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PubMed1980

Blood group Rh-D factor in human trophoblast determined by immunofluorescent method.

The chorionic villi of human placentas, 12 to 40 weeks' gestation, were examined for Rh-D blood group antigens with a direct immunofluorescent (IF) technique. Specific IF-standing was shown on the plasma membrane and cytoplasm of the villous trophoblasts. This staining decreased in intensity as the placenta matured. In addition, the trophoblasts of hydatidiform and destructive moles were also examined. The intensity of the IF-staining in these trophoblastic tumors was about the same as that in the young trophoblasts of the first trimester of pregnancy.

Fluorescent Antibody Technique↗
PubMed1984

Immunohistologic identification of trophoblast populations in early human pregnancy with the use of monoclonal antibodies.

Three murine monoclonal antibodies (H315, H316, and NDOG1) have been used in a peroxidase-antiperoxidase technique on formalin-fixed paraffin-embedded tissues to identify populations of fetal trophoblast cells by their expression of membrane antigens in chorionic and decidual tissue from the first trimester of normal human pregnancy. H315 and H316 showed comparable staining of placental villous syncytiotrophoblast and cytotrophoblast and were also able to distinguish subpopulations of nonvillous trophoblast in the placental bed, including perivascular and endovascular trophoblastic cells as well as cytotrophoblastic elements within the decidua and myometrium. H315 and H316 also showed cytoplasmic staining of columnar epithelium of endometrial glands throughout the first trimester. In contrast, NDOG1 stained chorionic syncytiotrophoblast but not villous cytotrophoblast and also did not react with any cytotrophoblastic elements in the placental bed. NDOG1 distinguished these different subpopulations of trophoblast as early as 13 to 15 days after ovulation.

Animals↗
PubMed1997

Drug actions in preeclampsia: aspirin, but not magnesium chloride or dihydralazine, differentially inhibits cultured human trophoblast release of thromboxane and prostacyclin without affecting angiotensin II, endothelin-1, or leukotriene B4 secretion.

OBJECTIVE: We hypothesized that aspirin Mg++, and dihydralazine affect the release of vasoactive agents from cultured human placental trophoblast. STUDY DESIGN: Cytotrophoblasts isolated from placentas of preterm or term deliveries of 14 healthy control women and 15 preeclamptic women were cultured in Dulbecco's modified Eagle's medium for 5 days in the presence or absence of either 0.1 mmol/L aspirin, 3 mmol/L magnesium chloride, or 136 ng/ ml dihydralazine. Vasoactive substances were quantitated by radioimmunoassay with mean +/- SEM percentage of untreated cells (= 100%) compared by the Mann-Whitney U test and analysis of variance. RESULTS: Aspirin inhibited (p < 0.01) both thromboxane and prostacyclin on days 1 and 2 in culture but not on days 3 to 5 unless the Dulbecco's modified Eagle's medium was supplemented with arachidonic acid. Aspirin inhibition was greater (p < 0.01) for thromboxane in cells cultured 24 hours after preeclamptic pregnancy (preterm 29.9% +/- 6.8%, term 20.1% +/- 5.9%) compared with normal controls (preterm 66.3% +/- 10.6%, term 68.9% +/- 11.6%). Aspirin reduced (p < 0.01) the ratio of thromboxane to prostacyclin in media of cells from preeclampsia (untreated 27.8 +/- 7.2, aspirin 13.3 +/- 4.4), but aspirin had no effect on this ratio in cultures from control normal pregnancies (untreated 6.8 +/- 2.9, aspirin 4.8 +/- 1.1). Neither magnesium chloride nor dihydralazine affected trophoblast prostanoid production, and no drug altered the media levels of angiotensin II, endothelin-1, or leukotriene B4. CONCLUSION: Aspirin selectively inhibits trophoblast prostanoid production. This inhibition depends on the availability of arachidonic acid and the presence or absence of preeclampsia. Magnesium and dihydralazine effects in pregnancy are not related to altered release of trophoblast vasoactive compounds.

Angiotensin II↗
PubMed1998

Ethanol-induced expression of cytokines in a first-trimester trophoblast cell line.

