Placenta In Order Research Articles

Peripartum Hysterectomy Outcomes: Our Eleven-Year Experience at a Tertiary Care Hospital.

To investigate the outcomes of peripartum hysterectomies (PHs) conducted to prevent maternal morbidity and mortality at a tertiary care hospital with 15,000 deliveries per year. Patients who underwent PHs during delivery and/or within 24h of delivery between the years 2011-2022 were retrospectively evaluated. Hysterectomies not performed in the peripartum period, cases that were managed by methods such as balloon tamponade, compression suture, or arterial ligation rather than hysterectomy, and hysterectomies performed before 20weeks were excluded. Obstetric and demographic characteristics of the cases, as well as indications and outcomes of PH, were investigated. Among the 130 patients who underwent PH, 4 (3.04%) patients delivered vaginally, 1 (0.7%) patient delivered vaginally after cesarean section, 12 (9.2%) patients delivered by primary cesarean section, and 113 (86.9%) patients delivered by secondary cesarean section. Placenta accreta spectrum disorder was the reason for PH in 54.6% (n = 71) of the cases while 16.1% (n = 21) underwent PH due to uterine atony. The PH rate was 0.75 per 1000 births, and the maternal mortality rate was 7.6 per 1000 hysterectomies in this study. Obstetricians in developed/ing countries support the active management of the third stage of labor mainly to mitigate the preventable risk factors of post-/peri-partum hemorrhage. The current study suggests that obstetricians need to focus on the placenta in order to reduce PH.

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine-protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

Molecular Docking and Analysis of some Ligands on Var2csA Target

Purpose: Prevalence of malaria during pregnancy and the spate of drug resistance by malaria parasites have constantly impacted maternal, perinatal and neonatal outcomes, especially in sub-Saharan Africa. This study aims to discover “in silico” non-recombinant molecules which can interact with placental chondroitin sulfate to inhibit binding or displace bound var2csA from the placenta in order to prevent pregnancy associated malaria.
 Methodology: Protein data bank (rcsb.org) and PubChem were used to download the chemical structures of the receptor (3bqk) and those of the ligands. Canonical SMILES and other information about the ligands and the receptor were extracted from PubChem. Toxtree, Toxicity Estimation Software Tool (TEST), SwissADMET, Molinspiration and Lazar Toxicity Predicter were employed to test various toxicity and safety parameters of lead compounds. The structure of the macromolecule – chondroitin sulfate A (CSA) was retrieved by searching in the protein data bank (PDB) (rcsb.org/structure/3bqk); downloaded, and saved as a PDB format.
 Findings: Molecular modeling and toxicity predictors used in this study indicated that among the ligands screened, IH3 had the lowest binding energy of -9.8Kcal/mol while var2csA had -2.8Kcal/mol. Var2csA is parasite’s adhesive protein. It was also observed that out of the 90 ligands (binding affinity range -9.8 to -1.0 Kcal/mol) screened, IH3 (-9.8Kcal/mol), FAD (-8.4 Kcal/mol), NDP (-8.2 Kcal/mol), A5A (-8.2 Kcal/mol), ABO (-8.1 Kcal/mol), IH2 (-7.8 Kcal/mol), 2RT (-7.7 Kcal/mol), CRO (-7.7 Kcal/mol) and IH1 (-7.7 Kcal/mol) appear to be the most promising lead compounds to occupy var2csA binding pocket in pCSA in order to prevent adhesion of malaria infected erythrocytes to the placenta. SwissADME and Molinspiration Cheminformatics for LogP (mean of 1.07 and range of -2.79 to 4.18) of the lead compounds showed no correlations between lipophilicity and interaction with receptors. Of all the compounds selected for analysis, only ABO and 2RT exhibited drug-like properties based on Ghose, Lipinski and Veber filters.
 Conclusion: Data obtained from the study therefore suggests that IH3, FAD, NDP, A5A, ABO, IH2, 2RT, CRO, IH1 and var2csA make favourable lead candidates for targeting pCSA and therefore require further in vitro and in vivo evaluations.
 Recommendation: This study therefore recommends the repurposing and extending the use of flavin adenine dinucleotide (FAD) to cover prophylactic management of malaria among pregnant women.

