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[The value of anatomo-pathologic examination of the placenta in areas of endemic malaria and low socio-cultural levels].

OBJECTIVES: Determine the sensitivity of the pathology examination of the placenta as a screening examination for malaria and the consequences of this infection on prematurity and birth-weight. METHODS: Eighty placentas were examined at the Mjunga, Madagascar dispensary at the beginning of the rainy season. The aspect of the placenta was compared with a malaria index and to malaria disease state as a function of parity and anti-malarial prophylaxis used by the mother as well as with the state of the infant. RESULTS: Among the placentas examined, 41.3% were considered normal and abnormal or clearly pathological in 58.7%. Estimating the gestational age on the basis of the histological examination of the amniotic cells was in agreement with the gestational age calculated from the last cycle in 53 cases and in disagreement in 8 cases. The percentage of cases of malaria discovered by the pathology examination (20%) was greater than that after thick swab screening (10%). 75% of the mothers has Plasmodium falciparum infection at the time of delivery and 13.8% of the mothers with negative thick drops had malaria lesions of the placenta. The parity of infected mothers was similar to non infected mothers. All the premature newborns had pathological placentas included 12.5% with malarial lesions. 90% of the hypertrophic newborns had pathological placentas included 50% with malarial lesions. No case of congenital malaria was observed. CONCLUSION: Pathology examination of the placenta is as sensitive as blood drop tests for screening for malaria. The histological examination of amniotic cells can give a good estimation of gestational age in developing countries.

Adolescent↗

Examination of the placenta.

A one-minute examination of the placenta performed in the delivery room provides information that may be important to the care of both mother and infant. The findings of this assessment should be documented in the delivery records. During the examination, the size, shape, consistency and completeness of the placenta should be determined, and the presence of accessory lobes, placental infarcts, hemorrhage, tumors and nodules should be noted. The umbilical cord should be assessed for length, insertion, number of vessels, thromboses, knots and the presence of Wharton's jelly. The color, luster and odor of the fetal membranes should be evaluated, and the membranes should be examined for the presence of large (velamentous) vessels. Tissue may be retained because of abnormal lobation of the placenta or because of placenta accreta, placenta increta or placenta percreta. Numerous common and uncommon findings of the placenta, umbilical cord and membranes are associated with abnormal fetal development and perinatal morbidity. The placenta should be submitted for pathologic evaluation if an abnormality is detected or certain indications are present.

Female↗

Placenta accreta: comparison of cases managed with and without pelvic artery balloon catheters.

OBJECTIVE: To describe our experience with the use of prophylactic pelvic artery balloon catheters in cases of placenta accreta diagnosed by antenatal ultrasound and to compare these cases with contemporary controls. METHODS: In this prospective study, all patients seen at our institution between January 1994 and August 1997 with the antenatal sonographic diagnosis of placenta accreta were offered prophylactic preoperative pelvic artery balloon catheterization. Patients who were delivered by cesarean hysterectomy for unsuspected placenta accreta in our institution during the same time interval served as controls. Five patients with the sonographic diagnosis of placenta accreta underwent prophylactic pelvic artery balloon catheterization. Surgical outcomes in patients who received balloon catheters were compared with those managed without them. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Five patients with placenta accreta or one of its variants were correctly identified with antenatal ultrasonography. Of the five patients who underwent pelvic artery balloon catheterization, all had placenta accreta and four required cesarean hysterectomy. The mean estimated blood loss, transfusion requirement, and length of hospitalization in patients undergoing hysterectomy managed with and without the balloon catheters was not different (P > 0.06). CONCLUSIONS: Antenatal sonographic diagnosis of placenta accreta enables preoperative planning. In our experience, use of pelvic artery balloon occlusion catheters in patients requiring a cesarean hysterectomy for placenta accreta did not improve surgical outcomes compared with patients managed without them. These preliminary findings are based on a small number of patients; therefore, further investigation is needed.

Adult↗

Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome.

