantification limits (LOQ) from 0.1 to 0.2 ng g(-1), while inter- and intra-day variability was under 13.8%. The method was validated using standard addition calibration and a spike recovery assay. Recovery rates for spiked samples ranged from 82% to 108%. This method was satisfactorily applied for the determination of parabens in 50 placental tissue samples collected from women who live in the province of Granada (Spain).

  6. Influence of the duration of calving and obstetric assistance on the placental retention index in Holstein dairy cows.

    PubMed

    Vannucchi, Camila I; Silva, Liege G; Lúcio, Cristina F; Veiga, Gisele A L

    2017-03-01

    The aim of this study is to evaluate the influence of duration of calving and obstetric assistance on retained placenta incidence of high milk production Holstein cows. Experimental groups were determined according to the duration of the expulsive phase of calving: 2 h (n = 16), 2-4 h (n = 16) and >4 h (n = 12), and additionally allocated in two sub-groups: spontaneous calving (n = 22) and intervention calving (n = 22). Diagnosis of retained placenta was considered with a threshold of 8 h after the expulsive phase. Cows without obstetric intervention, with labor duration of 2 h, presented reduced time needed for placental release, in comparison to those with obstetric assistance. In the 2-4 h group and >4 h, there was no statistical difference. The 2 h and 2-4 h groups with intervention and the spontaneous >4 h group were considered retained placenta groups. On the other hand, performing obstetric intervention when calving period was superior to 4 h nulled the occurrence of retention of fetal membranes. As a conclusion, obstetric assistance predisposes placental retention to calving with <2 h of duration in dairy cows. Conversely, when calving is more than 4 h, performing fetal extraction has a beneficial influence on preventing retained placenta.

  7. Effect of young maternal age and skeletal growth on placental growth and development.

    PubMed

    Hayward, C E; Greenwood, S L; Sibley, C P; Baker, P N; Jones, R L

    2011-12-01

    Teenagers are susceptible to delivering small-for-gestational-age infants. Previous studies implicate continued skeletal growth as a contributory factor, and impaired placental development was the primary cause of fetal growth restriction in growing adolescent sheep. The aims of this study were to examine the impact of young maternal age and growth on placental development. Placentas were collected from 31 teenagers, of which 12 were growing and 17 non-growing based on knee height measurements. An adult control group (n = 12) was included. Placental weight and morphometric measurements of villous, syncytiotrophoblast, fibrin and vessel areas, as well as indices of proliferation and apoptosis, were analysed in relation to maternal growth and age. Growing teenagers had a higher birthweight:placental weight ratio than non-growing teenagers (p < 0.05). Villous area, syncytial area, fibrin content, vascularisation and cell turnover did not differ between growing and non-growing teenagers. There were no differences in placental weight or morphometry between adult and teenage pregnancies. Maternal smoking, a potential confounding factor, did not exert a major influence on the placental parameters examined, except for a stimulatory effect on placental proliferation (p < 0.05) and syncytial knot formation (p < 0.05). We were unable to detect any major differences in placental size or composition between growing and non-growing teenagers. Birthweight:placental weight ratio was higher in growing compared to non-growing teenagers. This suggests that maternal growth may affect placental function rather than development, and is consistent with our recent observations that maternal growth was not detrimental to fetal growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Adaptations in placental phenotype depend on route and timing of maternal dexamethasone administration in mice.

    PubMed

    Vaughan, Owen R; Sferruzzi-Perri, Amanda N; Coan, Philip M; Fowden, Abigail L

    2013-10-01

    Synthetic glucocorticoids, like dexamethasone (dex), restrict growth of the fetus and program its adult physiology, in part by altering placental phenotype. The route and timing of dex administration determine the fetal and adult outcomes, but whether these factors affect placental phenotype remains unknown. This study compared placental morphology, amino acid transport, and gene expression in mice given dex orally or by subcutaneous injection over the periods of most rapid placental (Days [D] 11-16) or fetal (D14-19) growth (term is D21). Compared with untreated and saline-injected controls, both dex treatments reduced placental weight at D16 and 19 and fetal weight and total labyrinthine volume at D19 to a similar extent. Only oral dex treatment from D11 to D16 reduced labyrinthine fetal capillary volume on D16 and increased placental ¹⁴C-methylaminoisobutyric acid (MeAIB) clearance at D19, 3 days after treatment ended. Neither route of dex treatment altered placental expression of Slc38a, Hsd11b, or the glucocorticoid receptor, Nr3c1, at D16. In contrast, both routes of dex treatment from D14 to D19 increased placental Hsd11b2 expression and labyrinthine maternal vessel volume. Furthermore, injection per se altered placental expression of Nr3c1, Hsd11b1, and specific Slc38a isoforms in an age-related manner. Overall, MeAIB clearance was not related to Slc38a transporter expression but was correlated inversely with maternal corticosterone concentrations when dex was undetectable in maternal plasma at D19. The effects of dex on placental phenotype, therefore, depend on both the route and timing of administration and may relate to local glucocorticoid availability during and after the treatment period.

  9. In vivo targets of human placental micro-vesicles vary with exposure time and pregnancy.

    PubMed

    Tong, Mancy; Chen, Qi; James, Joanna L; Wise, Michelle R; Stone, Peter R; Chamley, Lawrence W

    2017-06-01

    Throughout human gestation, the placenta extrudes vast quantities of extracellular vesicles (EVs) of different sizes into the maternal circulation. Although multinucleated macro-vesicles are known to become trapped in the maternal lungs and do not enter the peripheral circulation, the maternal organs and cells that smaller placental micro-vesicles interact with in vivo remain unknown. This study aimed to characterise the interaction between placental micro-vesicles and endothelial cells in vitro and to elucidate which organs placental micro-vesicles localise to in vivo Placental macro- and micro-vesicles were isolated from cultured human first trimester placental explants by sequential centrifugation and exposed to human microvascular endothelial cells for up to 72 h. In vivo, placental macro- and micro-vesicles were administered to both non-pregnant and pregnant CD1 mice, and after two or 30 min or 24 h, organs were imaged on an IVIS Kinetic Imager. Placental EVs rapidly interacted with endothelial cells via phagocytic and clathrin-mediated endocytic processes in vitro, with over 60% of maximal interaction being achieved by 30 min of exposure. In vivo, placental macro-vesicles were localised exclusively to the lungs regardless of time of exposure, whereas micro-vesicles were localised to the lungs, liver and kidneys, with different distribution patterns depending on the length of exposure and whether the mouse was pregnant or not. The fact that placental EVs can rapidly interact with endothelial cells and localise to different organs in vivo supports that different size fractions of placental EVs are likely to have different downstream effects on foeto-maternal communication. © 2017 Society for Reproduction and Fertility.

  10. Placental expression and molecular characterization of aromatase cytochrome P450 in the spotted hyena (Crocuta crocuta).

    PubMed

    Conley, A J; Corbin, C J; Browne, P; Mapes, S M; Place, N J; Hughes, A L; Glickman, S E

    2007-07-01

    At birth, the external genitalia of female spotted hyenas (Crocuta crocuta) are the most masculinized of any known mammal, but are still sexually differentiated. Placental aromatase cytochrome P450 (P450arom) is an important route of androgen metabolism protecting human female fetuses from virilization in utero. Therefore, placental P450arom expression was examined in spotted hyenas to determine levels during genital differentiation, and to compare molecular characteristics between the hyena and human placental enzymes. Hyena placental P450arom activity was determined at gestational days (GD) 31, 35, 45, 65 and 95 (term, 110), and the relative sensitivity of hyena and human placental enzyme to inhibition by the specific inhibitor, Letrozole, was also examined. Expression of hyena P450arom in placenta was localized by immuno-histochemistry, and a full-length cDNA was cloned for phylogenetic analysis. Aromatase activity increased from GD31 to a peak at 45 and 65, apparently decreasing later in gestation. This activity was more sensitive to inhibition by Letrozole than was human placental aromatase activity. Expression of P450arom was localized to syncytiotrophoblast and giant cells of mid-gestation placentas. The coding sequence of hyena P450arom was 94% and 86% identical to the canine and human enzymes respectively, as reflected by phylogenetic analyses. These data demonstrate for the first time that hyena placental aromatase activity is comparable to that of human placentas when genital differentiation is in progress. This suggests that even in female spotted hyenas clitoral differentiation is likely protected from virilization by placental androgen metabolism. Decreased placental aromatase activity in late gestation may be equally important in allowing androgen to program behaviors at birth. Although hyena P450arom is closely related to the canine enzyme, both placental anatomy and P450arom expression differ. Other hyaenids and carnivores must be investigated to

  11. Intrapartum anti-disseminated intravascular coagulation therapy leading to successful vaginal delivery following intrauterine fetal death caused by placental abruption: a case report.

    PubMed

    Honda, Michiko; Matsunaga, Shigetaka; Era, Sumiko; Takai, Yasushi; Baba, Kazunori; Seki, Hiroyuki

    2014-12-23

    Disseminated intravascular coagulation due to placental abruption with intrauterine fetal death is not uncommon. It can result in increased maternal mortality rates and the need for hysterectomy or greater transfusion volumes if the delivery is not completed within six to eight hours. However, consensus is lacking regarding the delivery approach for cases in which delivery is prolonged. A 37-year-old Japanese woman was transported to our tertiary center two and a half hours after the onset of labor because of a diagnosis of placental abruption with intrauterine fetal death at 40 weeks and three days' gestation. On arrival, although severe hypofibrinogenemia was observed, there was no external hemorrhage. Because her cervical canal dilation was good (Bishop score, 7), labor was induced using oxytocin. Anti-disseminated intravascular coagulation therapy was simultaneously started via transfusion. After her hypofibrinogenemia resolved, delivery progressed rapidly, and the fetus was delivered approximately 10 hours after the onset. To reduce postpartum hemorrhage, 6g of fibrinogen concentrate and tranexamic acid, an antifibrinolytic agent, were administered immediately before extraction of the dead fetus and placenta. Although the amount of intrapartum hemorrhage was 1824g, there was no abnormal bleeding after delivery, and our patient was discharged three days later. In cases of placental abruption complicated with disseminated intravascular coagulation, intrapartum administration of coagulation factors can simultaneously promote effective labor and correct hypofibrinogenemia, enabling minimally invasive vaginal delivery.

  12. Placental passage of antiepileptic drugs at delivery and neonatal outcomes.

    PubMed

    Bank, Anna M; Stowe, Zachary N; Newport, D Jeffrey; Ritchie, James C; Pennell, Page B

    2017-05-01

    Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical-to-maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical-to-maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical-to-maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical-to-maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  13. Probability distributions for measures of placental shape and morphology.

    PubMed

    Gill, J S; Woods, M P; Salafia, C M; Vvedensky, D D

    2014-03-01

    Birthweight at delivery is a standard cumulative measure of placental growth, but is a crude summary of other placental characteristics, such as, e.g., the chorionic plate size, and the shape and position of the umbilical cord insertion. Distributions of such measures across a cohort reveal information about the developmental history of the chorionic plate which is unavailable from an analysis based solely on the mean and standard deviation. Various measures were determined from digitized images of chorionic plates obtained from the pregnancy, infection, and nutrition study, a prospective cohort study of preterm birth in central North Carolina between 2002 and 2004. Centroids (geometric centers) and umbilical cord insertions were taken directly from the images. Chorionic plate outlines were obtained from an interpolation based on a Fourier series, while eccentricity (of the best-fit ellipse), skewness, and kurtosis were determined from the method of moments. Histograms of each variable were compared against the normal, lognormal, and Lévy distributions. Only a single measure (eccentricity) followed a normal distribution. All others followed lognormal or 'heavy-tailed' distributions for moderate to extreme deviations from the mean, where the relative likelihood far exceeded those of a normal distribution.

  14. Perspectives of SLIT/ROBO signaling in placental angiogenesis.

    PubMed

    Liao, Wu-xiang; Wing, Deborah A; Geng, Jian-Guo; Chen, Dong-bao

    2010-09-01

    A novel family of evolutionally conserved neuronal guidance cues, including ligands (i.e., Slit, netrin, epherin, and semaphorin) and their corresponding receptors (i.e., Robo, DCC/Unc5, Eph and plexin/ neuropilin), has been identified to play a crucial role in axon pathfinding and branching as well as neuronal cell migration. The presence of commonalities in both neural and vascular developments has led to some exciting discoveries recently, which have extended the functions of these systems to vascular formation (vasculogenesis) and development (angiogenesis). Some of these ligands and receptors have been found to be expressed in the vasculature and surrounding tissues in physiological and pathological conditions. It is postulated that they regulate the formation and integrity of blood vessels. In particular, it has been shown that the Slit/Robo pair plays a novel role in angiogenesis during tumorigenesis and vascular formation during embryogenesis. Herein we summarize briefly the characteristics of this family of neuronal guidance molecules and discuss the extra-neural expression and function of the Slit/Robo pair in angiogenesis in physiological and pathological settings. We report expression of Robo1 protein in capillary endothelium and co-expression of Slit2 and Robo1 proteins in syncytiotrophoblast in healthy term human placental villi. These cellular expression patterns implicate that the Slit/Robo signaling plays an autocrine and/or paracrine role in angiogenesis and trophoblast functions. We also speculate a possible role of this system in pathophysiological placental angiogenesis.

  15. Bovine placental lactogen: isolation purification and measurement in biological fluids

    SciTech Connect

    Wallace, C.R.

    1986-01-01

    Studies were conducted to isolate and purify bovine placental lactogen (bPL) and to develop a radioimmunoassay to this protein. Bovine placental lactogen was isolated from culture medium after a 24 hr culture of fetal cotyledonary tissue. Cotyledonary explants were stimulated to secrete bPL by either addition of bovine growth hormone (NIH-B8) to the medium or co-culture of cotyledon and caruncular tissue. Production of bPL was greatly affected by explant size and 70% of that produced in a 48 hr culture was released in the first 12 hr. Purification of bPL was accomplished using a column chromatographic scheme that involved gel filtration, ion exchange and chromatofocusing chromatography. A radioimmunoassay to bPL was developed using an antibody raised at the USDA Beltsville (F56). Dose response curves of amniotic or allantoic fluid or fetal and maternal serum were parallel to the standard curve and bPL was quantitatively recovered at from 82-125%. Using the radioimmunoassay, samples of amniotic and allantoic fluids and fetal and maternal serum were measured for bPL. Concentrations of bPL ranged from undetectable to 50 ng/ml, with fetal blood having the highest concentrations and amniotic fluid the lowest.

  16. Placental matrix metalloproteinase--1 expression is increased in labor.

    PubMed

    Vu, Thanh-Danae; Yun Feng; Placido, Jessica; Reznik, Sandra E

    2008-04-01

    Matrix metalloproteinases (MMPs) are now known to process a broad spectrum of cell surface molecules and to function in several important biological processes. Testing for differences in gene expression in human placental chorionic villi in the absence or presence of labor, using cDNA microarray analysis, revealed that labor was associated with increased expression of MMP-1 gene expression in 5 placentas collected after term normal spontaneous deliveries compared with 5 placentas collected after term nonlaboring cesarean deliveries. Fibronectin 1 and collagen XVII, 2 other proteins involved in the homeostasis of the extracellular matrix, were also found to be upregulated in labor. MMP-1 was further tested in individual samples and found to be consistently overexpressed in labor. While previous microarray analyses have focused on either uterine tissue or the fetal membranes, the data presented here indicate for the first time that placental chorionic villus genes are likely to affect the initiation of parturition through altered processing of cell surface molecules by MMP-1.

  17. Observer reliability in assessing placental maturity by histology.

    PubMed Central

    Khong, T Y; Staples, A; Bendon, R W; Chambers, H M; Gould, S J; Knowles, S; Shen-Schwarz, S

    1995-01-01

    AIMS--To evaluate the ability of five experienced perinatal pathologists to assess placental maturity reliably by histology. METHODS--Twenty four haematoxylin and eosin slides, six each from placentas of 27, 31, 35, and 39 weeks' gestation, were circulated to five pathologists on three separate occasions. The slides were labelled with the correct or incorrect gestational ages. RESULTS--The mean absolute error over all 360 readings was 2.72 weeks. Only 54% of the slides were assessed within two weeks of the correct gestation. Pathologist tended to overestimate younger gestations and underestimate older gestations. Two, and possibly three, pathologist were influenced by the gestational age state on the label. One pathologist, who did not appear to be influenced by the label, was more accurate in diagnosing gestation of the placentas than other colleagues. CONCLUSIONS--Experienced pathologists can have difficulty in assessing the villous maturity of placentas by histology. They can also be influenced by clinical information provided, such as gestational age. Other observer reliability studies must address the issue of the influence of labelled information on observer variation. A difference in maturation would have to be of a six week magnitude to have a chance of being detected by current methods. This may limit the value of the histological diagnosis of placental dysmaturity as a surrogate marker for uteroplacental ischaemia. PMID:7629287

  18. Placental site trophoblastic tumor and choriocarcinoma: an unusual presentation.

    PubMed

    Gari, Abdulrahim

    2015-11-23

    Mixed trophoblastic tumor composed of choriocarcinoma and placental site trophoblastic tumor was diagnosed on histopathology slides review, is a very rare mixed tumor and cured after adjuvant chemotherapy. Twenty-nine years old, Para 2 female presented with 4 months history of irregular vaginal bleeding after an uncomplicated vaginal delivery. Abdominal examination showed 14 weeks uterus with β-hCG level of 14,889 mIU/ml. Slides review confirmed the diagnosis of placental site trophoblastic tumor (PSTT). Patient underwent total abdominal hysterectomy and resection of anterior vaginal wall mass. Post operative (48 h) β-hCG level was 6016 mIU/ml. Final pathology showed mixed trophoblastic tumor composed of choriocarcinoma (CC) and PSTT. Adjuvant chemotherapy started and continued for three cycles after achieving normal β-hCG. PSTT is a rare disease and potentially curable. Differential diagnosis in women presented with vaginal bleeding and a uterine mass in the post partum period must include gestational trophoblastic disease.