OBJECTIVES: Altered cytokine expression at the fetoplacental interface may be a potential mechanism for the development of fetal immune dysfunction in children with fetal alcohol syndrome. This study was conducted to determine whether first-trimester trophoblasts respond to ethanol exposure by the induction of specific cytokines. STUDY DESIGN: HTR-8/SVneo trophoblast cells were cultured in vitro in the presence of either ethanol (0.5% [vol/vol]), lipopolysaccharide (1 microg/mL), or ethanol and lipopolysaccharide. Expression of granulocyte colony-stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 was examined by Northern analysis and enzyme-linked immunosorbent assay. RESULTS: Culture in the presence of ethanol, lipopolysaccharide, or lipopolysaccharide and ethanol resulted in the increased transcription and secretion of granulocyte colony-stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 at significantly greater levels (P < .01) than control cultures. CONCLUSIONS: Human first-trimester trophoblasts express high levels of cytokines when cultured in the presence of ethanol. Trophoblasts may therefore be an important exogenous source of cytokines for the fetus, and altered cytokine levels during early gestation may have an adverse effect on the development of the fetal immune system.

Cell Line↗
PubMed1998

The release of 15-hydroxyeicosatetraenoic acid by human placental trophoblast is increased in preeclampsia.

OBJECTIVE: We tested the hypothesis that trophoblast produces 15-hydroxyeicosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzymatic inhibitors to determine the relative contributions of 15-lipoxygenase and the two isozymes of prostaglandin H synthase to 15-hydroxyeicosatetraenoic acid levels. STUDY DESIGN: Cytotrophoblasts isolated from placentas of normal or preeclamptic women were cultured in the presence or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosatetraenoic acid were measured by radioimmunoassay. RESULTS: When compared with normal pregnancies, cytotrophoblasts from preeclamptic pregnancies released up to fivefold higher levels of 15-hydroxyeicosatetraenoic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid, a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selective prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydroxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin. CONCLUSIONS: The data indicate that 15-hydroxyeicosatetraenoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with normal controls. Both lipoxygenase and prostaglandin H synthase contribute to 15-hydroxyeicosatetraenoic acid production, and aspirin reduces 15-hydroxyeicosatetraenoic acid secretion. We suggest 15-hydroxyeicosatetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.

Aspirin↗
PubMed1999

In vitro modulation of the expression of 15-hydroxy-prostaglandin dehydrogenase by trophoblast differentiation.

OBJECTIVE: Our goal was to determine the expression and activity of 15-hydroxy-prostaglandin dehydrogenase, a prostaglandin-metabolizing enzyme, in differentiating trophoblasts in vitro. STUDY DESIGN: Cytotrophoblasts from placentas of term healthy women were cultured in either Ham's-Waymouth medium, which hinders the process of cytotrophoblast differentiation, or medium 199, which facilitates differentiation into syncytiotrophoblasts. 15-Hydroxy-prostaglandin dehydrogenase expression was determined with Western immunoblotting, and activity was measured by a specific enzyme immunoassay of 13, 14-dihydro-15-keto prostaglandin F2 alpha, an inactive product of 15-hydroxy-prostaglandin dehydrogenase activity. RESULTS: The expression and activity of 15-hydroxy-prostaglandin dehydrogenase were enhanced during trophoblast differentiation and were higher in cells grown in medium 199 than in those grown in Ham's-Waymouth medium. 8-Bromo-cyclic adenosine monophosphate, which stimulates prostaglandin H synthase-2 expression, diminished the expression and activity of 15-hydroxy-prostaglandin dehydrogenase in concentration- and time-dependent manners. CONCLUSIONS: 15-Hydroxy-prostaglandin dehydrogenase expression and activity are regulated during trophoblast differentiation and by cyclic adenosine monophosphate. Coordinated expression of l5-hydroxy-prostaglandin dehydrogenase and prostaglandin H synthase-2 contributes to the regulation of prostaglandin release from trophoblasts.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Human trophoblast invasion and spiral artery transformation: the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction.

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance. Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR); these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR. We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.

Adult↗
PubMed2003

Cadherin-11 modulates the terminal differentiation and fusion of human trophoblastic cells in vitro.