OBJECTIVES: To compare early second-trimester maternal serum placenta growth factor concentrations in Down syndrome pregnancies and those in normal pregnancies. METHODS: A case-control study was performed to evaluate the maternal serum placenta growth factor concentrations in 36 Down syndrome and 320 normal pregnancies with matched gestational age during the second trimester. For the detection of serum concentrations of placenta growth factor, a quantitative sandwich enzyme immunoassay technique (R & D Systems Inc., Minneapolis, Minnesota, USA) was performed. RESULTS: Using a multiple linear regression model, maternal serum placenta growth factor level was associated with gestational age (p<0.001) and the existence of Down syndrome pregnancy (p<0.001). After converting maternal serum placenta growth factor concentrations of each analyte to multiples of the appropriate gestational median (MoM), placenta growth factor MoM (p<0.001) was revealed to be an independent variable for Down syndrome pregnancies after adjusting for the effects of maternal age (p<0.001), free beta-hCG (p<0.001) and AFP (p=0.014) by multivariate logistic regression analysis. CONCLUSIONS: Maternal serum placenta growth factor concentration was elevated in Down syndrome pregnancies during the early second trimester. Placenta growth factor might be a novel marker for maternal serum Down syndrome screening.

Biomarkers↗

Increased glycogen content and glucose transporter 3 mRNA level in the placenta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of toxic manifestations, including fetal death. In order to evaluate the effects of low-dose TCDD on placental function in this study, pregnant Holtzman rats were given a single oral dose of 800 or 1600 ng TCDD/kg body wt or an equivalent volume of vehicle (control) on gestation day (GD) 15 and the results were observed on GD16 and GD20. The number of fetal deaths increased in the animals exposed to TCDD. Although fetal and placental weight did not differ significantly between the control group and the TCDD groups, histological differences from the control rats were clearly observed in the junctional zone (JZ) of the placentas of the TCDD-exposed rats. In the control placenta, glycogen cells occupied the majority of the JZ on GD16, but then decreased in number and almost disappeared by GD20, whereas on GD20 the placenta of the TCDD-exposed rats exhibited a larger area occupied by the glycogen cells and cysts filled with eosinophilic material surrounded by glycogen cells in the JZ than that of the control group. Glycogen assay revealed that the glycogen content of the placentas from the TCDD-exposed rats was higher than in the control rats. Semiquantitative RT-PCR analysis was performed to assess the expression of glucose transporter 1 (GLUT1) and GLUT3, the two major placental glucose transporter isoforms. On GD20 the level of expression of GLUT1 mRNA in the placentas was not different between the control and TCDD groups, whereas the level of expression of GLUT3 mRNA approximately doubled in both the 800 and 1600 ng/kg TCDD groups. GLUT3 mRNA expression was restricted to the labyrinth zone of placenta, where zone-specific expression of mRNA arylhydrocarbon receptor and induction of cytochrome P450 1A1 mRNA by TCDD were observed, and none was detected in the JZ. These results, including the increase of glycogen content and GLUT3 mRNA level in TCDD-exposed placentas, provide the first evidence of alteration of glucose kinetics in the placenta by TCDD.

Animals↗

Location and activities of acetylcholinesterase and butyrylcholinesterase in the rat and human placenta.

The location and physiological functions of acetylcholinesterase and butyrylcholinesterase in the placenta are still debated. In the present study the activities of both enzymes were studied histochemically in the rat and human placenta, using an optimized Karnovsky/Roots method. Additionally, they were measured biochemically. Acetylcholinesterase was active in the syncytiotrophoblast, cytotrophoplast cells and the visceral and parietal yolk sac epithelial cells of the rat (n = 10) and in the syncytiotrophoblast, cytotrophoblast cells, endothelial cells and the media of fetal blood vessels of the human placenta (n = 9). Butyrylcholinesterase could not be detected histochemically. Biochemically measured levels at certain developmental stages of the placenta revealed maximum acetylcholinesterase activity in the 8th week p.m. human placentae (102.9 nmol.min-1 per mg protein), 35% lower activity in the 12th week p.m., and minimum (44.1 nmol.min-1 per mg protein) in term placentae. In contrast, maximum butyrylcholinesterase activity was measured in week 12 p.m. (106.9 nmol.min-1 per mg protein). In rat placentae, butyrylcholinesterase activity on gestational day 21 reached 150% of the level on gestational day 16. Acetylcholinesterase activity remained constant. In placentae of pre-eclamptic patients, acetylcholinesterase and butyrylcholinesterase activities were found to be increased by 16% and 45%, respectively. The results suggest that placental acetylcholinesterase can no longer be considered as derived from maternal blood, but is primarily located within rat and human placental tissue.

Acetylcholinesterase↗

[On the organization of the mature human placenta (author's transl)].