  19. Natural history and pregnancy outcome in patients with placental chorioangioma.

    PubMed

    Liu, Haiyan; Gu, Weirong; Li, Xiaotian

    2014-02-01

    To evaluate the natural history and outcome of pregnancies in patients with placental chorioangioma. A total of 16 placentas with a histologic diagnosis of chorioangioma were identified, and the natural history and outcome of pregnancy were evaluated. This study was approved by the Institutional Ethics Committees of our unit, and written informed consent was obtained from all study participants. Thirteen of the 16 cases were associated with a wide variety of fetal complications. Two-thirds of the cases developed complications that either required elective delivery because of fetal distress (n = 4), fetal heart failure (n = 1), oligohydramnion (n = 1), and premature labor of dichorionic twins (n = 1) or resulted in intrauterine fetal death and termination of pregnancy (n = 2). Placental chorioangioma was associated with the development of polyhydramnios, fetal growth restriction, and fetal distress in a significant number of cases. The size, vascularity, and location of the chorioangioma may be three independent factors of maternal and fetal complications. Any of these three factors can influence the outcome of pregnancy. Close antenatal examination should be routinely practiced to allow the timely diagnosis of early fetal heart failure. Copyright © 2013 Wiley Periodicals, Inc.

  20. Immediate post-placental IUD insertion: the expulsion problem.

    PubMed

    Thiery, M; Van Kets, H; Van der Pas, H

    1985-04-01

    This paper reports an evaluation of immediate post-placental insertion of a non-copper (Lippes Loop D) and several copper-bearing IUD models (TCu200, TCu220C, MLCu375, MLCu250, Nova T-PP, DimélysR). Based on the analysis of a total of 2,646 insertions and 55,794 woman-months of experience, we conclude that placement of an IUD within ten minutes of delivery of the placenta is a valuable alternative to interval insertion, because this method is safe and effective. Effectiveness was significantly lower for the Lippes Loop D than for the T- and ML-IUD models tested, the latter showing roughly comparable pertinent event rates. Pertinent event rates for copper IUDs were influenced by the skill of the operator; age of the recipient only had a significant effect on effectiveness, whereas parity had no significant effect on pertinent event rates. The single and still unsolved problem associated with immediate postpartum insertion is the greater likelihood of expulsion compared with interval insertion, and this hazard is significantly much greater for the Loop than for the copper-bearing devices assessed. The evolution of the expulsion rates shows a constant time-relationship. This pattern makes it obvious why follow-up of recipients, at least during the first trimester following insertion, is mandatory if immediate post-placental IUD insertion is to be optimally effective.

  1. Effects of labor on placental fatty acid β oxidation.

    PubMed

    Mendez-Figueroa, Hector; Chien, Edward K; Ji, Huiling; Nesbitt, Nicole L; Bharathi, Sivakama S; Goetzman, Eric

    2013-01-01

    To measure the effect labor exerts on fatty acid (FA) oxidation in term human placentas, and to compare enzymes expression and activity between placenta and liver. Placental samples were collected: (a) scheduled non-labored cesarean section and (b) normal vaginal delivery at or beyond 37 weeks. Long and medium-chain FA oxidation were measured using (3)H-labeled FA, ATP concentration was measured via commercial kit. Activity and expression levels of 11 FA enzymes were measured and results compared to both human and mouse liver. Placentas undergoing labor had significantly decreased palmitate oxidation and ATP levels. Octanoic acid oxidation was 10-fold higher than palmitic acid oxidation. No difference in expression or activity level was detected between the groups. Term human placentas express all the enzymes required to oxidize FA, at a rate 20-fold lower than liver. FA Oxidation is not likely an important placental energy source during labor. Further work is needed to determine the functionality of this pathway in placenta.

  2. Review: Placental syncytiotrophoblast membranes--domains, subdomains and microdomains.

    PubMed

    Riquelme, G

    2011-03-01

    Human placental syncytiotrophoblast (STB) is an epithelium responsible for materno-fetal exchange. Ions play multiple roles in STB, as in other transport epithelia. We have been interested in the character and functional expression of ion channels in STB membrane fractions. Characterization of ion channels and their relationship with different domains, subdomains and microdomains of STB membranes is important to explain the intracellular mechanisms operating in the placental barrier. The aim of this paper is to summarize our work on this subject. We isolated and purified basal membrane (BM) and two fractions from the apical membrane, a classical fraction (MVM) and a light fraction (LMVM). They were used either for reconstitution into giant liposomes or for transplantation into Xenopus oocyte membranes followed by electrophysiological recordings to characterize chloride and cationic channels in STB from term human placenta. In addition, Western blot analysis, using ion channel antibodies, was performed on purified apical and basal membrane fractions. We also reported the presence of two functional microdomains (lipid rafts) in LMVM and MVM, using detergent resistant membranes (DRMs) and cholesterol-sensitive depletion. Moreover we found evidence of cytoskeletal participation in lipid rafts of different composition. Our results contribute to knowledge of the ion channels present in STB membranes and their participation in the physiology of this epithelium in normal and pathological pregnancies.

  3. Cool sperm: why some placental mammals have a scrotum.

    PubMed

    Lovegrove, B G

    2014-05-01

    Throughout the Cenozoic, the fitness benefits of the scrotum in placental mammals presumably outweighed the fitness costs through damage, yet a definitive hypothesis for its evolution remains elusive. Here, I present an hypothesis (Endothermic Pulses Hypothesis) which argues that the evolution of the scrotum was driven by Cenozoic pulses in endothermy, that is, increases in normothermic body temperature, which occurred in Boreotheria (rodents, primates, lagomorphs, carnivores, bats, lipotyphylans and ungulates) in response to factors such as cursoriality and climate adaptation. The model argues that stabilizing selection maintained an optimum temperature for spermatogenesis and sperm storage throughout the Cenozoic at the lower plesiomorphic levels of body temperature that prevailed in ancestral mammals for at least 163 million years. Evolutionary stasis may have been driven by reduced rates of germ-cell mutations at lower body temperatures. Following the extinction of the dinosaurs at the Cretaceous-Palaeogene boundary 65.5 mya, immediate pulses in endothermy occurred associated with the dramatic radiation of the modern placental mammal orders. The fitness advantages of an optimum temperature of spermatogenesis outweighed the potential costs of testes externalization and paved the way for the evolution of the scrotum. The scrotum evolved within several hundred thousand years of the K-Pg extinction, probably associated initially with the evolution of cursoriality, and arguably facilitated mid- and late Cenozoic metabolic adaptations to factors such as climate, flight in bats and sociality in primates.

  4. Placental transport of brevetoxin-3 in CD-1 mice

    PubMed Central

    Benson, Janet M.; Gomez, Andrea P.; Statom, Gloria L.; Tibbetts, Brad M.; Fleming, Lora E.; Backer, Lorraine C.; Reich, Andrew; Baden, Daniel G.

    2008-01-01

    The purpose of this study was to examine the distribution of brevetoxin-3 administered to pregnant dams and to determine the extent of placental transport to fetuses. Twenty-nine pregnant CD-1 mice were administered 3H-brevetoxin-3 (~1.3 μCi/animal; ~2.8 μg compound/kg) by intratracheal instillation on one of gestational days 15–18. Groups of four or five dams were killed at selected times through 48 h post dosing. Four pregnant dams were administered 3H-brevetoxin-3 on gestational day 15 or 16 via osmotic minipump to provide continuous delivery of compound (~0.13 μCi, 7.5 ng compound/day) over a 72-h period after which the dams and fetuses were d. Brevetoxin-associated radioactivity was detected in placentas and fetuses within 0.5 h of intratracheal administration. Concentrations of brevetoxin equivalents in fetuses were approximately 0.3 ng/g throughout the 48-h post dosing, resulting in a calculated dose to fetuses of 19 ng/g-h. Following brevetoxin infusion, concentration of brevetoxin equivalents in fetuses was 0.1 ng/g, lower than that present in most maternal tissues. Results demonstrated placental transport of brevetoxin or its metabolites following maternal acute exposure and repeated low-dose exposure. The consequences of these findings for pregnant women exposed to brevetoxins by inhalation or ingestion remain to be determined. PMID:17011606

  5. Placental ischemia and resultant phenotype in animal models of preeclampsia

    PubMed Central

    LaMarca, Babbette; Amaral, Lorena M; Harmon, Ashlyn C; Cornelius, Denise C; Faulkner, Jessica L; Cunningham, Mark W.

    2016-01-01

    Preeclampsia is new onset (or worsening of preexisting) hypertension that occurs during pregnancy. It is accompanied by chronic inflammation, intrauterine growth restriction, elevated anti-angiogenic factors, and can occur with or without proteinuria. Although the exact etiology is unknown, it is thought that preeclampsia begins early in gestation with reduced uterine spiral artery remodeling leading to decreased vasculogenesis of the placenta as the pregnancy progresses. Soluble factors, stimulated by the ischemic placenta, shower the maternal vascular endothelium and are thought to cause endothelial dysfunction and to contribute to the development of hypertension during pregnancy. Due to the difficulty in studying such soluble factors in pregnant women, various animal models have been designed. Studies from these models have contributed to a better understanding of how factors released in response to placental ischemia may lead to increased blood pressure and reduced fetal weight during pregnancy. This review will highlight various animal models and the major findings indicating the importance of placental ischemia to lead to the pathophysiology observed in preeclamptic patients. PMID:27076345

  6. Impact of placental insufficiency on fetal skeletal muscle growth.

    PubMed

    Brown, Laura D; Hay, William W

    2016-11-05

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Placental Abruption With Delayed Fetal Compromise in Maternal Acetaminophen Toxicity.

    PubMed

    Taney, Juliana; Anastasio, Hannah; Paternostro, Amanda; Berghella, Vincenzo; Roman, Amanda

    2017-07-01

    After maternal acetaminophen overdose, fetal fulminant liver failure, stillbirth, neonatal death, or preterm delivery may occur. A 27-year-old woman, gravida 2 para 1, presented at 28 weeks of gestation after unintentional acetaminophen overdose. Four days after ingestion, her laboratory values worsened, including serum aspartate aminotransferase of 5,460 units/L, alanine aminotransferase of 4,936 units/L, and international normalized ratio of 2.9. On day 6 after ingestion, fetal monitoring showed minimal variability with repetitive variable and late decelerations, which prompted cesarean delivery when a hematoma was noted on the maternal placental surface, consistent with placental abruption. The neonate showed no evidence of hepatic dysfunction. Review of the literature suggests that maternal acetaminophen overdose in the second and third trimester is associated with a 5% incidence of fetal compromise (mostly the result of nonreassuring fetal status leading to delivery or stillbirth) occurring within 6 days of ingestion. Maternal acetaminophen overdose can be associated with delayed fetal compromise, suggesting the importance of continued fetal surveillance several days after ingestion.

  8. IgG Placental Transfer in Healthy and Pathological Pregnancies

    PubMed Central

    Palmeira, Patricia; Quinello, Camila; Silveira-Lessa, Ana Lúcia; Zago, Cláudia Augusta; Carneiro-Sampaio, Magda

    2012-01-01

    Placental transfer of maternal IgG antibodies to the fetus is an important mechanism that provides protection to the infant while his/her humoral response is inefficient. IgG is the only antibody class that significantly crosses the human placenta. This crossing is mediated by FcRn expressed on syncytiotrophoblast cells. There is evidence that IgG transfer depends on the following: (i) maternal levels of total IgG and specific antibodies, (ii) gestational age, (iii) placental integrity, (iv) IgG subclass, and (v) nature of antigen, being more intense for thymus-dependent ones. These features represent the basis for maternal immunization strategies aimed at protecting newborns against neonatal and infantile infectious diseases. In some situations, such as mothers with primary immunodeficiencies, exogenous IgG acquired by intravenous immunoglobulin therapy crosses the placenta in similar patterns to endogenous immunoglobulins and may also protect the offspring from infections in early life. Inversely, harmful autoantibodies may cross the placenta and cause transitory autoimmune disease in the neonate. PMID:22235228

  9. Placental programmed cell death: insights into the role of aquaporins.

    PubMed

    Szpilbarg, N; Castro-Parodi, M; Reppetti, J; Repetto, M; Maskin, B; Martinez, N; Damiano, A E

    2016-01-01

    Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions

  10. Maternal fructose drives placental uric acid production leading to adverse fetal outcomes

    PubMed Central

    Asghar, Zeenat A.; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L.; Moley, Kelle H.

    2016-01-01

    Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans. PMID:27125896

  11. Maternal perception of reduced fetal movements is associated with altered placental structure and function.

    PubMed

    Warrander, Lynne K; Batra, Gauri; Bernatavicius, Giovanna; Greenwood, Susan L; Dutton, Philip; Jones, Rebecca L; Sibley, Colin P; Heazell, Alexander E P

    2012-01-01

    Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM. To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function. Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy. This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.

  12. Docosahexaenoic acid supplementation early in pregnancy may prevent deep placentation disorders.

    PubMed

    Carvajal, Jorge A

    2014-01-01

    Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called "deep placentation disorders"; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

  13. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

    PubMed Central

    Carvajal, Jorge A.

    2014-01-01

    Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction. PMID:25019084

  14. Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term.

    PubMed

    Collier, Abby C; Thévenon, Audrey D; Goh, William; Hiraoka, Mark; Kendal-Wright, Claire E

    2015-12-01

    Placental UDP-glucuronosyltransferase (UGT) enzymes have critical roles in hormone, nutrient, chemical balance and fetal exposure during pregnancy. Placental UGT1A isoforms were profiled and differences between preeclamptic (PE) and non-PE placental UGT expression determined. In third trimester villous placenta, UGT1A1, 1A4, 1A6 and 1A9 were expressed and active in all specimens (n = 10), but UGT1A3, 1A5, 1A7, 1A8 and 1A10 were absent. The UGT1A activities were comparable to human liver microsomes per milligram, but placental microsome yields were only 2 % of liver (1 mg/g of tissue vs. 45 mg/g of tissue). For successful PCR, placental collection and processing within 60 min from delivery, including DNAse and ≥300 ng of RNA in reverse transcription were essential and snap freezing in liquid nitrogen immediately was the best preservation method. Although UGT1A6 mRNA was lower in PE (P < 0.001), there were no other significant effects on UGT mRNA, protein or activities. A more comprehensive tissue sample set is required for confirmation of PE interactions with UGT. Placental UGT1A enzyme expression patterns are similar to the liver and a detoxicative role for placental UGT1A is inferred.

  15. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.

  16. Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report.

    PubMed

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A; Hundt, Sophia; D'Alessio, Flavia; Sirima, Sodiomon B; Luty, Adrian J F; Duffy, Patrick; Leroy, Odile; Gamain, Benoit; Viebig, Nicola K

    2016-09-17

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines.

  17. Placental immunopathology and pregnancy failure in the FIV-infected cat.

    PubMed

    Weaver, C C; Burgess, S C; Nelson, P D; Wilkinson, M; Ryan, P L; Nail, C A; Kelly-Quagliana, K A; May, M L; Reeves, R K; Boyle, C R; Coats, K S

    2005-01-01

    Placental HIV infections frequently result in infected babies or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-infected cat is a model for HIV infections due to similarities in biology and clinical disease. The purpose of this study was to evaluate placental immunomodulator expression and reproductive outcome using the FIV-infected cat model. Kittens were cesarean delivered from FIV-B-2542-infected and control queens near term; placental and fetal tissues were collected. Real-time RT-PCR was used to measure expression of representative placental Th1 cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), a Th2 cytokine, IL-10, and chemokine receptor CXCR4. On average, control queens delivered 3.8 kittens/litter; 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter; 15 of 25 concepti (60%) were non-viable. FIV was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using PCR. Placental immunomodulator expression did not differ significantly when placentas from infected cats were compared to those of control cats. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions. Therefore, increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.

  18. Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term

    PubMed Central

    Thévenon, Audrey D.; Goh, William; Hiraoka, Mark; Kendal-Wright, Claire E.