E-cadherin and cadherin-11 are two members of the cadherin gene family of cell adhesion molecules that are differentially expressed during the aggregation, differentiation, and fusion of trophoblasts isolated from the human term placenta. E-cadherin expression is highest in cytotrophoblasts and decreases as these mononucleate cells undergo terminal differentiation and fusion. In contrast, cadherin-11 expression increases during the formation of multinucleated syncytium in these primary cultures. To define the role(s) of cadherin-11 in this developmental process, we examined the effects of ectopic cadherin-11 expression on the differentiation and fusion of JEG-3 choriocarcinoma cells, a mononucleate trophoblastic cell line. Cadherin-11 expression, but not the ectopic expression of the related cadherin subtype, cadherin-6, resulted in the formation of multinucleated syncytium in the transfected JEG-3 cell cultures. Multinucleated syncytium formation in the JEG-3 cells transfected with cadherin-11 was associated with a reduction in E-cadherin, alpha-, beta-, gamma-catenin, and p120(ctn) expression. Cadherin-11 also reduced cell proliferation and increased the levels of the mRNA transcript encoding the beta subunit of human chorionic gonadotropin, a biochemical marker of trophoblast differentiation, in these cultures. Furthermore, primary cytotrophoblasts cultured in the presence of antisense oligonucleotides specific for cadherin-11 maintained E-cadherin expression and did not undergo terminal differentiation and fusion with time in culture. Collectively, these observations demonstrate that cadherin-11 contributes to the morphological and functional differentiation of cultured mononucleate trophoblastic cells in a highly specific manner.

Cadherins↗
PubMed2003

Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and angiogenic growth factor that enhances endothelial cell invasion through the extracellular matrix (ECM). While various cell types express VEGF receptors, little is known about the biological actions of VEGF on nonendothelial cells. Therefore, the main objective of the present study was to determine the effect of VEGF on the in vitro invasiveness and proliferation of human MDA-MB-231 breast carcinoma cells and human HTR-8/SVneo trophoblast cells. Reverse-transcriptase polymerase chain reaction analysis demonstrated the presence of transcripts encoding VEGF receptors (VEGFR) -1, -2, and -3 as well as neuropilins-1 and -2 in the trophoblast cells, and the presence of transcripts encoding VEGFR-2 and neuropilins-1 and -2 in the breast carcinoma cells. Both cell lines also expressed transcripts for VEGF-A, -B, -C and -D, as well as for placenta growth factor (PlGF). Although incubation with exogenous VEGF-A(165) or VEGF-A(121) did not affect the rate of proliferation of either the trophoblast or the breast carcinoma cells, incubation with these molecules reduced their ability to invade through reconstituted ECM (Matrigel). The effect of VEGF-A(165) on the invasiveness of both cell lines was inhibited by the inclusion of a neutralizing antibody to VEGF. Exogenous VEGF-A(165) also decreased the cell surface expression of the urokinase-type plasminogen activator (a molecule required for invasion) by the breast carcinoma and trophoblast cells. These results indicate that the biological actions of VEGF on certain cell types may differ from the effects of this molecule on vascular endothelial cells, and therefore are relevant to angiogenesis-based therapies.

Angiogenesis Inducing Agents↗
PubMed2000

Interleukin-3 and human trophoblast: in vitro explanations for the effect of interleukin in patients with antiphospholipid antibody syndrome.

OBJECTIVE: To examine the effect of interleukin (IL)-3 on in vitro trophoblast differentiation, hormone production, and invasiveness affected by antiphospholipid antibodies. DESIGN: Primary cytotrophoblast cell cultures. SETTING: Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENT(S): Five normal pregnant women underwent uncomplicated vaginal delivery at 36 weeks of gestation. INTERVENTION(S): Immunoglobulin (Ig) G antibodies were isolated from the plasma of two patients with antiphospholipid syndrome and two normal control subjects with the use of protein-G Sepharose columns. Cytotrophoblast cells were dispersed in Ringer's bicarbonate buffer containing trypsin and DNAseI, filtered, and layered over a Percoll gradient in Hank's balanced salt solution. MAIN OUTCOME MEASURE(S): We investigated the effects of IL-3 and antiphospholipid antibodies on trophoblast cell invasiveness, differentiation, and hormone secretion. RESULT(S): IgG obtained from patients with antiphospholipid syndrome bound to trophoblast cells, with inhibitory effects on the cells' invasiveness, differentiation, and hCG secretion. IL-3 was able to restore in vitro placental functions. CONCLUSION(S): These results imply that IL-3 favorably affects human trophoblast implantation and development.