By means of macroscopic, histologic and enzyme histochemical methods the concept of Schuhmann and Wehler (1971) that the mature human placenta shows a morphological organization coincides with bloodflow-units was examined. The investigation deals with the existence and distribution of terminal villi which can be distinguished on the basis of histological and enzyme histochemical peculiarities. 90 placentas were available, 3 of which were premature. In 6 cases one half of the placenta or the whole organ was cut into serial sections. Mature placentas. Per dissected placenta on an average 6--7 regions with cavities in the intervillous space could be observed, which might correlate to the "placentones" postulated by Schuhmann and Wehler (1971). Using histological techniques at random scattered areas of different size of so-called "immature" villi exist in the near of the basal plate; a relation between these areas and the placentones cannot be seen. All enzymes investigated possess a lower activity in the syncytiotrophoblast of the immature villi than in the mature ones. The demonstration of phosphatases and lysosomal enzymes reveals groups of mature villi with increased activity; they form a patchy enzyme pattern. With the exception of dehydrogenases there is no relation between villi with special enzyme activities and the placentones. Premature placentas. The younger the placenta, the larger is the volume of immature villi. Result. At present a organization of the human placenta into morphological units which correlates to the bloodflow (placentones) cannot be seen. A principle of segmentation which bases on differences between the terminal villi cannot be demonstrated.

Female↗

Immunohistochemical study of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) in the human and cynomolgus monkey placenta, umbilical cord and decidua.

Tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) were studied immunohistochemically by the avidin-biotin immunoperoxidase technique in human and cynomolgus monkey placentae, membranes, umbilical cords and decidua. In early human placentae, TPA was localized mainly in the cell membranes of villous syncytio- and cyto-trophoblast. The cytoplasm of those trophoblastic cells were weakly stained with TPA. The membrane of basal chorionic trophoblast cells was strongly stained with TPA and the cytoplasm stained weakly. In early cynomolgus placentae, similar immunostaining results were obtained. However, the positive stainings for TPA was more marked in the cytoplasm of villous syncytiotrophoblast and basal chorionic trophoblast, and less marked in the cell membrane of villous cytotrophoblast. In early human and cynomolgus placentae, CA125 was not demonstrated immunohistochemically in the villi and basal chorion. In human and cynomolgus term placentae, the villous syncytiotrophoblast and basal and reflected chorionic trophoblast showed similar immunostaining as the early placentae. In addition, TPA was found in the amniotic epithelium in both sorts of placentae. TPA was not detected immunohistochemically in the umbilical cord and decidual cells. While weakly positive stains for CA125 were observed in decidual cells, CA125 was localized mainly in the membrane and cytoplasm of amniotic epithelium in both human and cynomolgus term placentae. TPA and CA125 are thus oncoplacental antigens and the monkey could serve as a model for their investigation.

Animals↗

Anaesthetic management of patients with placenta accreta.

The management of a 28-year-old primigravida with placenta accreta diagnosed during Caesarean section is described. A hysterectomy was required to control massive haemorrhage, and the patient made a full recovery. The increased incidence of placenta accreta over the last three decades is thought to be associated with the concomitant increased frequency of Caesarean section, resulting in an increased incidence of placenta praevia (1.9 per cent to 3.9 per cent). Patients with placenta praevia who have had a previous Caesarean section have a remarkably increased risk of placenta accreta. Management of placenta accreta is primarily by control of haemorrhage on delivery of the placenta. Control can be assisted by infrarenal cross-clamping of the aorta and/or intra-myometrial injection of prostaglandin F2 alpha which produces myometrial and vascular contraction. Identification of patients at increased risk, preparation for treatment and effective treatment of placenta accreta will minimize maternal morbidity and mortality.

Adult↗

Elastic fibres in the human placenta.

Recent studies described the presence of elastic fibres within stem villi of human term placenta. This particular study focuses on changes of the elastic fibre system in placental villous tree from placentas of different gestational ages. The presence of elastic fibres was researched by light and electron microscopy in first-, second-trimester and term human placentas. Light microscopic analysis revealed elastic fibres in the stroma of main stem villi and in large vessels present in the chorionic plate of term placentas. Transmission electron microscopy revealed a wide variation in microfibrillar component deposition in placentas from all the gestational ages studied. Although minimal amount of the microfibrillar component was observed only in some main stem villi of second-trimester placentas, abundant microfibrillar material was present in all types of placental villi in placental sections from term pregnancies. The amorphous component was only occasionally identified in sections from the chorionic plate of second trimester placentas. In ultra-thin sections from placental tissues from the 37th to the 42nd weeks of gestation, we can observe the amorphous component of the elastic fibres. Bundles of microfibrils with scanty participation of the amorphous component of the elastic fibres can be observed in stem villi. In mature intermediate villi, cells and their processes with distinct plasma membranes were seen close to some bundles of microfibrillar component, at times with small spots of the amorphous component. This study shows that elastic fibres of the villous stroma, are mainly composed of the microfibrillar component, while the amorphous component appears more frequently in advanced stages of villous differentiation of term placentas.