Dynamic Immune Status of Pregnancy and Dermatological Diseases

Dynamic changes of immune system in the various stages of pregnancy affect the course of various diseases afflicting the mother alongside determining how pregnancy affects these diseases. To understand this, a thorough knowledge on how the immune system differs in pregnancy is essential. The complex interplay between the maternal and fetal immune systems via placenta in order to maintain the pregnancy leads to waxing and waning of immune responses in both mother and fetus. This dynamic nature of immune responses can heavily influence the manifestations and severity of several dermatological diseases, whether infectious or noninfectious. Here, we discuss the effect of altered immunity of gestation on a few important dermatological diseases such as psoriasis, systemic lupus erythematosus, syphilis, varicella, leprosy, and TORCH infections and vice versa.

Chorionic and amniotic membrane-derived stem cells have distinct, and gestational diabetes mellitus independent, proliferative, differentiation, and immunomodulatory capacities.

Placental membrane-derived mesenchymal stem cells (MSCs), with the advantages of being non-invasive and having fewer ethical issues, are a promising source for cell therapy. Gestational diabetes (GDM) alters the uterine environment and may affect the therapeutic potential of MSCs derived from placenta. Therefore, we evaluated the biological properties of amniotic (AMSCs) and chorionic membrane MSCs (CMSCs) from human GDM placenta in order to explore their therapeutic potential. In comparison of GDM-/Healthy- CMSCs and AMSCs, the immunophenotypes and typical stellate morphology of MSC were similar in CMSCs irrespective of disease state while the MSC morphology in GDM-AMSCs was less evident. GDM- and Healthy- CMSCs displayed an enhanced proliferation rate and tri-lineage differentiation capacity compared with AMSCs. Notably, GDM-CMSCs had a significantly increased adipogenic ability than Healthy-CMSCs accompanied by increased transcriptional responsiveness of PPARγ and ADIPOQ induction. The secretome effect of Healthy- and GDM- CMSCs/AMSCs by using conditioned media and coculture experiments, suggests that GDM- and Healthy- CMSCs provided an equivalent immunoregulatory effect on suppressing T-cells activation but a reduced effect of GDM-CMSCs on macrophage regulation. However, Healthy- and GDM- CMSCs displayed a superior immunomodulatory capacity in regulation of both T-cells and macrophages than AMSCs. In summary, we highlight the importance of the maternal GDM intrauterine environment during pregnancy and its impact on CMSCs/AMSCs proliferation ability, CMSCs adipogenic potential, and macrophage regulatory capacity.

The platelet-derived growth factor receptor alpha promoter-directed expression of cre recombinase in mouse placenta.

BackgroundNumerous pathologies of pregnancy originate from placental dysfunction. It is essential to understand the functions of key genes in the placenta in order to discern the etiology of placental pathologies. A paucity of animal models that allow conditional and inducible expression of a target gene in the placenta is a major limitation for studying placental development and function.ResultsTo study the platelet‐derived growth factor receptor alpha (PDGFRα)‐directed and tamoxifen‐induced Cre recombinase expression in the placenta, PDGFRα‐CreER mice were crossed with mT/mG dual‐fluorescent reporter mice. The expression of endogenous membrane‐localized enhanced green fluorescent protein (mEGFP) and/or dTomato in the placenta was examined to identify PDGFRα promoter‐directed Cre expression. Pregnant PDGFRα‐CreER;mT/mG mice were treated with tamoxifen at various gestational ages. Upon tamoxifen treatment, reporter protein mEGFP was observed in the junctional zone (JZ) and chorionic plate (CP). Furthermore, a single dose of tamoxifen was sufficient to induce the recombination.Conclusions PDGFRα‐CreER expression is restricted to the JZ and CP of mouse placentas. PDGFRα‐CreER mice provide a useful tool to conditionally knock out or overexpress a target gene in these regions of the mouse placenta.