    2014-01-01

    Placental UDP-glucuronosyltransferase (UGT) enzymes have critical roles in hormone, nutrient, chemical balance and fetal exposure during pregnancy. Placental UGT1A isoforms were profiled and differences between preeclamptic (PE) and non-PE placental UGT expression determined. In third trimester villous placenta, UGT1A1, 1A4, 1A6 and 1A9 were expressed and active in all specimens (n = 10), but UGT1A3, 1A5, 1A7, 1A8 and 1A10 were absent. The UGT1A activities were comparable to human liver microsomes per milligram, but placental microsome yields were only 2 % of liver (1 mg/g of tissue vs. 45 mg/g of tissue). For successful PCR, placental collection and processing within 60 min from delivery, including DNAse and ≥300 ng of RNA in reverse transcription were essential and snap freezing in liquid nitrogen immediately was the best preservation method. Although UGT1A6 mRNA was lower in PE (P < 0.001), there were no other significant effects on UGT mRNA, protein or activities. A more comprehensive tissue sample set is required for confirmation of PE interactions with UGT. Placental UGT1A enzyme expression patterns are similar to the liver and a detoxicative role for placental UGT1A is inferred. PMID:25465229

  19. The Uterine Placental Bed Renin-Angiotensin System in Normal and Preeclamptic Pregnancy

    PubMed Central

    Anton, Lauren; Merrill, David C.; Neves, Liomar A. A.; Diz, Debra I.; Corthorn, Jenny; Valdes, Gloria; Stovall, Kathryn; Gallagher, Patricia E.; Moorefield, Cheryl; Gruver, Courtney; Brosnihan, K. Bridget

    2009-01-01

    Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT1), AT2, and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT2 receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT1 receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia. PMID:19520788

  20. Maternal fructose drives placental uric acid production leading to adverse fetal outcomes.

    PubMed

    Asghar, Zeenat A; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L; Moley, Kelle H

    2016-04-29

    Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.

  1. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    PubMed Central

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-01-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions. PMID:3466175

  2. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    PubMed

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-12-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  3. The preterm placental microbiome varies in association with excess maternal gestational weight gain

    PubMed Central

    Antony, Kathleen M.; Ma, Jun; Mitchell, Kristen B.; Racusin, Diana A.; Versalovic, James; Aagaard, Kjersti

    2016-01-01

    OBJECTIVE Although a higher maternal body mass index is associated with preterm birth, it is unclear whether excess gestational weight gain (GWG) or obesity drives increased risk. We and others have shown that the placenta harbors microbiota, which is significantly different among preterm births. Our aim in this study was to investigate whether the preterm placental microbiome varies by virtue of obesity or alternately by excess GWG. STUDY DESIGN Placentas (n = 320) were collected from term and preterm pregnancies. Genomic DNA was extracted and subjected to metagenomic sequencing. Data were analyzed by clinical covariates that included the 2009 Institute of Medicine’s GWG guideline and obesity. RESULTS Analysis of 16S recombinant RNA–based metagenomics revealed no clustering of the microbiome by virtue of obesity (P = .161). Among women who spontaneously delivered preterm, there was again no clustering by obesity (P = .480), but there was significant clustering by excess GWG (P = .022). Moreover, among pretermbirths, detailed analysis identified microbial genera (family and genus level) and bacterial metabolic gene pathways that varied among pregnancies with excess GWG. Notably, excess GWG was associated with decreased microbial folate biosynthesis pathways and decreased butanoate metabolism (linear discriminate analysis, >3.0-fold). CONCLUSION Although there were no significant alterations in the microbiome by virtue of obesity per se, excess GWG was associated with an altered microbiome and its metabolic profile among those women who experienced a preterm birth. PMID:25557210

  4. Purification and properties of molecular-weight variants of human placental alkaline phosphatase

    PubMed Central

    Ghosh, Nimai K.; Fishman, William H.

    1968-01-01

    1. Alkaline phosphatase of human placenta was purified by a procedure involving homogenization with tris buffer, pH8·6, extraction with butanol, ammonium sulphate fractionation, exposure to heat, ethanol fractionation, gel filtration, triethylaminoethylcellulose anion-exchange chromatography, continuous curtain electrophoresis on paper and equilibrium dialysis. Methods for both laboratory-scale and large-scale preparation were devised. 2. Two major molecular-weight variants designated A and B were separated by molecular sieving with Sephadex G-200 and variant A was purified 4000-fold. 3. Variant B, which comes off the Sephadex G-200 column before variant A, is the electrophoretically slower-moving species on starch gel and is quite heterogeneous. 4. Purified variant A was fairly homogeneous on the basis of electrophoretic studies on starch gel and Sephadex gel, ultracentrifugation and immunodiffusion. 5. The respective molecular weights for variants A and B were 70000 and over 200000 on the basis of sucrose-density-gradient ultracentrifugation. Variant A exhibited a sedimentation coefficient of 4·2s. 6. Crystalline variant B could be converted into fast-moving variant A and vice versa. 7. Kinetic studies indicated no difference between the two variants. These include linear rates of hydrolysis, pH optimum, Michaelis constants and uncompetitive stereospecific l-phenylalanine inhibition. 8. The amino acid compositions of variants A and B and of placental albumin were determined. ImagesFig. 3.Fig. 5.Fig. 7.Fig. 8.Fig. 9. PMID:4970595

  5. The preterm placental microbiome varies in association with excess maternal gestational weight gain.

    PubMed

    Antony, Kathleen M; Ma, Jun; Mitchell, Kristen B; Racusin, Diana A; Versalovic, James; Aagaard, Kjersti

    2015-05-01

    Although a higher maternal body mass index is associated with preterm birth, it is unclear whether excess gestational weight gain (GWG) or obesity drives increased risk. We and others have shown that the placenta harbors microbiota, which is significantly different among preterm births. Our aim in this study was to investigate whether the preterm placental microbiome varies by virtue of obesity or alternately by excess GWG. Placentas (n=320) were collected from term and preterm pregnancies. Genomic DNA was extracted and subjected to metagenomic sequencing. Data were analyzed by clinical covariates that included the 2009 Institute of Medicine's GWG guideline and obesity. Analysis of 16S recombinant RNA-based metagenomics revealed no clustering of the microbiome by virtue of obesity (P=.161). Among women who spontaneously delivered preterm, there was again no clustering by obesity (P=.480), but there was significant clustering by excess GWG (P=.022). Moreover, among preterm births, detailed analysis identified microbial genera (family and genus level) and bacterial metabolic gene pathways that varied among pregnancies with excess GWG. Notably, excess GWG was associated with decreased microbial folate biosynthesis pathways and decreased butanoate metabolism (linear discriminate analysis, >3.0-fold). Although there were no significant alterations in the microbiome by virtue of obesity per se, excess GWG was associated with an altered microbiome and its metabolic profile among those women who experienced a preterm birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Matrotrophy and placentation in invertebrates: a new paradigm.

    PubMed

    Ostrovsky, Andrew N; Lidgard, Scott; Gordon, Dennis P; Schwaha, Thomas; Genikhovich, Grigory; Ereskovsky, Alexander V

    2016-08-01

    histophagy are rarer, plausibly evolving through heterochronous development of the embryonic mouthparts and digestive system. During gestation, matrotrophic modes can shift, intergrade, and be performed simultaneously. Invertebrate matrotrophic adaptations are less complex structurally than in chordates, but they are more diverse, being formed either by a parent, embryo, or both. In a broad and still preliminary sense, there are indications of trends or grades of evolutionarily increasing complexity of nutritive structures: formation of (i) local zones of enhanced nutritional transport (placental analogues), including specialized parent-offspring cell complexes and various appendages increasing the entire secreting and absorbing surfaces as well as the contact surface between embryo and parent, (ii) compartmentalization of the common incubatory space into more compact and 'isolated' chambers with presumably more effective nutritional relationships, and (iii) internal secretory ('milk') glands. Some placental analogues in onychophorans and arthropods mimic the simplest placental variants in vertebrates, comprising striking examples of convergent evolution acting at all levels-positional, structural and physiological.

  7. Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

    PubMed Central

    de Moura, R; Lopes, M A

    1995-01-01

    1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

  8. Heparan Sulfate Proteoglycans and Their Binding Proteins in Embryo Implantation and Placentation

    PubMed Central

    Kirn-Safran, Catherine; D’Souza, Sonia S.; Carson, Daniel D.

    2008-01-01

    Complex interactions occur among embryonic, placental and maternal tissues during embryo implantation. Many of these interactions are controlled by growth factors, extracellular matrix and cell surface components that share the ability to bind heparan sulfate (HS) polysaccharides. HS is carried by several classes of cell surface and secreted proteins called HS proteoglycan that are expressed in restricted patterns during implantation and placentation. This review will discuss the expression of HS proteoglycans and various HS binding growth factors as well as extracellular matrix components and HS-modifying enzymes that can release HS-bound proteins in the context of implantation and placentation. PMID:17766150

  9. The Human Placenta Project: placental structure, development, and function in real time.

    PubMed

    Guttmacher, A E; Maddox, Y T; Spong, C Y

    2014-05-01

    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time. Published by Elsevier Ltd.

  10. [Squamous cell carcinoma in situ of the cervix and placental site nodule: Case report].

    PubMed

    Gómez, María Constanza; Abaúnza, María Claudia; Vargas, Elga Johanna; Acosta, Inés

    2017-01-01

    An asymptomatic 24-year-old woman underwent a colposcopy, cervical biopsy, and subsequently, a conization for a cervical squamous cell carcinoma in situ with glandular extension. Simultaneously, an endometrial biopsy was carried out in which, incidentally, a placental site nodule was diagnosed, a rare non-neoplastic lesion originating in the intermediate trophoblast. Given the coexistence of these two entities, it was necessary to make a differential diagnosis between them and also with other pathologies of the trophoblast such as an exaggerated placental site, placental site trophoblastic tumor, and epithelioid trophoblastic tumor.

  11. A case of confined placental mosaicism with double trisomy associated with stillbirth.

    PubMed

    Goodfellow, L R; Batra, G; Hall, V; McHale, E; Heazell, A E P

    2011-09-01

    We present a case of stillbirth in which the fetus was well grown and karyotypically normal, but the placenta was morphologically abnormal and had confined placental mosaicism (CPM) for a double trisomy of chromosomes 12 and 15. A compilation of published cases of CPM reveals that whilst approximately 80% of pregnancies progress normally, there is an association with abnormal placental morphology, intrauterine growth restriction, fetal abnormalities and stillbirth. This case highlights the potential adverse effects of CPM and the benefit of placental examination in determining the cause of stillbirth.

  12. Schistosomiasis Japonica During Pregnancy Is Associated With Elevated Endotoxin Levels in Maternal and Placental Compartments

    PubMed Central

    McDonald, Emily A.; Pond-Tor, Sunthorn; Jarilla, Blanca; Sagliba, Marianne J.; Gonzal, Annaliza; Amoylen, Amabelle J.; Olveda, Remigio; Acosta, Luz; Gundogan, Fusun; Ganley-Leal, Lisa M.; Kurtis, Jonathan D.; Friedman, Jennifer F.

    2014-01-01

    Schistosomiasis affects approximately 40 million women of reproductive age and has been linked to elevated levels of circulating endotoxin in nonpregnant individuals. We have evaluated endotoxin levels in maternal, placental, and newborn blood collected from women residing in Leyte, Philippines. Endotoxin levels in both maternal and placental compartments in pregnant women with schistosomiasis were 1.3- and 2.4-fold higher, respectively, than in uninfected women. In addition, higher concentrations of endotoxin in placental blood were associated with premature birth, acute chorioamnionitis, and elevated proinflammatory cytokines. By promoting endotoxemia, schistosomiasis may exert additional, maladaptive influences on pregnancy outcomes. PMID:23964108

  13. Isolation of Propionibacterium acnes from a case of placentitis and abortion in a cow.

    PubMed

    Lyons, Jeremiah A; Bemis, David A; Bryant, Mary Jean; Kania, Stephen A; Abd-Eldaim, Mohamed; Newman, Shelley J

    2009-03-01

    On the basis of the scarcity of reports in the veterinary literature, it appears that Propionibacterium spp. are rarely associated with disease or isolated from cattle tissues. Recently, Propionibacterium spp. has been associated with multifocal abscessation in cattle. This report describes a case of necrosuppurative placentitis and abortion in an adult Holstein cow. Numerous colonies of small, pleomorphic, Gram-positive, rod-shaped bacteria were observed within the fibrin lattice associated with placental lesions and within the fetal atelectatic lung. Propionibacterium acnes was isolated in high numbers from the placenta, fetal lung, and stomach contents. To the authors' knowledge, this is the first report of placentitis associated with propionibacteria in a cow.

  14. Matrix Metalloproteinase-9 Polymorphism 1562 C > T (rs3918242) Associated with Protection against Placental Malaria

    PubMed Central

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash; Meese, Stefanie; Gai, Prabhanjan P.; Bedu-Addo, George; Mockenhaupt, Frank P.

    2015-01-01

    Phagocytosis of malaria pigment (hemozoin) induces increased activity of matrix metalloproteinase (MMP)-9, an endopeptidase involved in cytokine regulation. In this study, we examined whether a common functional MMP-9 promoter polymorphism (rs3918242) affects Plasmodium falciparum infection in pregnancy. Eighteen percent of Ghanaian primiparae carried the minor T allele. It was associated with reduced odds of placental hemozoin and of placental as well as peripheral blood parasitemia. The results indicate that a common MMP-9 polymorphism protects against placental malaria indicating that this endopeptidase is involved in susceptibility to P. falciparum. PMID:26013370

  15. Angiogenic proteins, placental weight and perinatal outcomes among pregnant women in Tanzania

    PubMed Central

    McDonald, Chloe R.; Darling, Anne M.; Liu, Enju; Tran, Vanessa; Cabrera, Ana; Aboud, Said; Urassa, Willy; Kain, Kevin C.; Fawzi, Wafaie W.

    2016-01-01

    Introduction Placental vascular development, and ultimately placental weight, is essential to healthy fetal development. Here, we examined placental weight in a cohort of Tanzanian women in association with angiogenic proteins known to regulate placental vascular development and perinatal outcomes. Methods A total of n = 6579 women with recorded placental weight were included in this study. The relative risk of adverse perinatal outcomes (Apgar score, death, asphyxia, respiratory distress, seizures, pneumonia and sepsis) was compared between placental weight in the bottom and top 10th percentiles. We quantified angiogenic mediators (Ang-1, Ang-2, VEGF, PGF and sFlt-1) in plasma samples (n = 901) collected between 12 to 27 weeks of pregnancy using ELISA and assessed the relative risk of placental weight in the bottom and top 10th percentiles by protein levels in quartiles. Results Women with Ang-2 levels in the highest quartile had an increased relative risk of placental weight in the bottom 10th percentile (RR = 1.45 (1.10, 1.91), p = 0.01). Women with VEGF-A (RR = 0.73 (0.56, 0.96), p = 0.05) and PGF (RR = 0.58 (0.44, 0.72), p = 0.002) in the highest quartile had a reduced relative risk of placental weight in the bottom 10th percentile. Low placental weight (in bottom 10th percentile) was associated with an increased relative risk of Apgar score of <7 at 1 minute (RR = 2.31 (1.70, 3.13), p = 0.001), at 5 minutes (RR = 3.53 (2.34, 5.33), p = 0.001), neonatal death (RR = 5.02 (3.61, 7.00), p = 0.001), respiratory distress (RR = 4.80(1.71, 13.45), p = 0.001), and seizures (RR = 4.18 (1.16, 15.02), p = 0.03). Discussion The association between low placental weight and risk of adverse perinatal outcomes in this cohort suggests that placental weight could serve as a useful indicator, providing additional insight into high-risk pregnancies and identifying neonates that may require additional monitoring and follow-up. PMID:27936130

  16. Screening and analyzing genes associated with Amur tiger placental development.

    PubMed

    Li, Q; Lu, T F; Liu, D; Hu, P F; Sun, B; Ma, J Z; Wang, W J; Wang, K F; Zhang, W X; Chen, J; Guan, W J; Ma, Y H; Zhang, M H

    2014-09-26

    The Amur tiger is a unique endangered species in the world, and thus, protection of its genetic resources is extremely important. In this study, an Amur tiger placenta cDNA library was constructed using the SMART cDNA Library Construction kit. A total of 508 colonies were sequenced, in which 205 (76%) genes were annotated and mapped to 74 KEGG pathways, including 29 metabolism, 29 genetic information processing, 4 environmental information processing, 7 cell motility, and 5 organismal system pathways. Additionally, PLAC8, PEG10 and IGF-II were identified after screening genes from the expressed sequence tags, and they were associated with placental development. These findings could lay the foundation for future functional genomic studies of the Amur tiger.

  17. Placental Epigenetics in Children’s Environmental Health

    PubMed Central

    Marsit, Carmen J.

