placentation. For example, total score of 223/260 had a probability of 0.7 for massive transfusion. Hosmer-Lemeshow goodness-of-fit test indicated that the model was suitable (p>0.05). The area under the receiver operating characteristics curve (AUC) was 0.922 [95% confidence interval (CI) 0.89–0.95]. In external validation, the discrimination was good, with an AUC value of 0.833 (95% CI 0.70–0.92) for this model. Nomogram calibration plots indicated good agreement between the predicted and observed outcomes, exhibiting close approximation between the predicted and observed probability.CONCLUSION: We constructed a scoring model for predicting massive transfusion during cesarean section in women with placenta previa. This model may help in determining the need to prepare an appropriate amount of blood products and the optimal timing of blood transfusion.]]>
Area Under Curve ; Blood Transfusion ; Calibration ; Cesarean Section ; Cohort Studies ; Discrimination (Psychology) ; Early Intervention (Education) ; Erythrocytes ; Female ; Humans ; Logistic Models ; Maternal Age ; Nomograms ; Placenta Previa ; Placenta ; Placentation ; Postpartum Hemorrhage ; Pregnancy ; ROC Curve ; Ultrasonography

OBJECTIVE: To evaluate the safety and efficacy of prophylactic uterine artery embolization (UAE) before obstetrical procedures with high risk for massive bleeding. MATERIALS AND METHODS: A retrospective review of 29 female patients who underwent prophylactic UAE from June 2009 to February 2014 was performed. Indications for prophylactic UAE were as follows: dilatation and curettage (D&C) associated with ectopic pregnancy (cesarean scar pregnancy, n = 9; cervical pregnancy, n = 6), termination of pregnancy with abnormal placentation (placenta previa, n = 8), D&C for retained placenta with vascularity (n = 5), and D&C for suspected gestational trophoblastic disease (n = 1). Their medical records were reviewed to evaluate the safety and efficacy of UAE. RESULTS: All women received successful bilateral prophylactic UAE followed by D&C with preservation of the uterus. In all patients, UAE followed by obstetrical procedure prevented significant vaginal bleeding on gynecologic examination. There was no major complication related to UAE. Vaginal spotting continued for 3 months in three cases. Although oligomenorrhea continued for six months in one patient, normal menstruation resumed in all patients afterwards. During follow-up, four had subsequent successful natural pregnancies. Spontaneous abortion occurred in one of them during the first trimester. CONCLUSION: Prophylactic UAE before an obstetrical procedure in patients with high risk of bleeding or symptomatic bleeding may be a safe and effective way to manage or prevent serious bleeding, especially for women who wish to preserve their fertility.
Abortion, Spontaneous ; Cicatrix ; Dilatation and Curettage ; Female ; Fertility ; Follow-Up Studies ; Gestational Trophoblastic Disease ; Hemorrhage* ; Humans ; Medical Records ; Menstruation ; Metrorrhagia ; Oligomenorrhea ; Placenta, Retained ; Placentation ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy, Ectopic ; Retrospective Studies ; Uterine Artery Embolization* ; Uterine Artery* ; Uterine Hemorrhage ; Uterus

OBJECTIVETo investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) exposure on the growth and development of placenta, uterine natural killer (uNK) cell number and angiogenesis at the maternal-fetal interface in pregnant mice.

METHODSFrom day 1 of pregnancy, pregnant mice were exposed daily to DEHP by oral gavage at 125, 250, or 500 mg/kg for 13 consecutive days. The uterine and placental tissues were then harvested for HE staining and immunohistochemistry to examine the effect of DEHP exposure on the growth and development of the placenta and angiogenesis and uNK cell number at the maternal-fetal interface.

RESULTSCompared with the control group, the mice exposed to 500 mg/kg DEHP, but not those exposed to 125 and 250 mg/kg, showed significantly reduced number of embryo implantation (P<0.05). DEHP exposure significantly increased the rate of abortion. DEHP exposure at 125, 250, and 500 mg/kg significantly and dose-dependently lowered the placental weight compared with that in the control group (0.0637±0.0133, 0.0587±0.0176, 0.0524±0.0183 g vs 0.0786±0.0143 g, respectively; P<0.01), and significantly reduced the total area of the placenta and area of spongiotrophoblasts. DEHP exposure resulted in a significant reduction in the number of fetal vascular branches, and collapse and atresia of blood vessels. The mice exposed to DEHP at 125, 250, and 500 mg/kg had significantly lowered numbers of uNK cells (83.2±10.3, 60.7±12.4, and 50.4±14.5/HP, respectively) as compared with the control group (105.1±14.2/HP) at the maternal-fetal interface (P<0.01).

CONCLUSIONDEHP exposure significantly affects the growth and development of the placenta in mice possibly by suppressing angiogenesis and reducing uNK cell number at the maternal-fetal interface during pregnancy.