Antiphospholipid Syndrome↗
PubMed2003

Cytokine microenvironments in human first trimester decidua are dependent on trophoblast cells.

OBJECTIVE: To compare cytokine expression profiles of decidua basalis (containing trophoblast cells) and decidua parietalis (without trophoblast cells) for determination of microenvironments in human first trimester decidua. DESIGN: Retrospective study. SETTING: School of Medicine, RWTH University of Aachen, Aachen Germany, and Bourgognekliniek Maastricht, Maastricht, The Netherlands. PATIENT(S): Forty-six women who had undergone elective first-trimester termination of viable pregnancy at 5 to 12 weeks. MAIN OUTCOME MEASURE(S): Quantitative cytokine protein analysis in decidual tissues by enzyme-linked immunosorbent assay, qualitative cytokine messenger (m)RNA analysis in isolated decidual cell samples, and comparative mRNA and protein analysis in tissues of decidua basalis compared with decidua parietalis. RESULT(S): Interleukin-2, interferon-gamma (Th-1), interleukin-4 (Th-2), and interleukin-1beta proteins are expressed in the human first-trimester decidua. Interleukin-2, interferon-gamma, and interleukin-4 mRNA mainly derive from the decidual tissue leukocytes. Interleukin-1beta mRNA is expressed by all decidual cell types. Interferon-gamma mRNA and protein is detected predominantly in the decidua basalis, which contains trophoblast cells. CONCLUSION(S): Microenvironments are established topographically by different expression of cytokines in decidua basalis and decidua parietalis. These locally specific patterns are indicative of fetomaternal cross-talk. Higher interferon-gamma concentrations in decidua basalis may influence leukocyte differentiation (e.g., macrophage activation) and trophoblast invasion (e.g., by induction of expression of major histocompatibility complex).

Cytokines↗
PubMed2003

Human chorionic gonadotropin level as a predictor of trophoblastic infiltration into the tubal wall in ectopic pregnancy: a blinded study.

OBJECTIVE: To determine the relationship between gestational age, tubal ultrasonographic diameter, and serum hCG levels and different stages of trophoblastic infiltration of the tubal wall in ectopic pregnancy. DESIGN: Blinded prospective study. SETTING: University-based clinic in Italy. PATIENT(S): Thirty-seven consecutive patients with an ampullary ectopic pregnancy. INTERVENTION(S): Laparoscopic salpingectomy. MAIN OUTCOME MEASURE(S): Gestational age, diameter of the tubal mass as determined by transvaginal ultrasonography. and hCG level on the day of surgery. Ectopic pregnancy was classified according to the depth of trophoblastic infiltration: trophoblast limited to the tubal mucosa (stage I), extension to the tubal muscularis (stage II), or complete tubal wall infiltration up to the serosa discontinued by trophoblastic cells (stage III). RESULT(S): Fifteen patients (40.5%) had stage I tubal infiltration, 14 (37.8%) had stage II infiltration, and 8 (21.6%) had stage III infiltration. Gestational age and diameter of the tube did not differ among the three groups. The median hCG level was 1,710.5 mIU/mL (range, 113-5,635 mIU/mL) for patients with stage I infiltration. 4,690.0 mIU/mL (range, 150-21,531 mIU/mL) for patients with stage II infiltration, and 15,700.0 mIU/mL (range, 13,809-21,650 mIU/mL) for patients with stage III infiltration. All the patients with hCG levels > 6,000 mIU/mL had stage II or III invasion. CONCLUSION(S): These findings may explain why the conservative treatment of ectopic pregnancy is less successful in patients with high hCG levels than in patients with low levels. Use of radical procedures may be justified in the former group.

Adult↗
PubMed1998

Severe bleeding from peritoneal implants of trophoblastic tissue after laparoscopic salpingostomy for ectopic pregnancy.