    2016-01-01

    There is a growing interest in understanding the mechanisms that drive the developmental origins of health and disease, and the role of epigenetic regulation has risen to the forefront of these studies. In particular, the placenta may be a model organ to consider as a mediator of the impact of the environment on developmental programming of children’s health, as this organ plays a critical role in directing development and regulating the fetal environment. Several recent studies have begun to examine how environmental toxicant exposures can impact the placental epigenome, focusing on studies of DNA methylation and microRNA expression. This review highlights several of these studies and emphasizes the potential the placenta may hold on the broader understanding of the impact of the intrauterine environment on long-term health. PMID:26696277

  18. Abnormal Placentation: Placenta Previa, Vasa Previa, and Placenta Accreta.

    PubMed

    Silver, Robert M

    2015-09-01

    Placental disorders such as placenta previa, placenta accreta, and vasa previa are all associated with vaginal bleeding in the second half of pregnancy. They are also important causes of serious fetal and maternal morbidity and even mortality. Moreover, the rates of previa and accreta are increasing, probably as a result of increasing rates of cesarean delivery, maternal age, and assisted reproductive technology. The routine use of obstetric ultrasonography as well as improving ultrasonographic technology allows for the antenatal diagnosis of these conditions. In turn, antenatal diagnosis facilitates optimal obstetric management. This review emphasizes an evidence-based approach to the clinical management of pregnancies with these conditions as well as highlights important knowledge gaps.

  19. Villus packing density and lacunarity: Markers of placental efficiency?

    PubMed

    Shah, R G; Salafia, C M; Girardi, T; Merz, G S

    2016-12-01

    We evaluate, in routine H&E histology slides, villus quantity in a given area (villous packing density, VPD) and the pattern or "gappiness" of villous distribution (lacunarity), and test for correlations with a proxy for fetoplacental metabolic rate, β calculated as (ln (placental weight)/ln (birthweight)) from Kleiber's law [1]. Three ∼4.3 mm(2) images each were obtained from 88 term placentas. Ranges of VPD and lacunarity were each correlated with β (r = 0.31, p = 0.003, r = 0.23, p = 0.03 and respectively). The relationship between β and within-placenta variation in VPD and lacunarity highlights the need to study not merely the mean but the variance of villous geometries and spatial distributions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Placental calcification: ultrastructural and X-ray microanalytic studies

    SciTech Connect

    Varma, V.A.; Kim, K.M.

    1985-01-01

    Calcification is common in human placentas and is widely recognized as a normal part of maturation and aging of this organ. Eleven human placentas were studied by light and electron microscopy to elucidate the mechanism of placental calcification. Earliest mineral deposits were seen along the trophoblastic basement membrane of the chorionic villi undergoing fibrinoid degeneration. Transmission electron microscopic examination revealed crystalline deposits within small membrane-bound vesicles; the latter appear to be derived from degenerating cells and were particularly numerous within the basement membrane. X-ray microanalysis of these deposits revealed calcium and phosphorus peaks and the pattern of calcium hydroxyapatite was noted by electron diffraction. This pattern of calcification, i.e., precipitation of calcium hydroxyapatite in association with extracellular membrane bound vesicles, is similar to that seen in physiologic and pathologic calcifications of other tissues.

  1. Presentation of Placental Site Trophoblastic Tumor with Amenorrhea

    PubMed Central

    Behnamfar, Fariba; Rouholamin, Safoura; Esteki, Mahboubeh

    2017-01-01

    Placental site throphoblastic tumor (PSTT) is a rare manifestation of gestational trophoblastic neoplasia that may complicate any type of pregnancy. The disease is unique from other type, and is defined by slow growth, low human chorionic gonadotropin (hCG) serum levels, the late-onset metastatic potential, and most significantly, insensitivity to chemotherapy. We describe a case of a 31-year-old woman with prolonged amenorrhea and slightly elevated serum beta hCG (βhCG) level, referred for termination of abnormal pregnancy. During curettage, necrotic tissue was removed and severs vaginal bleeding was controlled with medical therapy. Histology examination showed neoplastic intermediate trophoblastic cells with invasion to the vessel wall compatible with PSTT. After that, hysterectomy was down and serum βhCG declined to undetectable level 2 weeks after surgery and was followed for 2 years without complication. PMID:28401076

  2. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    PubMed

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency.

  3. Engine and radiator: fetal and placental interactions for heat dissipation.

    PubMed

    Schröder, H J; Power, G G

    1997-03-01

    The 'engine' of fetal metabolism generates heat (3-4 W kg-1 in fetal sheep) which has to be dissipated to the maternal organism. Fetal heat may move through the amniotic/allantoic fluids to the uterine wall (conductive pathway; total conductance, 1.1 W degrees C-1 kg-1) and with the umbilical arterial blood flow (convective pathway) to the placenta. Because resistance to heat flow is larger than zero fetal temperature exceeds maternal temperature by about 0.5 degree C (0.3-1 degree C). Probably 85% of fetal heat is lost to the maternal organism through the placenta, which thus serves as the main 'radiator'. Placental heat conductivity appears to be extremely high and this may lead to impaired heat exchange (guinea-pig placenta). A computer simulation demonstrates that fetal temperature is essentially clamped to maternal temperature, and that fetal thermoregulatory efforts to gain thermal independence would be futile. Indeed, when the late gestational fetus in utero is challenged by cold stress, direct and indirect indicators of (non-shivering) thermogenesis (oxygen consumption, increase of plasma glycerol and free fatty acid levels) change only moderately. In prematurely delivered lambs, however, cold stress provokes summit metabolism and maximum heat production. Only when birth is imitated in utero (by cord clamping, external artificial lung ventilation and cooling) do thermogenic efforts approach levels typical of extra-uterine life. This suggests the presence of inhibitors of thermogenesis of placental origin, e.g. prostaglandins and adenosine. When the synthesis of prostaglandins is blocked by pretreatment with indomethacin, sheep fetuses react to intra-uterine cooling with vigorous thermogenic responses, which can be subdued by infusion of prostaglandin E2 (PGE2). Since the sheep placenta is known to produce sufficient amounts of PGE2, it seems that the placenta controls fetal thermogenic responses to some extent. This transforms the fetus into an ectothermic

  4. Vulnerability of primitive human placental trophoblast to Zika virus

    PubMed Central

    Sheridan, Megan A.; Yunusov, Dinar; Balaraman, Velmurugan; Alexenko, Andrei P.; Yabe, Shinichiro; Verjovski-Almeida, Sergio; Schust, Danny J.; Franz, Alexander W.; Ezashi, Toshihiko; Roberts, R. Michael

    2017-01-01

    Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction. PMID:28193876

  5. Vulnerability of primitive human placental trophoblast to Zika virus.

    PubMed

    Sheridan, Megan A; Yunusov, Dinar; Balaraman, Velmurugan; Alexenko, Andrei P; Yabe, Shinichiro; Verjovski-Almeida, Sergio; Schust, Danny J; Franz, Alexander W; Sadovsky, Yoel; Ezashi, Toshihiko; Roberts, R Michael

    2017-02-28

    Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKV(U)) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKV(C)). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction.

  6. Vesicular uptake of macromolecules by human placental amniotic epithelial cells.

    PubMed

    Sharshiner, Rita; Brace, Robert A; Cheung, Cecilia Y

    2017-09-01

    Studies in animal models have shown that unidirectional vesicular transport of amniotic fluid across the amnion plays a primary role in regulating amniotic fluid volume. Our objective was to explore vesicle type, vesicular uptake and intracellular distribution of vesicles in human amnion cells using high- and super-resolution fluorescence microscopy. Placental amnion was obtained at cesarean section and amnion cells were prepared and cultured. At 20%-50% confluence, the cells were incubated with fluorophore conjugated macromolecules for 1-30 min at 22 °C or 37 °C. Fluorophore labeled macromolecules were selected as markers of receptor-mediated caveolar and clathrin-coated vesicular uptake as well as non-specific endocytosis. After fluorophore treatment, the cells were fixed, imaged and vesicles counted using Imaris(®) software. Vesicular uptake displayed first order saturation kinetics with half saturation times averaging 1.3 min at 37 °C compared to 4.9 min at 22 °C, with non-specific endocytotic uptake being more rapid at both temperatures. There was extensive cell-to-cell variability in uptake rate. Under super-resolution microscopy, the pattern of intracellular spatial distribution was distinct for each macromolecule. Co-localization of fluorescently labeled macromolecules was very low at vesicular dimensions. In human placental amnion cells, 1) vesicular uptake of macromolecules is rapid, consistent with the concept that vesicular transcytosis across the amnion plays a role in the regulation of amniotic fluid volume; 2) uptake is temperature dependent and variable among individual cells; 3) the unique intracellular distributions suggest distinct functions for each vesicle type; 4) non-receptor mediated vesicular uptake may be a primary vesicular uptake mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Glucocorticoids enhance CD163 expression in placental Hofbauer cells.

    PubMed

    Tang, Zhonghua; Niven-Fairchild, Tracy; Tadesse, Serkalem; Norwitz, Errol R; Buhimschi, Catalin S; Buhimschi, Irina A; Guller, Seth

    2013-01-01

    Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate receptor-β (FR-β), markers of antiinflammatory M2 macrophages, were specifically expressed by primary cultures of HBCs immunopurified from human term placentas. GC receptor mRNA and protein levels were higher in HBCs compared with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas expression of FR-β and CD68 were largely unresponsive to GC treatment. DEX treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC function. The level of CD163 mRNA, but not FR-β or CD68 mRNA, was stimulated in placental explant cultures by DEX treatment, and increased CD163/FR-β and CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC administration was associated with increased CD163/FR-β and CD163/CD68 mRNA ratios in placentas from women with spontaneous preterm birth. In conclusion, in vitro studies indicated that GC treatment specifically up-regulated CD163 expression in HBCs and enhanced HBC function. In addition, the observed alterations in patterns of expression of macrophage marker genes associated with maternal GC administration suggest that HBCs are in vivo targets of GC action.

  8. Glucocorticoids Enhance CD163 Expression in Placental Hofbauer Cells

    PubMed Central

    Tang, Zhonghua; Niven-Fairchild, Tracy; Tadesse, Serkalem; Norwitz, Errol R.; Buhimschi, Catalin S.; Buhimschi, Irina A.

    2013-01-01

    Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate receptor-β (FR-β), markers of antiinflammatory M2 macrophages, were specifically expressed by primary cultures of HBCs immunopurified from human term placentas. GC receptor mRNA and protein levels were higher in HBCs compared with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas expression of FR-β and CD68 were largely unresponsive to GC treatment. DEX treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC function. The level of CD163 mRNA, but not FR-β or CD68 mRNA, was stimulated in placental explant cultures by DEX treatment, and increased CD163/FR-β and CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC administration was associated with increased CD163/FR-β and CD163/CD68 mRNA ratios in placentas from women with spontaneous preterm birth. In conclusion, in vitro studies indicated that GC treatment specifically up-regulated CD163 expression in HBCs and enhanced HBC function. In addition, the observed alterations in patterns of expression of macrophage marker genes associated with maternal GC administration suggest that HBCs are in vivo targets of GC action. PMID:23142809

  9. Endocrine, paracrine, and autocrine placental mediators in labor.

    PubMed

    Iliodromiti, Zoe; Antonakopoulos, Nikolaos; Sifakis, Stavros; Tsikouras, Panagiotis; Daniilidis, Angelos; Dafopoulos, Kostantinos; Botsis, Dimitrios; Vrachnis, Nikolaos

    2012-01-01

    Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.

  10. Placental diversity in malagasy tenrecs: placentation in shrew tenrecs (Microgale spp.), the mole-like rice tenrec (Oryzorictes hova) and the web-footed tenrec (Limnogale mergulus).

    PubMed

    Enders, A C; Blankenship, T N; Goodman, S M; Soarimalala, V; Carter, A M

    2007-07-01

    Placentation in tenrecs of the subfamily Oryzorictinae, family Tenrecidae, has not been described previously. The structure of the placenta of this group and especially of the genus Microgale was investigated to determine its similarity or dissimilarity to previously described placentas of the tenrec subfamilies Potamogalinae and Tenrecinae. Fifteen specimens of the genus Microgale ranging from an early yolk sac stage to near term were available for study. Placentation in Microgale was found to be different from other tenrecids in that there is an early simple lateral rather than central haemophagous region. In addition, a more villous portion of the placental disk forms before the formation of a more compact labyrinth. Although the definitive placenta is cellular haemomonochorial, it lacks the spongy zone found in the Tenrecinae. Neither does it resemble the endotheliochorial condition found in the Potamogalinae. Of the two genera of the subfamily Oryzorictinae represented by single specimens, the placenta of Limnogale resembled that of the Microgale but Oryzorictes had several differences including a lobulated placental disk. It is concluded that there is more variation in placentation both within the subfamily Oryzorictinae and within the family Tenrecidae than would ordinarily be expected.

  11. Increased placental XIAP and caspase 3 is associated with increased placental apoptosis in a baboon model of maternal nutrient reduction (MNR)

    PubMed Central

    Arroyo, Juan A; Li, Cun; Schlabritz-Loutsevitch, Natalia; McDonald, Tom; Nathanielsz, Peter; Galan, Henry L

    2010-01-01

    Objective Our objective was to determine signaling molecules and apoptosis rate in the term placenta of a baboon model of maternal nutrient reduction (MNR). Study Design Female baboons were fed ad libitum for controls (CTR; n=7) or 70% of CTR diet (MNR; n=6) from 30 to 165 days of gestation (dG) with necropsy at 165 dG. Placental tissues were collected, fixed for immunohistochemistry or snap frozen to measure ERK, AKT, JNK, XIAP and caspase 3. Placental villous apoptosis was determined by TUNEL and cytokeratin 18 cleavage. Results Compared to CTR, MNR placentas demonstrated: reduced placental weight (p<0.02), decreased p-ERK (p<0.04), increase placental villous apoptosis (p<0.001), increased villous cytokeratin 18 cleavage, increased XIAP protein (p<0.007) and increased active caspase 3 (p<0.02). Conclusion We conclude that placental apoptosis is increased in this baboon model of MNR at term and that the increase in XIAP may be a protective mechanism against this apoptosis. PMID:20599184

  12. Aromatization of 7 alpha-methyl-19-nortestosterone by human placental microsomes in vitro.

    PubMed

    LaMorte, A; Kumar, N; Bardin, C W; Sundaram, K

    1994-02-01

    Part of the biological effects of testosterone (T) are mediated by its enzymatic reduction to 5 alpha-dihydrotestosterone (DHT) or aromatization to estradiol (E2). 7 alpha-Methyl-19-nortestosterone (MENT) is a synthetic androgen that is considerably more potent than T. Previous studies have shown that MENT is not 5 alpha-reduced. The studies reported here were undertaken to determine whether MENT undergoes enzymatic aromatization in vitro. Human placental microsomes were used as the source of the aromatase. Radioactive or nonradioactive T or MENT was incubated with the microsomes in the presence of NADPH and the metabolites extracted out with ethyl ether. Following evaporation of ether, the residue was dissolved in benzene-petroleum ether and extracted with 0.4 N NaOH which selectively removes phenolic metabolites of the androgens. When either radioactive T or MENT was incubated with the aromatase in the presence of NADPH, there was a 20-fold increase in the amount of radioactivity extracted with NaOH. In contrast, if the incubation was carried out in the absence of NADPH or in the presence of R76713, an aromatase inhibitor, most of the radioactivity remained in the benzene-petroleum ether phase. To further identify the enzymatic reaction products, thin layer chromatography (TLC) was performed. The Rf value for MENT was 0.22 while that of the major reaction product was 0.34, which corresponded with the RF value of the estrogen, 7 alpha-methyl-estradiol (MeE2). This was further verified by using a second solvent system for the chromatographic separation. In an effort to ascertain whether the metabolites bind to estrogen receptors (ER), rat uterine cytosol was used. NaOH extracts of medium following incubation of nonradioactive MENT with microsomes showed competitive inhibition of [3H]E2 binding to rat uterine ER. Furthermore, after [3H]MENT was incubated with microsomes, the radioactive metabolite extracted in NaOH showed specific binding to the ER which could

  13. Good practices in collecting umbilical cord and placental blood.

    PubMed

    Lopes, Lauren Auer; Bernardino, Elizabeth; Crozeta, Karla; Guimarães, Paulo Ricardo Bittencourt

    2016-08-18

    to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1) verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2) definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r) and R(r). while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality. identificar fatores relacionados à qualidade das amostras do sangue de cordão umbilical e placentário e definir boas práticas para sua coleta em um banco público de sangue de cordão umbilical e placentário. pesquisa descritiva, abordagem quantitativa, realizada em um banco público de sangue de cordão umbilical e placentário, desenvolvida em duas etapas: 1) verificação dos fatores obstétricos, neonatais e operacionais, obtidos por coleta em instrumento próprio e observação não participante; 2) definição das boas práticas, por meio do agrupamento de não-conformidades observadas antes, durante e após a coleta do sangue. Os dados foram analisados por meio da estatística descritiva, utilizando-se dos softwares Statistica(r) e R(r). houve

  14. Placental Histopathologic Changes Associated with Subclinical Malaria Infection and Its Impact on the Fetal Environment

    PubMed Central

    Parekh, Falgunee K.; Davison, Billie B.; Gamboa, Dionicia; Hernandez, Jean; Branch, OraLee H.