An alternate surgical approach to reduce hemorrhage and complications during cesarean hysterectomy for adherent placenta

BackgroundCesarean hysterectomy for adherent placenta is associated with increased maternal morbidity due to massive hemorrhage requiring large volume blood transfusion, bladder or ureteric injury, intensive care unit (ICU) admission and prolonged hospital stay. There is an ongoing effort to improve the outcome of these women and measures to reduce blood loss. ObjectiveThe purpose of the present study was to develop an alternate surgical approach for performing a Cesarean hysterectomy in women with adherent placenta in order to reduce hemorrhage and urinary tract injuries, and thereby improve the maternal outcome. Study designA prospective observational study in a tertiary care hospital in North India. The surgical approach described in the present study was practiced in 12 women who underwent Cesarean hysterectomy for adherent placenta previa. In this approach, dissection of the bladder flap as close as to the cervix was made prior uterine incision and delivery of the baby. During dissection of the bladder flap, the blood vessels traversing between uterus and bladder were ligated and divided. ResultThese 12 women underwent Cesarean hysterectomy under general anesthesia. The interval from induction of anesthesia to delivery of the baby ranged from 40 to 79 min, and none of the babies had birth asphyxia. No woman had bladder or ureteric injury. All women had histopathological proven adherent placenta, 5 had placenta percreta, one had placenta increta and 6 had placenta accreta. The average blood loss was 1.46 l and the mean number of blood transfusions was 2.1 units. None of the women required post-operative ventilatory support or ICU admission, and all women were discharged from hospital between 4 to 7 days following Cesarean hysterectomy ConclusionThe present series describes an alternate surgical approach for Cesarean hysterectomy in adherent placenta. Dissection of the bladder flap prior to delivery of the baby followed by hysterectomy reduced the hemorrhage and there was no bladder or ureteric injury. This surgical approach requires no additional resources and may easily be followed in a low-resource setting.

The Impact of IgG transplacental transfer on early life immunity.

Pediatric vaccines have significantly reduced infectious disease-related infant mortality, but as protective immunity often require several infant vaccine doses; maternally-acquired antibodies are critical to protect infants during the first months of life. Consequently, immunization of pregnant women is an important strategy not only to protect mothers from infection, but also to provide immunity to young infants. Nevertheless, maternal immunization can also negatively impact early life immunity. In fact, maternal antibodies can interfere with the development of infant immune responses, though it is unclear if such interference is clinically significant. Moreover, the transplacental transfer of maternal immunoglobulin therapeutics can be harmful to the fetus. Thus, the risk/benefit of maternal immunization for both the mother and the fetus should be carefully weighed. In addition, it is critical to fully understand the mechanisms by which IgG is transferred across the placenta in order to develop optimal maternal and infant immunization strategies.

Examination of the twin placenta

Twin birth rates have increased dramatically over the past three decades, and twins currently account for 3% of all pregnancies. Twin pregnancies of any type are at risk for prematurity. In addition, monochorionic twin pregnancies (25–30% of all twin pregnancies) are predisposed to a specific set of complications, including twin-to-twin transfusion syndrome (TTTS), twin reversed arterial perfusion syndrome (TRAP), malformations, and intertwin growth discordance. This article reviews the basic mechanisms underlying the twinning process, the relationship between zygosity and chorionicity, and the various types of twinning. We describe the major complications of monochorionic twinning in association with their reported placental characteristics (or lack thereof). Finally, a rational, evidence-based approach to examination of the twin placenta is presented. It is essential for the pathologist to understand the value, strengths, and limitations of examination of the twin placenta in order to provide a meaningful clinicopathological correlation in complicated (monochorionic) twin pregnancies.

Clinical analysis on 30 cases of emergency obstetric hysterectomy

Objective To compare and analyze the emergency obstetric hysterectomy in the four years from January 2010 to December 2013,so as to master the surgical indications and reduce the incidence of obstetrical emergency hysterectomy.Method We retrospectively analyzed 30 patients admitted in our hospital from January 2010 to December 2013.Results Firstly,the rate of caesarean section in 2013 was obviously higher than those in 2010-2012,but the incidence of the emergency obstetric hysterectomy in 2013 didn' t go up; secondly,the main indications of emergency obstetric hysterectomy were placental factors (70％); thirdly,both the using of plugging the yarn in vagina and the usage rate of Bakri balloon in 2013 were significantly higher than those in the three years from January 2010 to December 2012,(x 2=1001.36,39.65,P=0.000,0.000); fourthly,the incidence of the emergency obstetric hysterectomy and the rate of postpartum hemorrhage in 2013 were both obviously lower those in the three years from January 2010 to December 2012 (x 2=16.56,3.26,P=0.000,0.039).Conclusion Firstly,we should prevent the occurrence of abnormal placenta in order to reduce the incidence of obstetrical emergency hysterectomy; secondly,the use of Bakri balloon could advance the success rate of the rescue of postpartum bleeding,and reduce the referral rate; thirdly,the using of plugging the yarn in vagina could reduce the rate of postpartum hemorrhage; fourthly,the lower rate of the postpartum hemorrhage and the usage of Bakri balloon both could reduce the incidence of obstetrical emergency hysterectomy. Key words: Obstetrical emergency hysterectomy; Bakri balloon; Reduce

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

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.