OBJECTIVE: To describe a case of persistent trophoblastic tissue after conservative laparoscopic treatment of an ectopic pregnancy (EP). DESIGN: Case report. SETTING: University hospital. PATIENT: A 19-year-old nulliparous woman, presenting 30 days after conservative laparoscopic treatment of an EP. INTERVENTION(S): Emergency laparotomy, histologic examination of excised trophoblastic tissue, serial beta-hCG levels. MAIN OUTCOME MEASURE(S): Serum beta-hCG clearance curves after surgical treatment of an EP. RESULT(S): Histology confirmed multiple peritoneal implants of trophoblastic tissue, mainly situated on the sigmoid colon and the omentum majus. Serial beta-hCG levels decreased rapidly from 1,394 to 0 mU/L within 17 days. CONCLUSION(S): After conservative treatment of EP, patients should be followed up clinically and serial beta-hCG measurements should be obtained to ensure the absence of persistent trophoblastic tissue.

Adult↗
PubMed2001

Adjuvant hysterectomy in low-risk gestational trophoblastic disease.

OBJECTIVE: To evaluate the efficacy of adjuvant hysterectomy with chemotherapy for women with low-risk gestational trophoblastic disease. METHODS: One hundred fifteen consecutive Japanese women (16-52 years old) with low-risk gestational trophoblastic disease (46 with metastatic disease and 69 without) were treated initially with single-agent chemotherapy (etoposide in 85, methotrexate in 27, and actinomycin D in three) with or without adjuvant hysterectomy, and 97 patients (84.3%) achieved primary remission with those treatments. Eight women (9.4%) treated with etoposide required other regimens because of drug resistance or toxicities. The total dose of etoposide given to achieve primary remission was analyzed in 77 women who received etoposide alone or with adjuvant hysterectomy. RESULTS: In 34 women with metastatic disease, the mean (+/- standard deviation [SD]) total dose of etoposide was not significantly different with and without adjuvant hysterectomy (2857 +/- 842 mg versus 2815 +/- 815 mg; P =.957; Mann-Whitney U test). However, in 43 women without metastases, the total dose of etoposide was significantly less in those who had adjuvant hysterectomies than in those who did not (1750 +/- 635 mg versus 2545 +/- 938 mg; P <.05; Mann-Whitney U test). CONCLUSION: Adjuvant hysterectomy decreased the total dose of etoposide given to achieve primary remission in women with nonmetastatic, low-risk gestational trophoblastic disease. If the lesions of gestational trophoblastic disease are confined to the uterus and the woman has no desire to preserve fertility, she should be informed of adjuvant hysterectomy as a treatment option.

Adolescent↗
PubMed2002

Placental site trophoblastic tumor presenting with a pneumothorax during pregnancy.

BACKGROUND: Placental site trophoblastic tumor is a rare form of gestational trophoblastic disease that commonly presents with vaginal bleeding and amenorrhea after pregnancy. CASE: A women with a normal gestation at 37 weeks presented with a pneumothorax. The patient underwent placement of a chest tube and a subsequent thoracoscopic pulmonary bullous resection for persistence of the pneumothorax. Histological examination of the specimen revealed a metastatic placental site trophoblastic tumor. CONCLUSION: Gestational trophoblastic disease must be considered in the differential diagnosis of pneumothorax during pregnancy.

Adult↗
PubMed1997

Trophoblastic apoptosis in mice with preterm delivery and its suppression by urinary trypsin inhibitor.

OBJECTIVE: To investigate histopathologic changes of the placenta in mice with preterm delivery induced by lipopolysaccharide and the effect of urinary trypsin inhibitor. METHODS: Female C3H/HeN mice impregnated by male B6D2F1 mice were treated with lipopolysaccharide (50 micrograms/kg, intraperitoneally) or lipopolysaccharide plus urinary trypsin inhibitor (25 x 10(4) U/kg, intraperitoneally). At 3, 6, 9, and 18 hours after the second dose of lipopolysaccharide, and at delivery in the control and urinary trypsin inhibitor-treated groups, the concentrations, of interleukin-1 alpha and tumor necrosis factor-alpha were determined in serum and amniotic fluid. Subsequently, the placentas were examined. In the same manner, we examined mice treated with interleukin-1 alpha (250 micrograms/kg, subcutaneously) on day 15 of pregnancy and intact mice on days 15 and 18 of pregnancy as well as at delivery. To assess the direct action of cytokines, we cultured placental slices with tumor necrosis factor-alpha, interleukin-1 alpha, or tumor necrosis factor-alpha plus urinary trypsin inhibitor and examined them morphologically. RESULTS: Control mice were characterized by trophoblastic apoptosis and increased serum levels of tumor necrosis factor-alpha and interleukin-1 alpha. In contrast, urinary trypsin inhibitor-treated mice showed suppression of apoptosis and lower cytokine levels. Interleukin-1 alpha induced trophoblastic apoptosis and increased the serum level of tumor necrosis factor-alpha. The in vitro study showed that tumor necrosis factor-alpha directly induced trophoblastic apoptosis in placental slices. CONCLUSION: We demonstrated that trophoblastic apoptosis occurs in the placentas of a mouse model with preterm delivery induced by lipopolysaccharide. We postulated that apoptosis may lead to placental abruption, and its development may be prevented by treatment with urinary trypsin inhibitor.