Animals ; Diethylhexyl Phthalate ; adverse effects ; Embryo Implantation ; Female ; Fetal Blood ; Killer Cells, Natural ; cytology ; Maternal Exposure ; adverse effects ; Mice ; Neovascularization, Physiologic ; Placenta ; drug effects ; Placentation ; drug effects ; Pregnancy ; Uterus ; drug effects

Preeclampsia is one of the most common complications of pregnancy that is prevalent worldwide, resulting in substantial maternal and neonatal morbidity and mortality. Although the cause remains unclear, preeclampsia may be initiated by abnormal placentation and reduced placental perfusion, followed by an imbalance of angiogenic and antiangiogenic factors and subsequent systemic endothelial dysfunction. High level of antiangiogenic factors, such as soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR-1, also known as sFlt-1) and soluble endoglin, and low levels of angiogenic factors, such as free maternal VEGF and placental growth factor (PlGF), are associated with preeclampsia. Angiogenic and antiangiogenic factors also play an important role during lung angiogenesis, and an imbalance between the two types of factors triggered by inflammation disrupts angiogenesis in bronchopulmonary dysplasia (BPD). Because preeclampsia represents an antiangiogenic state, preterm infants born to mothers with preeclampsia would be at increased risk of developing BPD due to impaired lung development. Recently, preeclampsia has been shown to be independently associated with a high risk for BPD. I have reviewed recent progress in research concerning the correlation between preeclampsia and BPD in aspect of pathophysiology and epidemiology.
Angiogenesis Inducing Agents ; Bronchopulmonary Dysplasia* ; Epidemiology ; Humans ; Infant, Newborn ; Infant, Premature ; Inflammation ; Lung ; Mortality ; Mothers ; Perfusion ; Placentation ; Pre-Eclampsia* ; Pregnancy ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1

Stress coping mechanisms are critical to minimize or overcome damage caused by ever changing environmental conditions. They are designed to promote cell survival. The unfolded protein response (UPR) pathway is mobilized in response to the accumulation of unfolded proteins, ultimately in order to regain endoplasmic reticulum (ER) homeostasis. Various elements of coping responses to ER stress including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been identified and were found to be inducible in oocytes and preimplantation embryos, suggesting that, as a normal part of the cellular adaptive mechanism, these coping responses, including the UPR, play a pivotal role in the development of preimplantation embryos. As such, the UPR-associated molecules and pathways may become useful markers for the potential diagnosis of stress conditions for preimplantation embryos. After implantation, ER stress-induced coping responses become physiologically important for a normal decidual response, placentation, and early organogenesis. Attenuation of ER stress coping responses by tauroursodeoxycholate and salubrinal was effective for prevention of cell death of cultured embryos. Further elucidation of new and relevant ER stress coping responses in periimplantation embryos might contribute to a comprehensive understanding of the regulation of normal development of embryonic development and potentiation of embryonic development in vitro.
Blastocyst ; Cell Death ; Cell Survival ; Diagnosis ; Embryonic Development ; Embryonic Structures* ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress* ; Female ; Homeostasis ; Oocytes ; Organogenesis ; Placentation ; Pregnancy ; Unfolded Protein Response

Galectins are an evolutionarily ancient and widely expressed family of lectins that have unique glycan-binding characteristics. They are pleiotropic regulators of key biological processes, such as cell growth, proliferation, differentiation, apoptosis, signal transduction, and pre-mRNA splicing, as well as homo- and heterotypic cell-cell and cell-extracellular matrix interactions. Galectins are also pivotal in immune responses since they regulate host-pathogen interactions, innate and adaptive immune responses, acute and chronic inflammation, and immune tolerance. Some galectins are also central to the regulation of angiogenesis, cell migration and invasion. Expression and functional data provide convincing evidence that, due to these functions, galectins play key roles in shared and unique pathways of normal embryonic and placental development as well as oncodevelopmental processes in tumorigenesis. Therefore, galectins may sometimes act as double-edged swords since they have beneficial but also harmful effects for the organism. Recent advances facilitate the use of galectins as biomarkers in obstetrical syndromes and in various malignancies, and their therapeutic applications are also under investigation. This review provides a general overview of galectins and a focused review of this lectin subfamily in the context of inflammation, infection and tumors of the female reproductive tract as well as in normal pregnancies and those complicated by the great obstetrical syndromes.
Apoptosis ; Biomarkers ; Biological Processes ; Carcinogenesis ; Cell Movement ; Epigenomics ; Female ; Galectins* ; Host-Pathogen Interactions ; Humans ; Immune Tolerance ; Inflammation* ; Lectins ; Placentation ; Pregnancy ; Pregnancy Complications* ; RNA Precursors ; Signal Transduction