Distribution of Notch protein members in normal and preeclampsia-complicated placentas

Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry. In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21(Cip1) in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology.

Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches

Adverse influences during fetal life alter the structure and function of distinct cells, organ systems or homoeostatic pathways, thereby 'programming' the individual for an increased risk of developing cardiovascular disease and diabetes in adult life. Fetal programming can be caused by a number of different perturbations in the maternal compartment, such as altered maternal nutrition and reduced utero-placental blood flow; however, the underlying mechanisms remain to be fully established. Perturbations in the maternal environment must be transmitted across the placenta in order to affect the fetus. Here, we review recent insights into how the placenta responds to changes in the maternal environment and discuss possible mechanisms by which the placenta mediates fetal programming. In IUGR (intrauterine growth restriction) pregnancies, the increased placental vascular resistance subjects the fetal heart to increased work load, representing a possible direct link between altered placental structure and fetal programming of cardiovascular disease. A decreased activity of placental 11beta-HSD-2 (type 2 isoform of 11beta-hydroxysteroid dehydrogenase) activity can increase fetal exposure to maternal cortisol, which programmes the fetus for later hypertension and metabolic disease. The placenta appears to function as a nutrient sensor regulating nutrient transport according to the ability of the maternal supply line to deliver nutrients. By directly regulating fetal nutrient supply and fetal growth, the placenta plays a central role in fetal programming. Furthermore, perturbations in the maternal compartment may affect the methylation status of placental genes and increase placental oxidative/nitrative stress, resulting in changes in placental function. Intervention strategies targeting the placenta in order to prevent or alleviate altered fetal growth and/or fetal programming include altering placental growth and nutrient transport by maternally administered IGFs (insulin-like growth factors) and altering maternal levels of methyl donors.

Expression and Distribution of Notch Protein Members in Human Placenta Throughout Pregnancy

Notch signaling is an evolutionarily conserved mechanism used by invertebrates and vertebrates to control cell fates through close-range cell interactions. Four Notch receptors have been identified in vertebrates and different ligands, divided into Delta-like and Serrate-like (Jagged). Several studies have demonstrated that Notch signaling is involved in different branches of the cell fate decision tree: differentiation, proliferation and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and a correct fetal growth. Moreover, Notch and its ligands participate in the vascular remodelling and stabilization, other two processes much important and ticklish in human placenta. So, we decided to investigate the pattern of expression of Notch-1, Notch-4 and Jagged-1, together with two members related to Notch pathway and involved in angiogenesis: VEGF and p21, in human placenta during gestation by immunoblotting and immunohistochemistry. We showed a modulation of Notch proteins throughout the pregnancy; in particular we showed a slight decrease of Notch-1 throughout pregnancy, with a decreased cytoplasmic staining from the first to the third trimester of gestation in cytotrophoblast and syncytiotrophoblast. In contrast Jagged-1 showed an increase throughout pregnancy especially in syncytiotrophoblast and stroma during the third trimester of gestation. In addition, we found by immunoblotting an increase of VEGF expression from the first to the third trimester and an intense VEGF expression inside endothelial cells throughout the gestation as also confirmed by immunohistochemistry. We also showed a decrease of p21 expression during the pregnancy both through immunoblotting and immunohistochemistry assays. Moreover, we observed Notch localization in extravillous trophoblast cells that are able to invade the decidualized endometrium. Our results suggest an involvement of Notch signaling in regulation of placental cell fate decision and in angiogenesis that are dramatically important to maintain a normal physiology of this organ during pregnancy.

Poly(ADP-ribose) glycohydrolase in bovine retained and not retained placenta.