    2010-01-01

    Microscopic examination of placental tissue can provide an accurate assessment of malaria infection during pregnancy. In this cross-sectional study of 193 women in Iquitos, Peru, 1.0% and 6.6% had parasites in the peripheral blood as detected by microscopy and polymerase chain reaction, respectively. However, 22% had placental malaria pigment indicating past, subclinical infections. Placental tissues with pigment from 24 cases were matched by gravidity and month of delivery to 24 controls and histopathologically examined. Cases had significantly higher number of monocytes in the intervillous space (44.7 versus 25.5; P = 0.012). Pigmented monocytes in fetal vessels were present in 33.3% of cases. This study demonstrated that subclinical malarial infection occurred frequently in pregnant women and is associated with increased presence of monocytes in the placenta. Pigmented monocytes in fetal vessels suggest parasites can breach the placental barrier and enter the fetal circulation. PMID:21036823

  15. Review: Parent-offspring conflict and the control of placental function.

    PubMed

    Moore, T

    2012-02-01

    Evolutionary genetic arguments suggest that pregnancy is not a fully cooperative engagement between the mother and embryo. Trivers' concept of parent-offspring conflict indicates that the mother and embryo will disagree over the level of maternal investment in the pregnancy. Therefore, selection will favour mechanisms encoded by maternal genes that limit resource transfer to the embryo and mechanisms encoded by embryonic genes that enhance such transfer. These antagonistic selection pressures may have influenced the evolution of many aspects of placental regulation and function, including genomic imprinting and placental hormone production. However, the mother and embryo are not expected to disagree over aspects of placental function that benefit both parties; for example, regulation of haemostasis or resistance to infections etc. Therefore, an understanding of the complex regulation of placental function must consider the multiple selection pressures acting on this organ. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Fetal maturity and morbidity as related to placental weight and secondary ossification

    PubMed Central

    Pryse-Davies, J.

    1975-01-01

    The problem of objectivity in histopathology is illustrated by an attempt to determine the normal range and significance of two observations, placental weight and secondary ossification, made in perinatal pathology. Neither offered a satisfactory estimation of fetal maturity. The placental weight provided little evidence of any primary placental dysfunction: the placenta was very small in association with only 50% of the very small infants and a very small placental fetal weight ratio was an infrequent finding of doubtful significance. A method of classifying relatively retarded and advanced secondary ossification was devised. Significant retardation was found in association with males, growth retardation, some malformations, and multiple births: significantly advanced ossification was found in anencephaly. PMID:1197178

  17. Rna-seq analysis of the functional compartments within the rat placentation site

    USDA-ARS?s Scientific Manuscript database

    The rat placentation site is distinctly organized into interacting zones, the so-called labyrinth, junctional, and metrial gland compartments. These zones house unique cell populations equipped to undertake myriad prescribed functions including transport, hormonal responses, and immune interactions....

  18. Glucosamine supplementation during late gestation alters placental development and increases litter size

    USDA-ARS?s Scientific Manuscript database

    Background: During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support ...

  19. Intrauterine Growth Restriction Associated with Hematologic Abnormalities: Probable Manifestations of Placental Mesenchymal Dysplasia

    PubMed Central

    Martinez-Payo, Cristina; Bernabeu, Rocio Alvarez; Villar, Isabel Salas; Goy, Enrique Iglesias

    2015-01-01

    Introduction Placental mesenchymal dysplasia is a rare vascular disease associated with intrauterine growth restriction, fetal demise as well as Beckwith–Wiedemann syndrome. Some neonates present hematologic abnormalities possibly related to consumptive coagulopathy and hemolytic anemia in the placental circulation. Case report We present a case of placental mesenchymal dysplasia in a fetus with intrauterine growth restriction and cerebellar hemorrhagic injury diagnosed in the 20th week of pregnancy. During 26th week, our patient had an intrauterine fetal demise in the context of gestational hypertension. We have detailed the ultrasound findings that made us suspect the presence of hematologic disorders during 20th week. Discussion We believe that the cerebellar hematoma could be the consequence of thrombocytopenia accompanied by anemia. If hemorrhagic damage during fetal life is found, above all associates with an anomalous placental appearance and with intrauterine growth restriction, PMD should be suspected along other etiologies. PMID:26495159

  20. Chromosomal Mosaicism in Human Feto-Placental Development: Implications for Prenatal Diagnosis

    PubMed Central

    Grati, Francesca Romana

    2014-01-01

    Chromosomal mosaicism is one of the primary interpretative issues in prenatal diagnosis. In this review, the mechanisms underlying feto-placental chromosomal mosaicism are presented. Based on the substantial retrospective diagnostic experience with chorionic villi samples (CVS) of a prenatal diagnosis laboratory the following items are discussed: (i) The frequency of the different types of mosaicism (confined placental, CPM, and true fetal mosaicisms, TFM); (ii) The risk of fetal confirmation after the detection of a mosaic in CVS stratified by chromosome abnormality and placental tissue involvement; (iii) The frequency of uniparental disomy for imprinted chromosomes associated with CPM; (iv) The incidence of false-positive and false-negative results in CVS samples analyzed by only (semi-)direct preparation or long term culture; and (v) The implications of the presence of a feto-placental mosaicism for microarray analysis of CVS and non-invasive prenatal screening (NIPS). PMID:26237479

  1. The effect of hyperventilation on maternal placental blood flow in pregnant rabbits.

    PubMed

    Leduc, B

    1972-09-01

    1. In anaesthetized pregnant rabbits near term, cardiac output and its distribution were measured by injection of isotope-labelled microspheres. Hypocapnia (mean arterial P(CO) (2) 18 mm Hg), induced by intermittent positive pressure hyperventilation, caused a 43% reduction in maternal placental blood flow, attributed mainly to vasoconstriction. Myometrial flow was not significantly changed.2. Moderate hypercapnia (mean arterial P(CO) (2) 46 mm Hg) caused no change in placental flow, compared with observations made while breathing air spontaneously (P(CO) (2) 31 mm Hg).3. Intravenous infusions of adrenaline or noradrenaline 1 mug/kg. min caused maternal placental vasoconstriction.4. During the especially warm summer of 1969, there was a mean 46% reduction in maternal placental blood flow in pregnant rabbits near term, breathing room air spontaneously with normal blood gas values and rectal temperatures. This was associated with an increase in the number of runts and dead foetuses.

  2. A comparative study of five laboratory tests for foeto-placental dysfunction in late pregnancy

    PubMed Central

    Watson, D.; Siddiqui, S. A.; Stafford, J. E. H.; Gibbard, S.; Hewitt, V.

    1973-01-01

    Five foeto-placental function tests were studied in parallel in normal and abnormal late pregnancies with a view to establishing which test or tests is most satisfactorily able to identify the mother whose foetus is in danger. A critical examination of the levels in blood serum of two enzymes, placental phosphatase isoenzyme and cystine aminopeptidase, the polypeptide hormone placental lactogen (chorionic somatomammotrophin), and the oestrogen oestriol-17β is described. A correlation was attempted beween clinical data and the results of the above laboratory analyses and also with the daily urine oestrogen output. The plasma and urine oestriol levels proved generally to be the more useful warning tests in late pregnancy, whilst the plasma cystine aminopeptidase was the least sensitive indicator of foeto-placental dysfunction. PMID:4349714

  3. Increased nerve fibers in placental bed myometrium in women with preeclampsia.

    PubMed

    Fan, Ruijia; Qiu, Lin; Huang, Xiufeng; Chen, Zhengyun; Xu, Hong; Zhou, Caiyun; Zhang, Xinmei

    2011-12-01

    Narrowing of the uterine spiral arterioles below the deciduomyometrial junction is 1 of the key pathophysiological changes in women with preeclampsia. The contribution of pelvic autonomic nerves to decidualization and impaired placentation in preeclampsia is not clear. Placental bed biopsies were obtained from 10 women with preeclampsia and 23 nornotensive women at caesarean section. We stained them with anti-S100 and CD34 antibodies to detect the presence of nerve fibers and blood vessels, respectively. We detected S100-immunoactive nerve fibers in the myometrium but not in the decidua in both groups of women. S100-immunoactive nerve fiber density in the placental bed myometrium was significantly increased in women with preeclampsia compared to normotensive women. There was no clear relationship between the densities of nerve fibers and CD34-positive blood vessels in these biopsies. These results suggest increased nerve fibers in the placental bed myometrium may play a role in the pathogenesis of the preeclampsia.

  4. Impact of cesarean section on placental transfusion and iron-related hematological indices in term neonates: a systematic review and meta-analysis.

    PubMed

    Zhou, Y-b; Li, H-t; Zhu, L-p; Liu, J-m

    2014-01-01

    Evidence suggests that cesarean section is likely associated with a reduced placental transfusion and poor hematological status in neonates. However, clinical studies have reported somewhat inconsistent results. We conducted a systematic review and meta-analysis to examine whether cesarean section affects placental transfusion and iron-related hematological indices. Pubmed, Web of Science, ScienceDirect, and Ovid Databases were searched for relevant studies published before April 9, 2013. Mean differences between cesarean section and vaginal delivery in outcomes of interests (placental residual blood volume; hematocrit level, hemoglobin concentration, and erythrocyte count in cord/peripheral blood) were extracted and pooled using a random effects model. We identified 15 studies (n = 8477) eligible for the meta-analysis. Compared with neonates born vaginally, those born by cesarean section had a higher placental residual blood volume [weighted mean difference (WMD), 8.87 ml; 95% confidence interval (CI), 2.32 ml-15.43 ml]; a lower level of hematocrit (WMD, -2.91%; 95% CI, -4.16% to -1.65%), hemoglobin (WMD, -0.51 g/dL; 95% CI, -0.74 g/dL to -0.27 g/dL) and erythrocyte (WMD, -0.16 × 10(12)/L; 95% CI, -0.30 × 10(12)/L to -0.01 × 10(12)/L). Subgroup analysis showed that the WMD for hematocrit in neonate's peripheral blood (-6.94%; 95% CI, -9.15% to -4.73%) was substantially lower than that in cord blood (-1.75%; 95% CI, -2.82%, -0.68%) (P value for testing subgroup differences <0.001). In conclusion, cesarean section compared with vaginal delivery is associated with a reduced placental transfusion and poor iron-related hematologic indices in both cord and peripheral blood, indicating that neonates delivered by cesarean section might be more likely affected by iron-deficiency anemia in infancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Feto- and utero-placental vascular adaptations to chronic maternal hypoxia in the mouse.

    PubMed

    Cahill, Lindsay S; Rennie, Monique Y; Hoggarth, Johnathan; Yu, Lisa X; Rahman, Anum; Kingdom, John C; Seed, Mike; Macgowan, Christopher K; Sled, John G

    2017-09-01

    Chronic fetal hypoxia is one of the most common complications of pregnancy and is known to cause fetal growth restriction. The structural adaptations of the placental vasculature responsible for growth restriction with chronic hypoxia are not well elucidated. Using a mouse model of chronic maternal hypoxia in combination with micro-computed tomography and scanning electron microscopy, we found several placental adaptations that were beneficial to fetal growth including capillary expansion, thinning of the interhaemal membrane and increased radial artery diameters, resulting in a large drop in total utero-placental vascular resistance. One of the mechanisms used to achieve the rapid increase in capillaries was intussusceptive angiogenesis, a strategy used in human placental development to form terminal gas-exchanging villi. These results contribute to our understanding of the structural mechanisms of the placental vasculature responsible for fetal growth restriction and provide a baseline for understanding adaptive physiological responses of the placenta to chronic hypoxia. The fetus and the placenta in eutherian mammals have a unique set of compensatory mechanisms to respond to several pregnancy complications including chronic maternal hypoxia. This study examined the structural adaptations of the feto- and utero-placental vasculature in an experimental mouse model of chronic maternal hypoxia (11% O2 from embryonic day (E) 14.5-E17.5). While placental weights were unaffected by exposure to chronic hypoxia, using micro-computed tomography, we found a 44% decrease in the absolute feto-placental arterial vascular volume and a 30% decrease in total vessel segments in the chronic hypoxia group compared to control group. Scanning electron microscopy imaging showed significant expansion of the capillary network; consequently, the interhaemal membrane was 11% thinner to facilitate maternal-fetal exchange in the chronic hypoxia placentas. One of the mechanisms for the rapid

  6. [Ebstein's anomaly revealed by fetal-placental anasarca. Original case study].

    PubMed

    Hadraoui, Hanaa El; Barkat, Amina

    2016-01-01

    Ebstein's anomaly is a congenital heart defect rarely revealed by fetal-placental anasarca. Our study reports an original case of Ebstein's anomaly diagnosed during fetal-placental anasarca assessment, revealed by antenatal ultrasound, objectifying hydramnios, ascites and pericardial effusion. Echocardiography allowed the identification of Ebstein's disease with significant tricuspid insufficiency, mitral regurgitation (grade 3) and patent ductus arteriosus. The closure of the ductus arteriosus associated with the decrease of pulmonary resistance using optimal ventilation allowed hemodynamic improvement and patient survival.

  7. CD74-downregulation of placental macrophage-trophoblastic interactions in preeclampsia

    PubMed Central

    Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Rugor, Julianna; Solano, Maria Emilia; Arck, Petra Clara; Gauster, Martin; Huppertz, Berthold; Emontzpohl, Christoph; Stoppe, Christian; Bernhagen, Jürgen; Leng, Lin; Bucala, Richard; Schulz, Herbert; Heuser, Arnd; Weedon-Fekjær, M. Susanne; Johnsen, Guro M.; Peetz, Dirk; Luft, Friedrich C; Staff, Anne Cathrine; Müller, Dominik N; Dechend, Ralf; Herse, Florian

    2017-01-01

    RATIONALE We hypothesized that Cluster of differentiation 74 (CD74) downregulation of placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. OBJECTIVE Preeclamptic pregnancies feature hypertension, proteinuria and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. METHODS AND RESULTS We performed whole genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By RT-PCR, we confirmed this finding in early onset (<34 gestational week, n=26) and late onset (≥34 gestational week, n=24) samples from preeclamptic women, compared to healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared to controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naïve and activated macrophages lacking CD74 showed a shift towards a pro-inflammatory signature with an increased secretion of TNFα, CCL5, and MCP-1, when co-cultured with trophoblasts compared to control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas and impaired spiral artery remodeling with fetal growth restriction. CONCLUSIONS CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts. PMID:27199465

  8. Magnetic Resonance Imaging and Sonography in the Diagnosis of Placental Invasion.

    PubMed

    Balcacer, Patricia; Pahade, Jay; Spektor, Michael; Staib, Lawrence; Copel, Joshua A; McCarthy, Shirley

    2016-07-01

    To compare older and newer magnetic resonance imaging (MRI) criteria for placental invasion and to compare the sensitivity, specificity, and accuracy of MRI and sonography in determining the depth of placental invasion. Forty pregnant patients at high risk for morbidly adherent placenta based on prenatal sonography underwent MRI evaluations. Two reviewers, who were blinded to the original MRI and sonographic interpretations, clinical history, and obstetric/pathologic findings, reviewed the MRI examinations. The MRI and sonographic scans were analyzed for the presence and depth of invasion. The MRI scans were tabulated for the presence of dark intraplacental T2 bands, bulging of the myometrium, increased vascularity, and indistinct myometrium, loss of the dark T2 myometrial/placental interface, and a thin myometrium. The obstetric/pathologic results served as the reference standards. Eighteen of 40 patients had a morbidly invasive placenta. The sensitivity, specificity, and accuracy of MRI and sonography were not significantly different. The accuracy rates for determining the depth of placental invasion by readers 1 and 2 were 0.65 and 0.55, respectively (P > .05). According to the Cohen κ statistic, there was a good inter-reader agreement between the MRI readers in assessing the depth of placental invasion (κ = 0.45). The features most commonly seen were dark T2 bands, bulging of the uterus, and loss of the dark T2 interface, which were all associated with the presence of placental invasion. The diagnosis of placental invasion remains challenging on sonography and MRI, which perform similarly. The presence of 2 or more criteria adds specificity to the diagnosis of placental invasion on MRI.

  9. Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary.

    PubMed

    Liu, Liang; Zhang, Jin; Rheindt, Frank E; Lei, Fumin; Qu, Yanhua; Wang, Yu; Zhang, Yu; Sullivan, Corwin; Nie, Wenhui; Wang, Jinhuan; Yang, Fengtang; Chen, Jinping; Edwards, Scott V; Meng, Jin; Wu, Shaoyuan

    2017-08-29

    The timing of the diversification of placental mammals relative to the Cretaceous-Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms.

  10. Virus-Free Human Placental Cell Lines To Study Genetic Functions | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.

  11. Effects of lymphokines and immune complexes on murine placental cell growth in vitro

    SciTech Connect

    Armstrong, D.T.; Chaouat, G. )

    1989-03-01

    Isolated murine placental cells obtained at Day 16 of allogeneic gestation (C3H x DBA/2J) were cultured for 3 days alone or in coculture with irradiated mouse splenocytes at the end of which 3H-thymidine was added for an additional 18-h culture to assess cell proliferation. Placental cell proliferation was significantly enhanced at spleen cell:placental cell ratios of 10:1 and 25:1 above that observed in the absence of added spleen cells. The stimulatory effect of irradiated allogeneic (C3H plus Balb/cJ) spleen cell cultures was significantly greater (approximately 2-fold) than that of isogeneic spleen cells (C3H alone). Conditioned medium from murine spleen cells cultured with concanavalin A (ConA) to induce lymphokine production had dose-dependent inhibitory effects on proliferation when added to placental cell cultures over a range of concentrations from 10 to 40% (vol:vol). Addition of pseudo immune complexes in the form of heat-aggregated human gamma globulin (AHGG) to culture medium failed to alter placental cell proliferation over a range of concentrations from 2 to 200 micrograms/ml either in the absence or presence of ConA-conditioned medium. In contrast to late-gestational stage placental cells, cell suspensions obtained from Days 8-9 murine ectoplacental cone (EPC) outgrowths, or from earlier stage placentas (Days 12-14) responded to low concentrations of conditioned medium from ConA-stimulated splenocytes with increased proliferation. The effect was less impressive on placental cells at gestational ages later than 12 days than on earlier stage preparations. On all placental cell suspensions tested, as well as EPC cells, a clear-cut inhibition of growth was observed at high doses of conditioned medium.