Elastic Tissue↗

The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia.

Attempts to define a pre-eclampsia susceptibility profile have been hampered by the wide clinical spectrum of the condition and the complex genetics underlying it. Genes that modulate blood pressure, fluid homeostasis and placental vascular development have been considered plausible candidates. Among these are the angiotensinogen (AGT) gene variant Met235Threo, which has been associated with pre-eclampsia and the endothelial nitric oxide synthase (eNOS) polymorphism Glu298Asp, which has been associated with both pre-eclampsia and abruptio placentae, a condition that often co-exists with pre-eclampsia. The aim of this study was to investigate a potential association between these gene variants and pre-eclampsia with and without abruptio placentae in a South African patient group. Fifty primigravidas with early onset, severe pre-eclampsia, 50 women presenting primarily with abruptio placentae (whether associated with pre-eclampsia or not) and a control panel of 50 healthy pregnant women constituted the study groups. The Met235Threo and Glu298Asp variants were characterised by polymerase chain reaction and restriction enzyme analysis. No association was demonstrated between the M235T variant of the AGT gene and pre-eclampsia or abruptio placentae. In contrast, the combined frequency of the eNOS variant genotypes (GT and TT) was significantly higher in the abruptio placentae group (49%) than the control group (21%) (p=0.006). Furthermore, in the pre-eclampsia patients who subsequently developed abruptio placentae, the eNOS GT genotype emerged as a major risk factor for the development of abruptio placentae (p<0.0001). These data suggest that the presence of a Glu298Asp eNOS variant may pre-dispose a pre-eclamptic woman to develop abruptio placentae or that it is a marker for predisposition.

Abruptio Placentae↗

Distribution of K vitamins (phylloquinone and menaquinones) in human placenta and maternal and umbilical cord plasma.

It is a well-known fact that neonatal and infantile vitamin K deficiencies cause melena neonatorum and intracranial hemorrhagic disorders. These disorders occur more frequently in breast-fed babies than in bottle-fed babies, for reasons that are still obscure. Endogenous concentrations of K vitamins (phylloquinone and menaquinones) in human placentas and in paired specimens of maternal and umbilical cord plasma were detected by high-performance liquid chromatography with fluorometric detection and postcolumn reduction. Phylloquinone (K1) and menaquinones (MK-4, MK-6, and MK-7) were found in placentas and maternal plasma. K1 and MK-4 were found in umbilical cord plasma. The experimental subjects were 13 pregnant women with normal diets (group A) and two pregnant women with diets supplemented with fermented soybeans (group B), in which MK-7 is abundant. Samples from their placentas and maternal and umbilical cord plasma were collected just after delivery. The placentas and maternal plasma of group B contained higher concentrations of MK-7 (placentas = 10.82 ng/gm and maternal plasma = 3.55 ng/ml) than did group A (placentas = 1.08 ng/gm, maternal plasma = 0.70 ng/ml). However, MK-7 was not found in umbilical cord plasma of any of the subjects. The mean K1 values of all 15 patients in placentas and maternal and umbilical cord plasma were 1.28 ng/gm, 1.54 ng/ml, and 0.11 ng/ml, respectively; mean MK-4 values were 1.18 ng/gm, 0.05 ng/ml, and 0.04 ng/ml, respectively. A high concentration of MK-4 was detected in placentas.

Adult↗

A rapid test for abruptio placentae: evaluation of a D-dimer latex agglutination slide test.