Poly(ADP-ribose) glycohydrolase (PARG) is the enzyme which degrades poly(ADP-ribose) polymers synthesized by poly(ADP-ribose) polymerase (PARP). Both enzymes are activated in response to different stimuli like oxidative stress and are involved in DNA repair processes. The retention of bovine foetal membranes (RFM) is supposed to be connected with oxidative stress conditions. The aim of the study was to detect the presence of PARG protein in bovine placenta in order to find the relationship between the process of releasing, retaining placenta and DNA repair. Placentomes, collected alter spontaneous delivery or caesarian section were divided into maternal as well as foetal part of placenta, homogenized and subjected to electrophoresis. Animals were divided into six groups as follows: A--caesarian section before term with RFM; B--caesarian section before term without RFM; C--spontaneous delivery at term with RFM; D--spontaneous delivery at term without RFM; E--caesarian section at term with RFM; F--caesarian section at term without RFM. PARG protein was detected in nitrocellulose membranes using commercially available bovine anti-PARG antibody and Western blotting technique. Single bands referred to bovine PARG standard were observed in all examined tissues as well as in human placenta used as the control of procedure. In addition, the intensity of staining was stronger in retained than properly released term placenta and in foetal than in maternal part of the placenta. These results may suggest the differences in enzyme protein content and careful conclusions can be drawn that the activities of PARG may be altered between compared groups of animals. It may confirm the presence of oxidative stress conditions and their consequences on metabolic pathways, the content of biologically active substances and processes of proper releasing placenta. Further experiments on PARG activity in bovine foetal membranes with respect to proper and improper placental release are necessary.

Evolutionary perspectives on pregnancy: maternal age at menarche and infant birth weight

We present a novel evolutionary analysis of low birth weight (LBW). LBW is a well-known risk factor for increased infant morbidity and mortality. Its causes, however, remain obscure and there is a vital need for new approaches. Life history theory, the most dynamic branch of evolutionary ecology, provides important insights into the potential role of LBW in human reproductive strategies. Life history theory's primary rationale for LBW is the trade-off between current and future reproduction. This trade-off underlies the prediction that under conditions of environmental risk and uncertainty (experienced subjectively as psychosocial stress) it can be evolutionarily adaptive to reproduce at a young age. One component of early reproduction is early menarche. Early reproduction tends to maximise offspring quantity, but parental investment theory's assumption of a quantity–quality trade-off holds that maximizing offspring quantity reduces quality, of which LBW may be the major component. We therefore predict that women who experienced early psychosocial stress and had early menarche are more likely to produce LBW babies. Furthermore, the extension of parent–offspring conflict theory in utero suggests that the fetus will attempt to resist its mother's efforts to reduce its resources, allocating more of what it does receive to the placenta in order to extract more maternal resources to increase its own quality. We propose that LBW babies born to mothers who experience early psychosocial stress and have early menarche are more likely to have a higher placental/fetal weight ratio. We review evidence in support of these hypotheses and discuss the implications for public health.

Placental-fetal Interrelationship in IUGR Fetuses—A Review

The role of placental function in maintaining an adequate fetal growth has been addressed by many different laboratories. The relationship between maternal and fetal circulation in the placenta is crucial for efficient exchanges of oxygen and nutrients. Moreover, maturational changes are taking place throughout gestation within the placenta in order to increase the transfer capacities while fetal/placental weight ratio is significantly decreasing.In human pregnancies, an impairment in the invasion of fetal trophoblast cells into the maternal decidua has been hypothesized as a cause of placental insufficiency leading to intrauterine growth restriction (IUGR). This condition has been associated with a number of adaptive changes taking place in both placenta and fetus. Adaptive changes can be followed by pathology leading to fetal death and therefore staging of the disease is fundamental for timing of delivery.A classification of the severity of IUGR in human pregnancies has been proposed based upon fetal heart rate (FHR) and Doppler velocimetry of the umbilical artery (pulsatility index or PI). This classification of clinical severity reflects different degrees of placental insufficiency and is associated with significant differences in placental nutrient exchange. Only those IUGR with pathological PI and FHR are associated with increasing degrees of hypoxemia and lacticacidemia. Furthermore, significant differences are observed in the transplacental glucose gradient in the most severe cases and the placental transport of essential amino acids is significantly reduced both in vivo and in vitro. These findings suggest that both placental metabolism and transport are altered in intrauterine growth restriction in humans.