  12. Viscosity and haemodynamics in a late gestation rat feto-placental arterial network.

    PubMed

    Bappoo, Nikhilesh; Kelsey, Lachlan J; Parker, Louis; Crough, Tim; Moran, Carmel M; Thomson, Adrian; Holmes, Megan C; Wyrwoll, Caitlin S; Doyle, Barry J

    2017-08-01

    The placenta is a transient organ which develops during pregnancy to provide haemotrophic support for healthy fetal growth and development. Fundamental to its function is the healthy development of vascular trees in the feto-placental arterial network. Despite the strong association of haemodynamics with vascular remodelling mechanisms, there is a lack of computational haemodynamic data that may improve our understanding of feto-placental physiology. The aim of this work was to create a comprehensive 3D computational fluid dynamics model of a substructure of the rat feto-placental arterial network and investigate the influence of viscosity on wall shear stress (WSS). Late gestation rat feto-placental arteries were perfused with radiopaque Microfil and scanned via micro-computed tomography to capture the feto-placental arterial geometry in 3D. A detailed description of rat fetal blood viscosity parameters was developed, and three different approaches to feto-placental haemodynamics were simulated in 3D using the finite volume method: Newtonian model, non-Newtonian Carreau-Yasuda model and Fåhræus-Lindqvist effect model. Significant variability in WSS was observed between different viscosity models. The physiologically-realistic simulations using the Fåhræus-Lindqvist effect and rat fetal blood estimates of viscosity revealed detailed patterns of WSS throughout the arterial network. We found WSS gradients at bifurcation regions, which may contribute to vessel enlargement, and sprouting and pruning during angiogenesis. This simulation of feto-placental haemodynamics shows the heterogeneous WSS distribution throughout the network and demonstrates the ability to determine physiologically-relevant WSS magnitudes, patterns and gradients. This model will help advance our understanding of vascular physiology and remodelling in the feto-placental network.

  13. The role of non-placental signals in the adaptation of islets to pregnancy.

    PubMed

    Drynda, R; Peters, C J; Jones, P M; Bowe, J E

    2015-01-01

    It is well established that the maternal β-cell mass increases during pregnancy in both humans and rodents to compensate insulin resistance and increased metabolic demand, and rapidly returns to normal levels post-partum. However, the mechanisms underlying this adaptation are not well understood. It is established that this process is driven partly by placental signals, but the contribution of non-placental signals is still unclear. This study aimed to differentiate between the role of placental and non-placental signals in regulating the β-cell mass and glucose homeostasis during and after pregnancy. Pseudopregnant, pregnant and lactating mice were used to study the effects of maternal hormones on β-cell function during early pregnancy, mid-to-late pregnancy and post-partum, respectively. Pseudopregnant mice, with circulating hormone levels mirroring those during pregnancy but lacking placental signals, had significantly increased β-cell proliferation compared to non-pregnant controls but no change in glucose homeostasis, suggesting a role for non-placental hormones in increasing β-cell mass. The rate of β-cell proliferation rate dropped immediately after parturition, but lactating mice still had a significantly higher rate of β-cell proliferation compared to non-lactating post-partum mice, suggesting that lactation-related hormones play a role in the controlled involution of β-cell mass post-partum. These results implicate a role for both non-placental and placental signals in regulating β-cell mass during and after pregnancy. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

    PubMed

    Shiota, K; Furuyama, N; Takahashi, M

    1991-10-01

    The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. The Interrelationships of Placental Mammals and the Limits of Phylogenetic Inference.

    PubMed

    Tarver, James E; Dos Reis, Mario; Mirarab, Siavash; Moran, Raymond J; Parker, Sean; O'Reilly, Joseph E; King, Benjamin L; O'Connell, Mary J; Asher, Robert J; Warnow, Tandy; Peterson, Kevin J; Donoghue, Philip C J; Pisani, Davide

    2016-01-05

    Placental mammals comprise three principal clades: Afrotheria (e.g., elephants and tenrecs), Xenarthra (e.g., armadillos and sloths), and Boreoeutheria (all other placental mammals), the relationships among which are the subject of controversy and a touchstone for debate on the limits of phylogenetic inference. Previous analyses have found support for all three hypotheses, leading some to conclude that this phylogenetic problem might be impossible to resolve due to the compounded effects of incomplete lineage sorting (ILS) and a rapid radiation. Here we show, using a genome scale nucleotide data set, microRNAs, and the reanalysis of the three largest previously published amino acid data sets, that the root of Placentalia lies between Atlantogenata and Boreoeutheria. Although we found evidence for ILS in early placental evolution, we are able to reject previous conclusions that the placental root is a hard polytomy that cannot be resolved. Reanalyses of previous data sets recover Atlantogenata + Boreoeutheria and show that contradictory results are a consequence of poorly fitting evolutionary models; instead, when the evolutionary process is better-modeled, all data sets converge on Atlantogenata. Our Bayesian molecular clock analysis estimates that marsupials diverged from placentals 157-170 Ma, crown Placentalia diverged 86-100 Ma, and crown Atlantogenata diverged 84-97 Ma. Our results are compatible with placental diversification being driven by dispersal rather than vicariance mechanisms, postdating early phases in the protracted opening of the Atlantic Ocean.

  16. Benzopyrene and Experimental Stressors Cause Compensatory Differentiation in Placental Trophoblast Stem Cells

    PubMed Central

    Rappolee, Daniel A.; Awonuga, Awoniyi O.; Puscheck, Elizabeth E.; Zhou, Sichang; Xie, Yufen

    2013-01-01

    Stress causes decreased cell accumulation in early periimplantation embryos and the placental trophoblast stem cells derived from them. Benzopyrene and many other stressors activate stress enzymes that lead to suppressed stem cell accumulation through diminished proliferation and increased apoptosis. Trophoblast stem cells proliferate and a subpopulation of early postimplantation trophoblast cells differentiate to produce the first placental hormones that arise in the implanting conceptus. These hormones mediate antiluteolytic effects that enable the continuation of a successful implantation. The normal determination and differentiation of placental trophoblast stem cells is dependent upon a series of transcription factors. But, these transcription factors can also be modulated by stress through the activity of stress enzymes. This review enumerates and analyzes recent reports on the effects of benzopyrene on placental function in terms of the emerging paradigm that placental differentiation from stem cells can be regulated when insufficient production of stem cells is caused by stress. In addition, we review the other effects caused by benzopyrene throughout placental development. PMID:20377314

  17. Diagnostic test characteristics of placental weight in the prediction of small-for-gestational-age neonates.

    PubMed

    Ness, Roberta B; Bass, Debra; Hill, Lyndon; Klebanoff, Mark A; Zhang, Jun

    2007-09-01

    To assess the diagnostic test characteristics of placental weight as a clinical predictor of small-for-gestational-age (SGA) neonates. Placentas were weighed at 45,846 deliveries. Predictive values and likelihood ratios (LRs) were calculated assessing placental weight (lowest tertile vs. top 2 or mid/high tertiles) as a predictor of SGA both overall and by maternal age, gestational age, maternal weight, reported early pregnancy smoking, race, neonatal sex and parity. Although the positive predictive value (PPV) of low placental weight was poor (0.19), the negative predictive value (NPV) was high (0.97). Both NPV and LR- were powerfully predictive in women at earlier gestational ages. At gestational ages <32 weeks, LR-was 0.11, showing that among women with mid/high placental weight, the proportion with SGA (false negative) was about 1/10 that without SGA (true negative). Placental weight in the mid or upper tertile has strong NPV and LR- for delivery of an SGA neonate. Further study of the value of placental size in prediction of SGA is warranted.

  18. Investigation of biological factors influencing the placental mRNA profile in maternal plasma.

    PubMed

    Tsui, Nancy B Y; Wong, Cesar S C; Chow, Katherine C K; Lo, Elena S F; Cheng, Yvonne K Y

    2014-03-01

    Circulating placental-derived RNA is useful for noninvasive prenatal investigation. However, in addition to placental gene expression, there are limited investigations on other biological parameters that may affect the circulating placental RNA profile. In this study, we explored two of these potential parameters. We first demonstrated the existence of such biological parameters by comparing the relative levels of a panel of placental-derived transcripts between the placentas and maternal plasma by digital PCRs. We then compared the post-delivery clearance of the transcripts by serial plasma samples collected from pregnant women after delivery. We also studied the placental in vivo localization of the transcripts by in situ hybridization. There was an imperfect correlation of the transcript levels between the placentas and maternal plasma, with placenta-specific 4 (PLAC4) mRNA showing the largest discrepancy. Although PLAC4 mRNA showed a similar clearance half-life with other transcripts, we observed a preferential localization of PLAC4 mRNA around the villous surface. We speculated that this phenomenon might play a role in favoring the release of PLAC4 mRNA molecules into maternal plasma. We revealed that in addition to expression levels in the placenta, other biological factors might interplay to determine the maternal plasma profile of placental-derived RNAs. © 2013 John Wiley & Sons, Ltd.

  19. Assisted reproduction causes placental maldevelopment and dysfunction linked to reduced fetal weight in mice

    PubMed Central

    Chen, Shuqiang; Sun, Fang-zhen; Huang, Xiuying; Wang, Xiaohong; Tang, Na; Zhu, Baoyi; Li, Bo

    2015-01-01

    Compelling evidence indicates that stress in utero, as manifested by low birth weight (LBW), increases the risk of metabolic syndrome in adulthood. Singletons conceived by assisted reproductive technology (ART) display a significant increase in LBW risk and ART offspring have a different metabolic profile starting at birth. Here, used mouse as a model, we found that ART resulted in reduced fetal weight and placental overgrowth at embryonic day 18.5 (E18.5). The ART placentae exhibited histomorphological alterations with defects in placental layer segregation and glycogen cells migration at E18.5. Further, ART treatments resulted in downregulation of a majority of placental nutrient transporters and reduction in placental efficiency. Moreover, the ART placentae were associated with increased methylation levels at imprinting control regions of H19, KvDMR1 and disrupted expression of a majority of imprinted genes important for placental development and function at E18.5. Our results from the mouse model show the first piece of evidence that ART treatment could affect fetal growth by disrupting placental development and function, suggests that perturbation of genomic imprinting resulted from embryo manipulation may contribute to these problems. PMID:26085229

  20. Placental Hypomethylation Is More Pronounced in Genomic Loci Devoid of Retroelements

    PubMed Central

    Chatterjee, Aniruddha; Macaulay, Erin C.; Rodger, Euan J.; Stockwell, Peter A.; Parry, Matthew F.; Roberts, Hester E.; Slatter, Tania L.; Hung, Noelyn A.; Devenish, Celia J.; Morison, Ian M.

    2016-01-01

    The human placenta is hypomethylated compared to somatic tissues. However, the degree and specificity of placental hypomethylation across the genome is unclear. We assessed genome-wide methylation of the human placenta and compared it to that of the neutrophil, a representative homogeneous somatic cell. We observed global hypomethylation in placenta (relative reduction of 22%) compared to neutrophils. Placental hypomethylation was pronounced in intergenic regions and gene bodies, while the unmethylated state of the promoter remained conserved in both tissues. For every class of repeat elements, the placenta showed lower methylation but the degree of hypomethylation differed substantially between these classes. However, some retroelements, especially the evolutionarily younger Alu elements, retained high levels of placental methylation. Surprisingly, nonretrotransposon-containing sequences showed a greater degree of placental hypomethylation than retrotransposons in every genomic element (intergenic, introns, and exons) except promoters. The differentially methylated fragments (DMFs) in placenta and neutrophils were enriched in gene-poor and CpG-poor regions. The placentally hypomethylated DMFs were enriched in genomic regions that are usually inactive, whereas hypermethylated DMFs were enriched in active regions. Hypomethylation of the human placenta is not specific to retroelements, indicating that the evolutionary advantages of placental hypomethylation go beyond those provided by expression of retrotransposons and retrogenes. PMID:27172225

  1. Assessment of Placental Stiffness Using Acoustic Radiation Force Impulse Elastography in Pregnant Women with Fetal Anomalies

    PubMed Central

    Göya, Cemil; Tunç, Senem; Teke, Memik; Hattapoğlu, Salih

    2016-01-01

    Objective We aimed to evaluate placental stiffness measured by acoustic radiation force impulse (ARFI) elastography in pregnant women in the second trimester with a normal fetus versus those with structural anomalies and non-structural findings. Materials and Methods Forty pregnant women carrying a fetus with structural anomalies diagnosed sonographically at 18–28 weeks of gestation comprised the study group. The control group consisted of 34 healthy pregnant women with a sonographically normal fetus at a similar gestational age. Placental shear wave velocity (SWV) was measured by ARFI elastography and compared between the two groups. Structural anomalies and non-structural findings were scored based on sonographic markers. Placental stiffness measurements were compared among fetus anomaly categories. Doppler parameters of umbilical and uterine arteries were compared with placental SWV measurements. Results All placental SWV measurements, including minimum SWV, maximum SWV, and mean SWV were significantly higher in the study group than the control group ([0.86 ± 0.2, 0.74 ± 0.1; p < 0.001], [1.89 ± 0.7, 1.59 ± 0.5; p = 0.04], and [1.26 ± 0.4, 1.09 ± 0.2; p = 0.01]), respectively. Conclusion Placental stiffness evaluated by ARFI elastography during the second trimester in pregnant women with fetuses with congenital structural anomalies is higher than that of pregnant women with normal fetuses. PMID:26957906

  2. The Interrelationships of Placental Mammals and the Limits of Phylogenetic Inference

    PubMed Central

    Tarver, James E.; dos Reis, Mario; Mirarab, Siavash; Moran, Raymond J.; Parker, Sean; O’Reilly, Joseph E.; King, Benjamin L.; O’Connell, Mary J.; Asher, Robert J.; Warnow, Tandy; Peterson, Kevin J.; Donoghue, Philip C.J.; Pisani, Davide

    2016-01-01

    Placental mammals comprise three principal clades: Afrotheria (e.g., elephants and tenrecs), Xenarthra (e.g., armadillos and sloths), and Boreoeutheria (all other placental mammals), the relationships among which are the subject of controversy and a touchstone for debate on the limits of phylogenetic inference. Previous analyses have found support for all three hypotheses, leading some to conclude that this phylogenetic problem might be impossible to resolve due to the compounded effects of incomplete lineage sorting (ILS) and a rapid radiation. Here we show, using a genome scale nucleotide data set, microRNAs, and the reanalysis of the three largest previously published amino acid data sets, that the root of Placentalia lies between Atlantogenata and Boreoeutheria. Although we found evidence for ILS in early placental evolution, we are able to reject previous conclusions that the placental root is a hard polytomy that cannot be resolved. Reanalyses of previous data sets recover Atlantogenata + Boreoeutheria and show that contradictory results are a consequence of poorly fitting evolutionary models; instead, when the evolutionary process is better-modeled, all data sets converge on Atlantogenata. Our Bayesian molecular clock analysis estimates that marsupials diverged from placentals 157–170 Ma, crown Placentalia diverged 86–100 Ma, and crown Atlantogenata diverged 84–97 Ma. Our results are compatible with placental diversification being driven by dispersal rather than vicariance mechanisms, postdating early phases in the protracted opening of the Atlantic Ocean. PMID:26733575

  3. Lipid Raft- and Src Family Kinase-Dependent Entry of Coxsackievirus B into Human Placental Trophoblasts

    PubMed Central

    Delorme-Axford, Elizabeth; Sadovsky, Yoel

    2013-01-01

    Maternal-fetal transmission of group B coxsackieviruses (CVB) during pregnancy has been associated with a number of diverse pathological outcomes, including hydrops fetalis, fetal myocarditis, meningoencephalitis, neurodevelopmental delays, congenital skin lesions, miscarriage, and/or stillbirth. Throughout pregnancy, the placenta forms a critical antimicrobial protective barrier at the maternal-fetal interface. Despite the severity of diseases accompanying fetal CVB infections, little is known regarding the strategies used by CVB to gain entry into placental trophoblasts. Here we used both a trophoblast cell line and primary human trophoblasts to demonstrate the mechanism by which CVB gains entry into polarized placental trophoblasts. Our studies revealed that the kinetics of CVB entry into placental trophoblasts are similar to those previously described for polarized intestinal epithelial cells. Likewise, CVB entry into placental trophoblasts requires decay-accelerating factor (DAF) binding and involves relocalization of the virus from the apical surface to intercellular tight junctions. In contrast, we have identified a divergent mechanism for CVB entry into polarized trophoblasts that is clathrin, caveolin-1, and dynamin II independent but requires intact lipid rafts. In addition, we found that members of the Src family of tyrosine kinases were required for CVB entry. Our studies highlight the complexity of viral entry into human placental trophoblasts and may serve as a model for mechanisms used by diverse pathogens to penetrate the placental barrier. PMID:23720726

  4. Fetal signaling through placental structure and endocrine function: illustrations and implications from a nonhuman primate model.