OBJECTIVE: Our purpose was to evaluate a rapid latex agglutination slide test for D-dimer, a byproduct of clot lysis, in the prediction of abruptio placentae. STUDY DESIGN: Four groups were studied: (1) 15 patients with normal pregnancies at 40 weeks' gestation, (2) 17 participants with preeclamptic pregnancies, (3) 14 patients with preterm labor, and (4) 15 patients with confirmed abruptio placentae. The latex agglutination slide test was performed with positive and negative reference solutions and plasma dilutions of 1:1, 1:2, 1:4, and 1:8. A test was considered positive if, at 2 minutes, agglutination was present at dilutions of > or = 1:2 (> or = 1.0 micrograms/ml fibrin equivalent units). Test results were compared in patient groups with and without abruptio placentae by means of the chi 2 test. RESULTS: The likelihood of a positive D-dimer test result was not significantly different among patients in the non-abruptio placentae groups (p = 0.454). Patients in the abruptio placentae group were significantly more likely to have a positive D-dimer slide test result than those in the non-abruptio placentae groups (p = 0.0001). The D-dimer test conferred sensitivity, specificity, positive predictive value, and negative predictive value of 67%, 93%, 91%, and 48%, respectively. In contrast, other laboratory measures of coagulation (e.g., platelet count, prothrombin time, partial thromboplastin time, and fibrinogen levels) yielded no better than a 20% sensitivity for abruptio placentae. CONCLUSIONS: The D-dimer slide test may be a superior rapid method to improve early diagnosis of abruptio placentae.

Abruptio Placentae↗

Preterm premature rupture of membranes and abruptio placentae: is there an association between these pregnancy complications?

OBJECTIVE: Our purpose was to determine whether the incidence of abruptio placentae is increased in pregnancies with preterm premature rupture of membranes and to assess whether certain clinical risk factors in this group predispose them to have abruptio placentae. STUDY DESIGN: A retrospective cohort study over a 2.5-year period was performed. The study group consisted of 756 singleton pregnancies between 20 and 36 weeks' gestation complicated by preterm premature rupture of membranes and managed expectantly. The control group consisted of 11,240 pregnancies not complicated by preterm premature rupture of membranes and delivered during the same time period. The incidence of abruptio placentae was compared between the two groups. The study group of patients with preterm premature rupture of membranes was further subdivided into cases with (n = 38) and without abruptio placentae (n = 718) and compared. Clinical factors such as admission amniotic fluid index, history of bleeding before or after rupture of membranes, incidence of intrapartum fetal distress, and low 5-minute Apgar scores (< 6), latency-to-delivery interval, gestational age and weight at delivery, and incidence of amnionitis and endometritis were compared. RESULTS: The incidence of abruptio placentae in the study group (38/756, 5%) was significantly higher than that in the control group (97/11, 240, 0.9%) (p < 0.001, odds ratio = confidence interval). Comparison of cases with preterm premature rupture of membranes with and without abruptio placentae demonstrated both groups to have a similar gestational age at delivery, birth weight, latency-to-delivery interval, amniotic fluid index, and infectious morbidity. The group with abruptio placentae had a significantly higher incidence of bleeding before rupture of membranes (six of 38, 15% vs eight of 718, 1%; p < 0.005) and of intrapartum fetal distress (18/38, 46% vs 49/718, 7%; p < 0.0009). CONCLUSIONS: Pregnancies complicated by preterm premature rupture of membranes that are managed expectantly are at significant risk for abruptio placentae. Preterm premature rupture of membranes in such cases is more often preceded by bleeding. These abruptions may predispose the patient to intrapartum fetal distress.

Abruptio Placentae↗

Biochemical, ultrastructural and histochemical studies of cat placentae deficient in activity of lysosomal alpha-mannosidase.

Lysosomal alpha-mannosidase activity, oligosaccharide profiles, light and electron microscopy and lectin histochemistry studies were performed on full-term placentae obtained from five litters of cats. They resulted from breeding related cats who are obligate heterozygotes for lysosomal alpha-mannosidase deficiency. alpha-Mannosidase activity in placentae from affected kittens was less than 10 per cent of control, while in placentae from presumptive heterozygotes the activity was less than 50 per cent of control. High-pressure liquid chromatographic analysis of oligosaccharides revealed massive accumulation of undegraded oligosaccharides in placentae of affected kittens. A small elevation was found in placentae from presumptive heterozygous kittens, and none was detected in placentae of normal kittens. Light and electron microscopic examinations revealed vacuolization of fetal endothelial and mesenchymal cells only in placentae of affected kittens. Succinylated wheat germ agglutinin and concanavalin A stained the fetal fibroblasts only in placentae of affected kittens.

Animals↗

Local expression of a POU family transcription factor, Pit-1, in the rat placenta.