The milk fat globule-EGF-factor 8 protein (MFG-E8) has been identified in various tissues, where it has an important role in intercellular interactions, cellular migration, and neovascularization. Previous studies showed that MFG-E8 is expressed in different cell types under normal and pathophysiological conditions, but its expression in hematopoietic stem cells (HSCs) during hematopoiesis has not been reported. In the present study, we investigated MFG-E8 expression in multiple hematopoietic tissues at different stages of mouse embryogenesis. Using immunohistochemistry, we showed that MFG-E8 was specifically expressed in CD34+ HSCs at all hematopoietic sites, including the yolk sac, aorta-gonad-mesonephros region, placenta and fetal liver, during embryogenesis. Fluorescence-activated cell sorting and polymerase chain reaction analyses demonstrated that CD34+ cells, purified from the fetal liver, expressed additional HSC markers, c-Kit and Sca-1, and that these CD34+ cells, but not CD34- cells, highly expressed MFG-E8. We also found that MFG-E8 was not expressed in HSCs in adult mouse bone marrow, and that its expression was confined to F4/80+ macrophages. Together, this study demonstrates, for the first time, that MFG-8 is expressed in fetal HSC populations, and that MFG-E8 may have a role in embryonic hematopoiesis.
Animals ; Antigens, CD34/analysis ; Antigens, Surface/*analysis ; Bone Marrow/ultrastructure ; Female ; Hematopoietic Stem Cells/*cytology ; Liver/embryology ; Mice/*embryology ; Milk Proteins/*analysis ; Placentation ; Pregnancy

Acute atherosis is unique vascular changes of the placenta associated with poor placentation. It is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis of the arterial wall, perivascular lymphocytic infiltration, and it is histologically similar to early-stage atherosclerosis. Acute atherosis is rare in normal pregnancies, but is frequently observed in non- transformed spiral arteries in abnormal pregnancies, such as preeclampsia, small for gestational age (SGA), fetal death, spontaneous preterm labor and preterm premature rupture of membranes. In preeclampsia, spiral arteries fail to develop physiologic transformation and retain thick walls and a narrow lumen. Failure of physiologic transformation of spiral arteries is believed to be the main cause of uteroplacental ischemia, which can lead to the production of anti-angiogenic factors and induce endothelial dysfunction and eventually predispose the pregnancy to preeclampsia. Acute atherosis is more frequently observed in the spiral arteries of the decidua of the placenta (parietalis or basalis) than in the decidual or myometrial segments of the placental bed. The presence and deeper location of acute atherosis is associated with poorer pregnancy outcomes, more severe disease, earlier onset of preeclampsia, and a greater frequency of SGA neonates in patients with preeclampsia. Moreover, the idea that the presence of acute atherosis in the placenta may increase the risk of future cardiovascular disease in women with a history of preeclampsia is of growing concern. Therefore, placental examination is crucial for retrospective investigation of pregnancy complications and outcomes, and accurate placental pathology based on universal diagnostic criteria in patients with abnormal pregnancies is essential for clinicopathologic correlation.
Arteries* ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Decidua ; Female ; Fetal Death ; Foam Cells ; Gestational Age ; Humans ; Infant, Newborn ; Ischemia ; Membranes ; Necrosis ; Obstetric Labor, Premature ; Pathology ; Placenta ; Placentation ; Pre-Eclampsia ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Retrospective Studies ; Rupture

OBJECTIVE: The aim of this study was to evaluate indications, efficacy, and complications associated with pelvic arterial embolization (PAE) for postpartum hemorrhage (PPH). METHODS: We retrospectively reviewed the medical records of 117 consecutive patients who underwent PAE for PPH between January 2006 and June 2013. RESULTS: In our single-center study, 117 women underwent PAE to control PPH refractory to conservative management including uterine massage, use of uterotonic agents, surgical repair of genital tract lacerations, and removal of retained placental tissues. Among 117 patients, 69 had a vaginal delivery and 48 had a Cesarean section. The major indication for embolization was uterine atony (54.7%). Other causes were low genital tract lacerations (21.4%) and abnormal placentation (14.5%). The procedure showed a clinical success rate of 88.0% with 14 cases of PAE failure; there were 4 hemostatic hysterectomies and 10 re-embolizations. On univariate analysis, PAE failure was associated with overt disseminated intravascular coagulation (P=0.009), transfusion of more than 10 red blood cell units (RBCUs, P=0.002) and embolization of both uterine and ovarian arteries (P=0.003). Multivariate analysis showed that PAE failure was only associated with transfusions of more than 10 RBCUs (odds ratio, 8.011; 95% confidence interval, 1.531-41.912; P=0.014) and embolization of both uterine and ovarian arteries (odds ratio, 20.472; 95% confidence interval, 2.715-154.365; P=0.003), which were not predictive factors, but rather, were the results of longer time for PAE. Three patients showed uterine necrosis and underwent hysterectomy. CONCLUSION: PAE showed high success rates, mostly without procedure-related complications. Thus, it is a safe and effective adjunct or alternative to hemostatic hysterectomy, when primary management fails to control PPH.
Arteries ; Cesarean Section ; Disseminated Intravascular Coagulation ; Erythrocytes ; Female ; Humans ; Hysterectomy ; Lacerations ; Massage ; Medical Records ; Multivariate Analysis ; Necrosis ; Placentation ; Postpartum Hemorrhage* ; Postpartum Period* ; Pregnancy ; Retrospective Studies* ; Uterine Inertia

OBJECTIVE: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. METHODS: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. RESULTS: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. CONCLUSION: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.
Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Matrix Metalloproteinase 9 ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Placenta ; Placentation ; Plasma ; Pre-Eclampsia ; Pregnant Women ; RNA ; RNA, Messenger ; RNA, Small Interfering ; Transfection ; Trophoblasts ; Up-Regulation