    PubMed

    Rutherford, Julienne N

    2009-01-01

    The placenta is a transmitter of fetal need and fetal quality, interfacing directly with maternal physiology and ecology. Plasticity of placental structure and function across the developmental timeframe of gestation may serve as an important tool by which a fetus calibrates its growth to shifting maternal ecology and resource availability, and thereby signals its quality and adaptability to a changing environment. Signals of this quality may be conveyed by the size of the placental interface, an important marker of fetal access to maternal resources, or by production of placental insulin-like growth factor-II, a driver of fetoplacental growth. Litter size variation in the common marmoset monkey offers the opportunity to explore intrauterine resource allocation and placental plasticity in an important nonhuman primate model. Triplet marmosets are born at lower birth weights and have poorer postnatal outcomes and survivorship than do twins; triplet placentas differ in placental efficiency, microscopic morphology, and endocrine function. Through placental plasticity, triplet fetuses are able to adjust functional access to maternal resources in a way that allows pregnancy to proceed. However, the costs of such mechanisms may relate to reduced fetal growth and altered postnatal outcomes, with the potential to lead to adverse adult health consequences, suggesting an important link between the placenta itself and the developmental origins of health and disease.

  5. Exposure of pregnant mice to triclosan impairs placental development and nutrient transport

    PubMed Central

    Cao, Xinyuan; Hua, Xu; Wang, Xiaoli; Chen, Ling

    2017-01-01

    Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6–18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight. PMID:28322267

  6. Placental sharing, birthweight discordance, and vascular anastomoses in monochorionic diamniotic twin placentas.

    PubMed

    Lewi, Liesbeth; Cannie, Mieke; Blickstein, Isaac; Jani, Jacques; Huber, Agnes; Hecher, Kurt; Dymarkowski, Steven; Gratacós, Eduard; Lewi, Paul; Deprest, Jan

    2007-12-01

    The purpose of this study was to examine the relationship between placental territory and birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas from pregnancies that were not complicated by twin-to-twin transfusion syndrome with 2 liveborn twins. Placentas originated from a prospective follow-up study of monochorionic diamniotic twins included in the first trimester. After injection with dyed barium sulphate, a digital x-ray angiography and high-resolution digital photograph were taken. The 2 venous territories were delineated on the angiogram. The diameter of each arterioarterial anastomosis and of each vein that participated in an arteriovenous anastomosis was measured on the digital photograph. Net transfusion over the arteriovenous anastomoses was calculated as the difference between the total venous diameters of the 2 placental parts. One hundred placentas were analyzed. Birthweight discordance increased with placental territory discordance (P < .0001). Arterioarterial diameter (P < .01), net arteriovenous transfusion (P < .001), and total anastomotic diameter (P < .01) increased with placental territory discordance. On the other hand, birthweight discordance for a given placental territory discordance decreased with increasing arterioarterial diameter (P < .01), net arteriovenous transfusion (P < .001), and total anastomotic diameter (P < .01). In unequally shared placentas, the 2 fetal circulations are more tightly linked than in equally shared placentas, which may reduce the birthweight discordance for a given placental territory discordance.

  7. Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling

    SciTech Connect

    Peng Sha; Miao Chenglin; Li Jing; Fan Xiujun; Cao Yujing; Duan Enkui . E-mail: duane@ioz.ac.cn

    2006-11-24

    Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas.

  8. Lower Placental Leptin Promoter Methylation in Association with Fine Particulate Matter Air Pollution during Pregnancy and Placental Nitrosative Stress at Birth in the ENVIRONAGE Cohort

    PubMed Central

    Saenen, Nelly D.; Vrijens, Karen; Janssen, Bram G.; Roels, Harry A.; Neven, Kristof Y.; Vanden Berghe, Wim; Gyselaers, Wilfried; Vanpoucke, Charlotte; Lefebvre, Wouter; De Boever, Patrick; Nawrot, Tim S.

    2016-01-01

    Background: Particulate matter with a diameter ≤ 2.5 μm (PM2.5) affects human fetal development during pregnancy. Oxidative stress is a putative mechanism by which PM2.5 may exert its effects. Leptin (LEP) is an energy-regulating hormone involved in fetal growth and development. Objectives: We investigated in placental tissue whether DNA methylation of the LEP promoter is associated with PM2.5 and whether the oxidative/nitrosative stress biomarker 3-nitrotyrosine (3-NTp) is involved. Methods: LEP DNA methylation status of 361 placentas from the ENVIRONAGE birth cohort was assessed using bisulfite-PCR-pyrosequencing. Placental 3-NTp (n = 313) was determined with an ELISA assay. Daily PM2.5 exposure levels were estimated for each mother’s residence, accounting for residential mobility during pregnancy, using a spatiotemporal interpolation model. Results: After adjustment for a priori chosen covariates, placental LEP methylation was 1.4% lower (95% CI: –2.7, –0.19%) in association with an interquartile range increment (7.5 μg/m3) in second-trimester PM2.5 exposure and 0.43% lower (95% CI: –0.85, –0.02%) in association with a doubling of placental 3-NTp content. Conclusions: LEP methylation status in the placenta was negatively associated with PM2.5 exposure during the second trimester, and with placental 3-NTp, a marker of oxidative/nitrosative stress. Additional research is needed to confirm our findings and to assess whether oxidative/nitrosative stress might contribute to associations between PM2.5 and placental epigenetic events. Potential consequences for health during the neonatal period and later in life warrant further exploration. Citation: Saenen ND, Vrijens K, Janssen BG, Roels HA, Neven KY, Vanden Berghe W, Gyselaers W, Vanpoucke C, Lefebvre W, De Boever P, Nawrot TS. 2017. Lower placental leptin promoter methylation in association with fine particulate matter air pollution during pregnancy and placental nitrosative stress at birth in the

  9. CENTRALITY OF THE UMBILICAL CORD INSERTION IN A HUMAN PLACENTA INFLUENCES THE PLACENTAL EFFICIENCY

    PubMed Central

    Yampolsky, Michael; Salafia, Carolyn M.; Shlakhter, Oleksandr; Haas, Danielle; Eucker, Barbara; Thorp, John

    2009-01-01

    Goal: We assess the effect on placental efficiency of the non-centrality of the umbilical cord insertion and on chorionic vascular distribution to determine if cord centrality measurably affects placental function as reflected in birth weight. Materials and Methods: 1,225 placentas collected from a prospective cohort had digital photographs of the chorionic plate. Of these, 1023 were term, 44 had velamentous cord insertion and 12 had missing clinical data, leaving N=967 (94.5 %) cases for analysis. Mathematical tools included a dynamical stochastic growth model of placental vasculature, Fourier analysis of radial parameterization of placental perimeters, and relative chorionic vascular density (a measure of “gaps” in the vascular coverage) derived from manual tracings of the fetal chorionic surface images. Bivariate correlations used Pearson's or Spearman's rank correlation as appropriate, with p<0.05 considered significant. Results: The correlation of the standard deviation of the placental radius (a measure of non-roundness of the placenta) with cord displacement was negligible (r=0.01). Empirical simulations of the vascular growth model with cord displacement showed no deviation from a normal round-to-oval placental shape for cord displacement of 10 – 50% of placental radius. The correlation of the metabolic scaling exponent β with cord displacement measured by Fourier analysis is 0.17 (p < 0.001). Analysis of the chorionic vascular density in traced images shows a high correlation of the relative vascular distance with cord displacement: 0.59 in one set of 12 images, and 0.20 in the other set of 28 images. Conclusion: Non-central cord insertion has little measurable correlation with placental shape in observed or simulated placentas. However, placentas with a displaced cord show a markedly reduced transport efficiency, reflected in a larger value of β and hence in a smaller birth weight for a given placental weight. Placentas with a non-central cord

  10. Placental Growth Measures in Relation to Birth Weight in a Latin American Population.

    PubMed

    Grandi, Carlos; Veiga, Angélica; Mazzitelli, Nancy; Cavalli, Ricardo de Carvalho; Cardoso, Viviane

    2016-08-01

    Introduction The placenta, translates how the fetus experiences the maternal environment and is a principal influence on birth weight (BW). Objective To explore the relationship between placental growth measures (PGMs) and BW in a public maternity hospital. Methods Observational retrospective study of 870 singleton live born infants at Hospital Maternidad Sardá, Universidad de Buenos Aires, Argentina, between January 2011 and August 2012 with complete data of PGMs. Details of history, clinical and obstetrical maternal data, labor and delivery and neonatal outcome data, including placental measures derived from the records, were evaluated. The following manual measurements of the placenta according to standard methods were performed: placental weight (PW, g), larger and smaller diameters (cm), eccentricity, width (cm), shape, area (cm(2)), BW/PW ratio (BPR) and PW/BW ratio (PBR), and efficiency. Associations between BW and PGMs were examined using multiple linear regression. Results Birth weight was correlated with placental weight (R(2) = 0.49, p < 0.001), whereas gestational age was moderately correlated with placental weight (R(2) = 0.64, p < 0.001). By gestational age, there was a positive trend for PW and BPR, but an inverse relationship with PBR (p < 0.001). Placental weight alone accounted for 49% of birth weight variability (p < 0,001), whereas all PGMs accounted for 52% (p < 0,001). Combined, PGMs, maternal characteristics (parity, pre-eclampsia, tobacco use), gestational age and gender explained 77.8% of BW variations (p < 0,001). Among preterm births, 59% of BW variances were accounted for by PGMs, compared with 44% at term. All placental measures except BPR were consistently higher in females than in males, which was also not significant. Indices of placental efficiency showed weakly clinical relevance. Conclusions Reliable measures of placental growth estimate 53.6% of BW variances and project this outcome to a

  11. CD4+ T cells are important mediators of oxidative stress that cause hypertension in response to placental ischemia.

    PubMed

    Wallace, Kedra; Cornelius, Denise C; Scott, Jeremy; Heath, Judith; Moseley, Janae; Chatman, Krystal; LaMarca, Babbette

    2014-11-01

    Preeclampsia is associated with oxidative stress, which is suspected to play a role in hypertension, placental ischemia, and fetal demise associated with the disease. Various cellular sources of oxidative stress, such as neutrophils, monocytes, and CD4(+) T cells have been suggested as culprits in the pathophysiology of preeclampsia. The objective of this study was to examine a role of circulating and placental CD4(+) T cells in oxidative stress in response to placental ischemia during pregnancy. CD4(+) T cells and oxidative stress were measured in preeclamptic and normal pregnant women, placental ischemic and normal pregnant rats, and normal pregnant recipient rats of placental ischemic CD4(+) T cells. Women with preeclampsia had significantly increased circulating (P=0.02) and placental CD4(+) T cells (P=0.0001); lymphocyte secretion of myeloperoxidase (P=0.004); and placental reactive oxygen species (P=0.0004) when compared with normal pregnant women. CD4(+) T cells from placental ischemic rats cause many facets of preeclampsia when injected into normal pregnant recipient rats on gestational day 13. On gestational day 19, blood pressure increased in normal pregnant recipients of placental ischemic CD4(+) T cells (P=0.002) compared with that in normal pregnant rats. Similar to preeclamptic patients, CD4(+) T cells from placental ischemic rats secreted significantly more myeloperoxidase (P=0.003) and induced oxidative stress in cultured vascular cells (P=0.003) than normal pregnant rat CD4(+)Tcells. Apocynin, a nicotinamide adenine dinucleotide phosphate inhibitor, attenuated hypertension and all oxidative stress markers in placental ischemic and normal pregnant recipient rats of placental ischemic CD4(+)Tcells (P=0.05). These data demonstrate an important role for CD4(+) T cells in mediating another factor, oxidative stress, to cause hypertension during preeclampsia.

  12. CD4+T cells are important mediators of oxidative stress that cause hypertension in response to placental ischemia

    PubMed Central

    Wallace, Kedra; Cornelius, Denise C.; Scott, Jeremy; Heath, Judith; Moseley, Janae; Chatman, Krystal; LaMarca, Babbette

    2014-01-01

    Preeclampsia is associated with oxidative stress which is suspected to play a role in hypertension, placental ischemia and fetal demise associated with the disease. Various cellular sources of oxidative stress such as neutrophils, monocytes and CD4+T cells have been suggested as culprits in the pathophysiology of preeclampsia. The objective of this study was to examine a role for circulating and placental CD4+T cells in oxidative stress in response to placental ischemia during pregnancy. CD4+T cells and oxidative stress was measured in preeclamptic and normal pregnant women, placental ischemic and normal pregnant rats and normal pregnant recipient rats of placental ischemic CD4+ T cells. Preeclamptic women had significantly increased circulating (p=0.02) and placental CD4+T cells (p=0.0001); lymphocyte secretion of myeloperoxidase (p=0.004); and placental reactive oxygen species (p=0.0004) compared to normal pregnant women. CD4+T cells from placental ischemic rats cause many facets of preeclampsia when injected into normal pregnant recipient rats on gestational day 13. On gestational day 19 blood pressure increased in normal pregnant recipients of placental ischemic CD4+T cells (p=0.002) compared to normal pregnant rats. Similar to preeclamptic patients, CD4+ T cells from placental ischemic rats secreted significantly more myeloperoxidase (p=0.003) and induced oxidative stress in cultured vascular cells (p=0.003) than normal pregnant rat CD4+Tcells. Apocynin, an NADPH inhibitor, attenuated hypertension, and all oxidative stress markers in placental ischemic and normal pregnant recipient rats of placental ischemic CD4+Tcells (p=0.05). These data demonstrate an important role for CD4+T cells in mediating another factor, oxidative stress, to cause hypertension during preeclampsia. PMID:25259742

  13. Extremely Stable Soluble High Molecular Mass Multi-Protein Complex with DNase Activity in Human Placental Tissue

    PubMed Central

    Burkova, Evgeniya E.; Dmitrenok, Pavel S.; Sedykh, Sergey E.; Buneva, Valentina N.; Soboleva, Svetlana E.; Nevinsky, Georgy A.

    2014-01-01

    Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼1000 kDa) from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs) 4–14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa) as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions. PMID:25426722

  14. Placental proopiomelanocortin gene expression, adrenocorticotropin tissue concentrations, and immunostaining increase throughout gestation and are unaffected by prostaglandins, antiprogestins, or labor.

    PubMed

    Cooper, E S; Greer, I A; Brooks, A N

    1996-12-01

    The objective of this study was to demonstrate the ontogeny of POMC gene expression, the distribution of immunoreactive ACTH, and tissue peptide content within the placenta and fetal membranes and to investigate the regulatory effects of PGs and progesterone during the first trimester and of labor at term. Tissues were collected from the following groups: 1) women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE1 analogue, gemeprost administered vaginally 2-4 h before the procedure or with 600 mg mifepristone 48 h before receiving 1 mg gemeprost vaginally); 2) women undergoing second trimester therapeutic abortion (600 mg mifepristone; 1 mg gemeprost); 3) in association with delivery at term by spontaneous labor; 4) induced labor; or 5) elective caesarean section. ACTH was immunolocalized to the placental cytotrophoblasts in the first trimester and to the syncytiotrophoblasts in the second and third trimester. The intensity of the staining increased with advancing gestation. ACTH immunoreactivity also was localized in the epithelial layer of the amnion, the reticular layer of the chorion, and the decidual stroma. ACTH content measured by RIA in placental extracts increased significantly in the third trimester. In situ hybridization demonstrated expression of POMC messenger RNA in syncytiotrophoblasts and cytotrophoblasts from the first trimester and also demonstrated a significant increase in POMC gene expression with advancing gestation. The localization and staining intensity for ACTH and POMC gene expression were not affected by the administration of PGs or mifepristone or by labor at term. These data demonstrate the localization of ACTH immunoreactivity within the placenta throughout pregnancy, supporting the hypothesis that the placenta may activate and maintain the maternal and/or fetal hypothalamo-pituitary-adrenal axis throughout pregnancy.

  15. Fetal-maternal nitrite exchange in sheep: experimental data, a computational model and an estimate of placental nitrite permeability

    PubMed Central

    Schroeder, Hobe J.; Kanda, Eriko; Power, Gordon G.; Blood, Arlin B.