Animals↗
PubMed2003

Lead enters Rcho-1 trophoblastic cells by calcium transport mechanisms and complexes with cytosolic calcium-binding proteins.

Within the placenta, a specialized Ca(2+) transport pathway develops in trophoblasts to promote growth of the fetus and hypothetically to enhance fetal uptake of Pb(2+). This hypothesis could not be tested until a method to monitor Pb(2+) influx by indo-1 fluorescence quench became available. We have applied this new method to cultured undifferentiated and differentiated Rcho-1 trophoblastic cells. Pb(2+) concentrations of 1 and 10 microM are equivalent to blood levels of 20 and 200 microg/dl in pregnant women. Over this range, Pb(2+) uptake increased with time and concentration in medium containing 1 mM Ca(2+) but was greater in Ca(2+)-omitted solutions. Activation of capacitative Ca(2+) entry (CCE) with thapsigargin, an endoplasmic reticulum (ER) Ca(2+) pump inhibitor, increased Pb(2+) uptake, while inhibition of CCE by La(3+) decreased influx. Parathyroid hormone-related peptide (PTHrP) stimulates the synthesis of Ca(2+)-binding proteins (CaBPs), as well as Ca(2+) transporters, during trophoblastic differentiation. Pretreatment for 72 h with PTHrP increased Pb(2+) uptake by undifferentiated Rcho-1 cells but had little effect on the quench in differentiated cells, probably due to their greater content of CaBPs which competed for Pb(2+)-binding with indo-1. This competition was most evident in differentiated cells when 1 microM Pb(2+) caused an initial quench, followed by a rise in fluorescence. This rise was not inhibited by thapsigargin, thereby ruling out sequestration into the ER and leaving complexation of Pb(2+) by CaBPs as the most plausible interpretation. We conclude that trophoblasts have the ability to clear Pb(2+) from the maternal circulation and deliver it to the fetus.

Animals↗
PubMed2003

Transmission of HIV-1 infection between trophoblast placental cells and T-cells take place via an LFA-1-mediated cell to cell contact.

HIV-1 vertical transmission is thought to mainly take place by virus crossing the placental barrier. However, the mechanism by which HIV-1-infects placental cells remains to be elucidated. We have found that purified cytotrophoblasts as well as trophoblastic cell lines are susceptible to infection by different HIV-1 isolates as detected by DNA-PCR and release of infectious virus, although with very low efficiency. Purified trophoblast or trophoblastic cell lines express low levels of chemokine receptors CCR-5 and CXCR-4 but not CD4 on the cell surface. To test if those molecules were used as receptors for HIV-1 infection, placental cells were pretreated with antibodies to CD4, CC-chemokines, C-X-C chemokines. None of those treatments inhibited HIV-1 infection. In contrast, we have found that HIV-1 infection of placental cells was increased in cocultures of infected T-cell blasts and placental cells. More interestingly, antibodies to beta(2) integrins and to LFA-1 were able to significantly block infection of placental cells. Cell surface expression of ICAM-1, an adhesion molecule involved in attachment of leukocytes to placenta, was upregulated in HIV-1-infected placental cells. Placental cells were able to transfer HIV-1 infection to T-cell blasts. This transmission required cell to cell contact and was also inhibited by anti-LFA-1 antibodies. In summary our results suggest that placental trophoblast could be infected by HIV-1 by a mechanism involving T cell to placental contact. Moreover, placental infection enhanced ICAM-1 expression and leukocyte adherence, an event which was required to transfer HIV-1 infection to T cells. This provides an explanation of the virus passing through the placental barrier during in utero HIV-1 vertical transmission.

CD4 Antigens↗