A pituitary-specific trans-acting factor, Pit-1 regulates transcriptional activity of growth hormone (GH) and prolactin (PRL) genes. Pit-1 can bind and activate the promoters of human chorionic somatomammotropin (hCS-A) and placental GH variants (hGH-V) as well. However, expression of Pit-1 in the rat placenta has not yet been elucidated. The present study aims to determine whether the Pit-1 gene is locally expressed in the rat placenta using reverse transcription-polymerase chain reaction (RT-PCR), Northern blot and Western blot hybridization, in situ hybridization and immunohistochemistry. PCR products were further analyzed by Southern hybridization and DNA sequencing. The estimated size of Pit-1 mRNA in placenta was very similar to that in anterior pituitary (AP). PCR products from placenta were exactly the same size with that from AP and confirmed as Pit-1-specific by Southern hybridization. The Pit-1 specific sequence was also confirmed by sequencing of partial amplification fragments. Immunoreactive 33 kDa Pit-1 was present in the placenta as well as in AP. Pit-1 specific mRNA and protein were localized in the trophoblast cells of placenta. These data suggest that Pit-1 is locally synthesized in the rat placenta and may be involved in the regulation of GH- and/or PRL-like gene expression in the placenta.

Animals↗

Transfer of antivirals across the human placenta.

BACKGROUND: Viruses cross the placenta and infect the fetus. Antivirals are administered to pregnant women to protect them and the fetus against the viruses. It is necessary to know which antivirals cross the placenta and reach the fetal circulation in pharmacologically significant concentrations in order to plan antiviral therapy. AIMS: This article reviews the literature on the placental transfer of antivirals against HIV. The review considers also the placental transfer of acyclovir and ganciclovir, which are used against the herpes simplex virus and the cytomegalovirus, respectively. STUDY DESIGN: Firstly, a medline was performed with the following key words "placental transfer of antivirals". Secondly, a medline was performed with the key words "placenta transfer of..." followed by the name of a single antiviral and it was repeated for 20 antivirals. Thirdly, another medline was performed using the following key words "pharmacokinetics of antiviral in newborn" in order to collect those articles which describe in vivo transfer of antivirals. The literature was critically read and a written note was produced. RESULTS: The literature on the placental transfer of antivirals includes studies in vitro perfusing the human placenta and studies performed in vivo in which the cord and maternal antiviral plasma concentrations are compared. Both the results obtained in vitro and in vivo show that the protease inhibitors poorly transfer the placenta because of their great molecular weight. With the exception of didanosine, the nucleoside reverse transcriptase inhibitors and nelfinavir, a non-nucleoside reverse transcriptase inhibitor, cross the placenta and the cord, and maternal plasma concentrations equilibrate. CONCLUSIONS: In vitro and in vivo results are consistent with the view that the nucleoside reverse transcriptase inhibitors cross the human placenta and produce significant pharmacological concentrations in the fetal circulation. Nevirapine, the only studied non-nucleoside reverse transcriptase inhibitor, reach the equilibrium between the fetal and maternal concentration, whereas the protease inhibitors have a poor transfer across the human placenta.

Animals↗

Immunohistochemical distribution of Toll-like receptor 4 in term and preterm human placentas from normal and complicated pregnancy including chorioamnionitis.

Recently discovered Toll-like receptors (TLRs) are essential for the induction of innate immune responses. One member of the TLR family, TLR4 mediates lipopolysaccharide (bacterial endotoxin)-induced inflammatory responses. Although the innate immune system appears to be important in the pathogenesis of infection-induced preterm delivery, the distribution of TLRs in human placenta is poorly understood. Here we investigated the expression of TLR4 protein in 43 human placentas obtained from normal and complicated pregnancies delivered in the second and third trimesters, using immunohistochemistry. TLR4 was localized to the extravillous trophoblasts, intermediate trophoblasts/X cells in the degenerative villi, and villous Hofbauer cells of all preterm and term placentas examined and to the inflammatory cells in placentas with chorioamnionitis (CAM). The villous Hofbauer cells of preterm CAM placentas demonstrated increased TLR4 immunoreactivity compared with those of preterm placentas without CAM or those of term placentas with or without CAM. These results suggest an important role of the villous Hofbauer cells in the activation of innate immune system in response to infectious pathogens in preterm placentas. Elucidation of biological functions of placental TLR4 under physiological conditions requires further investigation.

Chorioamnionitis↗