Presence of CD30+and CD30L+Cells in Human Placenta and Soluble CD30 Levels in Cord Blood are Independent of Maternal Atopy

The intrauterine environment is characterized by a Th2 dominance during pregnancy, a milieu that also promotes atopic allergy. The aim of this study was to compare the presence of CD30, a molecule associated with Th2 related disorders such as atopic allergy, and its ligand (CD30L) in placenta in order to investigate if the placenta environment differs between atopic and non-atopic women. Serum concentrations of soluble CD30 (sCD30) from the mothers and their newborns were also elucidated. There were no differences in the immunohistochemical expression of CD30 and CD30L in placenta from atopic (n=28) compared with non-atopic (n=37) women. CD30 was expressed on the decidual stromal cells alone, while CD30L, previously not described in placenta, was detected on macrophage-like HLA-DR+cells throughout the mesenchymal chorionic villi. Serum sCD30 in atopic mothers was significantly elevated compared with serum sCD30 in non-atopic mothers (P< 0.05), while sCD30 levels in cord blood were similar in both groups independently of maternal atopic heredity. We suggest that sCD30 in cord blood and CD30 expression by decidual cells may reflect the Th2 environment surrounding the fetus, and both CD30 and CD30L could have immune regulatory functions in placenta.

The levels of lipid peroxidation products in bovine retained and not retained placenta

Unsaturated fatty acids undergo peroxidation processes. The presence of elevated levels of metabolites of lipid peroxidation processes may cause alterations in metabolic pathways which may lead to disturbances and clinical symptoms of illnesses. One such illness may be retention of fetal membranes (RFM) in cows. The aim of the study was the determination of thiobarbituric acid (TBA) reactive substances, conjugated dienes and hydroperoxides in bovine retained and not retained placenta in order to describe the oxidative status of cows affected with RFM. Placental samples were collected immediately after spontaneous delivery or caesarian section before term and at term and divided into 6 groups, with 16 animals in each group, as follows: A) caesarian section before term without RFM: B) caesarian section before term with RFM: C) caesarian section at term without RFM: D) caesarian section at term with RFM: E) spontaneous delivery at term without RFM; F) spontaneous delivery with RFM. The levels of TBA reactive substances, conjugated dienes and hydroperoxides were measured spectrophotometrically. The levels of all parameters were statistically significantly higher in the maternal than in the fetal part of placenta and the lowest in preterm groups. Statistically significantly higher concentrations in retained placenta samples than in control animals were observed. In conclusion, the metabolites of lipid peroxidation processes are elevated in cases of retained placenta and their presence might influence directly and/or indirectly the improper release of fetal membranes in cows.

Physiological roles of placental proteases in feto-placental homeostasis.

Although many proteases exist in human placenta, their physiological roles are still largely unknown. Our studies showed that these placental proteases metabolize vasoactive and immunomodulating peptides, possibly derived from the fetus, and control the exchange of peptide hormones across the placenta in order to maintain feto-placental homeostasis. We clarified the pregnancy serum oxytocinase discovered by Fekete in 1930 and angiotensinase by Page in 1947, respectively. In addition we showed bradykininase in the pregnancy serum. The ratio of peak systolic over least diastolic flow velocity of uterine or umbilical artery assessed by the Doppler technique was closely correlated with the levels of maternal serum proteases in preeclampsia, which suggested that placental proteases might control uteroplacental circulation via the regulation of concentrations of vasoactive peptides in uteroplacental circulation. Thus, changes in maternal serum protease activities were useful for monitoring of pre-elcampsia and predicting the onset of labor. The degradation of immunomodulating peptides by placental protease(s) also suggests the possible involvement of placental protease(s) in the immunological aspect of pregnancy. Recently we have cloned one of the major placental protease, oxytocinase (P-LAP). Its amino acid sequences had 87% homology of rat IRAP so called VP 165. This enzyme was confirmed to co-localize in Glut 4 containing vesicles in rat skeletal muscles and adipocytes. Accordingly PLAP, the human homologue of VP165, may have an intriguing possibility in a variety of events not restricted to the regulation of pregnancy induced phenomena.