    2016-01-01

    Introduction Nitrite conveys NO-bioactivity that may contribute to the high-flow, low-resistance character of the fetal circulation. Fetal blood nitrite concentrations depend partly on placental permeability which has not been determined experimentally. We aimed to extract the placental permeability-surface (PS) product for nitrite in sheep from a computational model. Methods An eight-compartment computational model of the fetal-maternal unit was constructed (Matlab® (R2013b (8.2.0.701), MathWorks Inc., Natick, MA). Taking into account fetal and maternal body weights, four variables (PS, the rate of nitrite metabolism within red cells, and two nitrite distribution volumes, one with and one without nitrite metabolism), were varied to obtain optimal fits to the experimental plasma nitrite profiles observed following the infusion of nitrite into either the fetus (n=7) or the ewe (n=8). Results The model was able to replicate the average and individual nitrite-time profiles (r2 > 0.93) following both fetal and maternal nitrite infusions with reasonable variation of the four fitting parameters. Simulated transplacental nitrite fluxes were able to predict umbilical arterial-venous nitrite concentration differences that agreed with experimental values. The predicted PS values for a 3 kg sheep fetus were 0.024±0.005 l·min−1 in the fetal-maternal direction and 0.025±0.003 l·min−1 in the maternal-fetal direction (mean±SEM). These values are many-fold higher than the reported PS product for chloride anions across the sheep placenta. Conclusion The result suggests a transfer of nitrite across the sheep placenta that is not exclusively by simple diffusion through water-filled channels. PMID:26907384

  16. The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

    PubMed

    Cooley, Sharon M; Donnelly, Jennifer C; Walsh, Thomas; McMahon, Corrina; Gillan, John; Geary, Michael P

    2011-03-01

    To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. Placental site and architecture impact on the incidence of maternal and fetal disease.

  17. Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker

    PubMed Central

    Stinghen, Sérvio T.; Moura, Juliana F.; Zancanella, Patrícia; Rodrigues, Giovanna A.; Pianovski, Mara A.; Lalli, Enzo; Arnold, Dodie L.; Minozzo, João C.; Callefe, Luis G.; Ribeiro, Raul C.; Figueiredo, Bonald C.

    2006-01-01

    Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes. PMID:17489017

  18. Role of transporters in placental transfer of drugs

    SciTech Connect

    Ganapathy, Vadivel . E-mail: vganapat@mail.mcg.edu; Prasad, Puttur D.

    2005-09-01

    Human placenta functions as an important transport organ that mediates the exchange of nutrients and metabolites between maternal and fetal circulations. This function is made possible because of the expression of a multitude of transport proteins in the placental syncytiotrophoblast with differential localization in the maternal-facing brush border membrane versus the fetal-facing basal membrane. Even though the physiological role of most of these transport proteins is to handle nutrients, many of them interact with xenobiotics and pharmacological agents. These transport proteins therefore play a critical role in the disposition of drugs across the maternal-fetal interface, with some transporters facilitating the entry of drugs from maternal circulation into fetal circulation whereas others preventing such entry by actively eliminating drugs from the placenta back into maternal circulation. The net result as to whether the placenta enhances the exposure of the developing fetus to drugs and xenobiotics or functions as a barrier to protect the fetus from such agents depends on the types of transporters expressed in the brush border membrane and basal membrane of the syncytiotrophoblast and on the functional mode of these transporters (influx versus efflux)

  19. Placental autophagy regulation by the BOK-MCL1 rheostat.

    PubMed

    Kalkat, Manpreet; Garcia, Julia; Ebrahimi, Jessica; Melland-Smith, Megan; Todros, Tullia; Post, Martin; Caniggia, Isabella

    2013-12-01

    Autophagy is the catabolic degradation of cellular cytoplasmic constituents via the lysosomal pathway that physiologically elicits a primarily cytoprotective function, but can rapidly be upregulated in response to stressors thereby inducing cell death. We have reported that the balance between the BCL2 family proteins BOK and MCL1 regulates human trophoblast cell fate and its alteration toward cell death typifies preeclampsia. Here we demonstrate that BOK is a potent inducer of autophagy as shown by increased LC3B-II production, autophagosomal formation and lysosomal activation in HEK 293. In contrast, using JEG3 cells we showed that prosurvival MCL1 acts as a repressor of autophagy via an interaction with BECN1, which is abrogated by BOK. We found that MCL1-cleaved products, specifically MCL1c157, trigger autophagy while the splicing variant MCL1S has no effect. Treatment of JEG3 cells with nitric oxide donor SNP resulted in BOK-MCL1 rheostat dysregulation, favoring BOK accumulation, thereby inducing autophagy. Overexpression of MCL1 rescued oxidative stress-induced autophagy. Of clinical relevance, we report aberrant autophagy levels in the preeclamptic placenta due to impaired recruitment of BECN1 to MCL1. Our data provided the first evidence for a key role of the BOK-MCL1 system in regulating autophagy in the human placenta, whereby an adverse environment as seen in preeclampsia tilts the BOK-MCL1 balance toward the build-up of isoforms that triggers placental autophagy.

  20. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    NASA Technical Reports Server (NTRS)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  1. Pseudo-placentational endometrial cysts in a bitch.

    PubMed

    Bartel, C; Schönkypl, S; Walter, I

    2010-02-01

    Cystic alterations of the canine endometrium compromise reproduction and fertility of the bitch and may lead to life-threatening diseases, such as pyometra. Even without clinical evidence, reduction of the uterine lumen by cysts implicates disturbances during migration, nidation and development of the embryo. Several studies point to the high variability of morphology of uterine endometrial cysts but they lack detailed analyses of alterations. In the present study, immunohistochemistry was used to investigate the expression of steroid hormone receptors (oestrogen, progesterone), proliferation activity, inflammation and infection in the cystic affected tissue regions in contrast to the normal endometrium. Oestrogen receptor expression showed a high density of receptors throughout the surface epithelial cells, crypt epithelial cells, glandular epithelial cells and stromal cells of the normal endometrium as well as the cystic affected regions. Proliferation in the cysts was verified in the middle and basal cells of the crypts. Neither in the endometrium nor in the cysts inflammatory processes or evidence of infection could be detected. Furthermore, lectin histochemistry and electron microscopic methods showed that lectin binding patterns and cell morphology of internal epithelial lining and surface epithelium of the cysts can be used to characterize and distinguish different types of cystic alterations. Analogies between epithelial cells of the glandular chambers of the canine placenta and the cystic cellular morphology, steroid hormone receptor distribution as well as lectin binding patterns of the endometrial cysts, as observed in this study, suggest to introduce the term 'pseudo-placentational endometrial cysts'.

  2. Solubilized placental membrane protein inhibits insulin receptor tyrosine kinase activity

    SciTech Connect

    Strout, H.V. Jr.; Slater, E.E.

    1987-05-01

    Regulation of insulin receptor (IR) tyrosine kinase (TK) activity may be important in modulating insulin action. Utilizing an assay which measures IR phosphorylation of angiotensin II (AII), the authors investigated whether fractions of TX-100 solubilized human placental membranes inhibited IR dependent AII phosphorylation. Autophosphorylated IR was incubated with membrane fractions before the addition of AII, and kinase inhibition measured by the loss of TSP incorporated in AII. An inhibitory activity was detected which was dose, time, and temperature dependent. The inhibitor was purified 200-fold by sequential chromatography on wheat germ agglutinin, DEAE, and hydroxyapatite. This inhibitory activity was found to correlate with an 80 KD protein which was electroeluted from preparative slab gels and rabbit antiserum raised. Incubation of membrane fractions with antiserum before the IRTK assay immunoprecipitated the inhibitor. Protein immunoblots of crude or purified fractions revealed only the 80 KD protein. Since IR autophosphorylation is crucial to IRTK activity, the authors investigated the state of IR autophosphorylation after treatment with inhibitor; no change was detected by phosphoamino acid analysis.

  3. Conservative management of placenta previa complicated by abnormal placentation.

    PubMed

    Bręborowicz, Grzegorz H; Markwitz, Wiesław; Gaca, Michał; Koziołek, Agnieszka; Ropacka-Lesiak, Mariola; Dera, Anna; Brych, Mariusz; Szymankiewicz-Bręborowicz, Marta; Kruszyński, Grzegorz; Gruca-Stryjak, Karolina; Madejczyk, Mateusz; Szpera-Goździewicz, Agata; Krzyścin, Mariola

    2013-07-01

    Abnormal implantation of placenta previa is life-threatening condition. The purpose of this study was to evaluate the impact of the conservative management of pregnancies with such complication on maternal morbidity rate and the chance for uterine preservation (fertility). Eleven patients with abnormal implantation of placenta previa were analyzed prospectively. This complication was diagnosed antenatally by two-dimensional ultrasound and color flow Doppler. The following outcomes were analyzed: need for blood transfusion, admission and duration of stay in intensive care unit, infections, coagulopathies, time between cesarean section and delivery of placenta, hysterectomy and preservation of uterus. Among the 20 085 women who had a singleton gestation, 11 (0.054%) were identified with placenta previa with abnormal placentation. In five patients (group A), hysterectomy was performed because of hemorrhage or placenta ablation. In six patients (group B), conservative management succeeded and placenta were preserved. In group A, placenta were delivered earlier (2 d-8 weeks) in comparison with group B (6-15 weeks). Estimated blood loss during the delayed delivery of placenta was higher in the group with hysterectomy (respectively, 450-1600 and 300-500 ml). Conservative management of placenta previa with abnormal implantation decreases the risk of severe hemorrhage at the time of delivery and can preserve fertility.

  4. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    NASA Technical Reports Server (NTRS)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  5. [Placental epigenetic programming in intrauterine growth restriction (IUGR)].

    PubMed

    Casanello, Paola; Castro-Rodríguez, José A; Uauy, Ricardo; Krause, Bernardo J

    2016-01-01

    Intrauterine growth restriction (IUGR) is a perinatal condition affecting foetal growth, with under the 10th percentile of the weight curve expected for gestational age. This condition has been associated with higher cardiovascular and metabolic risk and post-natal obesity. There are also major changes in placental function, and particularly in a key molecule in this regulation, nitric oxide. The synthesis of nitric oxide has numerous control mechanisms and competition with arginase for their common substrate, the amino acid L-arginine. This competition is reflected in various vascular diseases and particularly in the endothelium of the umbilical vessels of babies with IUGR. Along with this, there is regulation at the epigenetic level, where methylation in specific regions of some gene promoters, such as the nitric oxide synthase, regulating their expression. It is currently of great interest to understand the mechanisms by which diseases such as IUGR may be conditioned, particularly by maternal nutritional and metabolic conditions, and epigenetic mechanisms that could eventually be modifiable, and thus a focus of interest for health interventions. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. The effect of placental subfractions on Trypanosoma cruzi.

    PubMed

    Frank, F; Sartori, M J; Asteggiano, C; Lin, S; de Fabro, S P; Fretes, R E

    2000-10-01

    Five subfractions were collected from six term placentas by mincing and differential centrifugation: homogenate, nuclear, mitochondrial, lysosomal, and supernatant. The effect of each subfraction on Trypanosoma cruzi was assessed by trypan blue exclusion, relative infectivity of mice, and penetration of susceptible cultured VERO cells. Ultrastructural changes in trypomastigotes were identified after high cell mortality was shown by dye exclusion following treatment with lysosomal and supernatant fractions. Trypomastigotes treated with other subfractions or preheated subfractions, those recovered from infected VERO cells, and controls remained unaffected. This was confirmed by the ability of treated trypomastigotes to infect mice or to penetrate susceptible cultured VERO cells. There were a 48% decrease in parasitemia and fewer myocardial lesions in Balb/c mice following treatment with the lysosomal subfraction compared to homogenate and controls. VERO cells were invaded about half as often after lysosomal treatment compared to controls (P < 0. 05); an 11% decrease in cell invasion following homogenate treatment was not significant. Placental lysosomal enzyme activity was unaffected by trypomastigotes. Human placentas contain one or more heat-labile substances in lysosomal and supernatant subfractions which inhibit or injure trypomastigotes of T. cruzi in cell-free systems. Copyright 2000 Academic Press.

  7. Epidermal growth factor stimulates mouse placental lactogen I but inhibits mouse placental lactogen II secretion in vitro.

    PubMed Central

    Yamaguchi, M; Ogren, L; Endo, H; Thordarson, G; Kensinger, R; Talamantes, F

    1992-01-01

    This study was undertaken to determine whether epidermal growth factor (EGF) regulates the secretion of mouse placental lactogen (mPL)-I and mPL-II. Primary cell cultures were prepared from placentas from days 7, 9, and 11 of pregnancy and cultured for up to 5 days. Addition of EGF (20 ng/ml) to the medium resulted in significant stimulation of mPL-I secretion by the second day of culture in cells from days 7 and 9 of pregnancy and significant inhibition of mPL-II secretion by the third or fourth day of culture in cells from days 7, 9, and 11. Dose-response studies carried out with cells from day 7 of pregnancy demonstrated that the minimum concentration of EGF that stimulated mPL-I secretion and inhibited mPL-II secretion was 1.0 ng/ml. EGF did not affect the DNA content of the cells or cell viability, assessed by trypan blue exclusion, nor did it have a general effect on protein synthesis. There are three types of PL-containing giant cells in mouse placental cell cultures: cells that contain either mPL-I or mPL-II and cells that contain both hormones. Immunocytochemical analysis and the reverse hemolytic plaque assay indicated that EGF treatment was accompanied by a significant increase in the number of cells that produce mPL-I, but among the PL cells that contained mPL-I, there was no change in the fraction of cells that contained only mPL-I or the fraction that contained both mPL-I and mPL-II. In contrast, EGF treatment did affect the distribution of mPL-II among PL cells. In control cultures, about 75% of the cells that contained mPL-II also contained mPL-I, but in EGF-treated cultures, all of the cells that contained mPL-II also contained mPL-I. These data suggest that EGF regulates mPL-I and mPL-II secretion at least partly by regulating PL cell differentiation. PMID:1454826

  8. RNA-seq analysis of the rat placentation site reveals maternal obesity-associated changes in placental and offspring thyroid hormone signaling

    USDA-ARS?s Scientific Manuscript database

    Introduction In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unkno...

  9. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

    PubMed

    Bleker, O P; Buimer, M; van der Post, J A M; van der Veen, F

    2006-01-01

    In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

  10. Placental infection by two subpopulations of Trypanosoma cruzi is conditioned by differential survival of the parasite in a deleterious placental medium and not by tissue reproduction.

    PubMed

    Triquell, María F; Díaz-Luján, Cintia; Freilij, Hector; Paglini, Patricia; Fretes, Ricardo E

    2009-10-01

    Chagas disease is caused by Trypanosoma cruzi, which can be transmitted to the fetus via the transplacental route. Factors that may be involved in transplacental transmission include parasite strain and placental immunological competence. The aim of this work was to compare the biological differences between two subpopulations of T. cruzi with respect to their interaction with the human placenta in vitro. We found that the Tulahuen strain (sublineage TcIIe) and another strain isolated from a congenitally infected newborn child had similar rates of productive infection in human chorionic villi in vitro, with similar deleterious nitric oxide levels between the two strains. We also found that the congenital T. cruzi stock had a greater ability than the Tulahuen strain to survive in the placental deleterious media, with the difference acquiring more importance considering the low reproductive rate of both subpopulations of T. cruzi within placental cells. As the presence of T. cruzi is a necessary condition to produce congenital transmission, we propose that the different survival rates of strains of T. cruzi in an adverse placental environment offer an opportunity for the parasite to infect the placenta in order to produce a sustainable infection during pregnancy, with the subsequent possibility of infecting the fetus.

  11. The Placental Microbiota Is Altered among Subjects with Gestational Diabetes Mellitus: A Pilot Study.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Mao, Lili; Yu, Miao; Xu, Jianping; Wang, Tong

    2017-01-01

    Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother and child. However, the associations between human placental microbiota and GDM are poorly understood. We aimed to profile the placental microbiota of GDM and further define whether or not certain placental microbiota taxon correlates with specific clinical characteristics. Placenta were collected from GDM women and women with normal pregnancies (n = 10, in each group) consecutively recruited at Peking Union Medical College Hospital. The anthropometric parameters of mother and infant, and cord blood hormones, including insulin, leptin and insulin-like growth factor-1 (IGF-1) were measured. Bacterial genomic DNA was isolated using magnetic beads and the human placental microbiota was analyzed using the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. It showed there was no statistical difference in the clinical characteristics of mothers and infants, such as BMI at the beginning of pregnancy and gestational weight gain (GWG), birth weight, and cord blood hormones, including insulin, leptin and IGF-1. We found that the placental microbiota is composed of four dominant phyla from Proteobacteria (the most abundant), Bacteroidetes, Actinobacteria and Firmicutes, with the proportion of Proteobacteria increased, and Bacteroidetes and Firmicutes were decreased of women with GDM. Further analyses suggested that bacterial taxonomic composition of placentas from the phylum level down to the bacteria level, differed significantly between women with GDM and non-GDM women with normal pregnancies. Regression analysis showed a cluster of key operational taxonomic units (OTUs), phyla and genera were significantly correlated with GWG during pregnancy of mothers, and cord blood insulin, IGF-1 and leptin concentrations. In conclusion, our novel study showed that a distinct placental microbiota profile is present in GDM, and is associated

  12. Placental development during early pregnancy in sheep: Effects of embryo origin on vascularization

    PubMed Central

    Grazul-Bilska, Anna T.; Johnson, Mary Lynn; Borowicz, Pawel P.; Bilski, Jerzy J.; Cymbaluk, Taylor; Norberg, Spencer; Redmer, Dale A.; Reynolds, Lawrence P.

    2014-01-01

    Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from natural mating (NAT-ET), or in vitro fertilization (IVF) or activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than othe