Serum- and cell-mediated immune protection of mouse placenta and fetus against a Brucella abortus challenge: expression of barrier effect of placenta

When mice are intravenously inoculated with a virulent Brucella abortus strain at day 12 to 14 of pregnancy and killed three to five days later, colonization of placentae, fetuses and spleens can be estimated by the frequency and level (bacterial count) of infection and by linkage between individual placental and paired fetal infections. This linkage indicates the placental barrier effect, defined as the number of non-infected fetuses linked to 100 colonized placentae. Immune mice serum raised against two Brucella fractions injected one day before challenge (1) restricted the placental colonization (the dose required to infect 50 per cent placentae was increased by 50 to 70 times compared to controls), (2) decreased the level of splenic and placental infection, and (3) increased the barrier effect so that most fetuses were protected even when linked to a heavily infected placenta. Immune (B + T) spleen cells from mice vaccinated with a Brucella cell-wall fraction transferred to recipients seven to eight days before mating, that is, 22 days before challenge (1) restricted the frequency of placental and fetal colonization, (2) decreased the level of splenic, placental and fetal infections, and (3) increased the barrier effect. However, separated B- and T-cells were less active, in particular on the level of fetal infection. In contrast with serum, the cells did not decrease infection of the fetuses linked to heavily infected placentae.     

Protection of murine gestational tissues from picornavirus infection in the preimplantation period

Mice were inoculated with Theiler's murine encephalomyelitis virus (TMEV) on gestational days 1-3 (pre-implantation) or days 4-5 (peri- or post-implantation) or with control cell lysate (days 1-5). Dams were subsequently sacrificed between days 11-14 of gestation, and placentae and fetuses were harvested. Few placentae from dams inoculated with virus on days 1-3 were positive by virus culture (2 per cent) or in situ hybridization (6 per cent), and no fetuses were positive by either technique. In contrast, most placentae from dams inoculated with virus on days 4-5 were virus-positive by culture (96 per cent) or in situ hybridization (100 per cent), and a moderate number of fetuses were also positive (30 per cent by culture, 19 per cent by in situ hybridization). Necrosis was present more frequently in placentae from mice inoculated with virus on days 4-5 (55 per cent) than in placentae from dams inoculated with virus on days 1-3 (19 per cent) or with control cell lysate (18 per cent). Viral infection, mononuclear inflammation and cell necrosis were identified in the heart and great vessels of TMEV-infected fetuses. These results indicate that gestational tissues are largely protected from viral infection before implantation. After implantation, gestational tissues are more readily infected and damaged by maternal picornavirus infection.     

Morphological aspects of the placenta in HIV pregnancies

Forty-nine placentae from HIV-seropositive mothers were collected in various hospitals in France and Belgium. Twenty [corrected] placentae with seven fetuses from interrupted pregnancies and 29 [corrected] placentae from spontaneous deliveries, including two stillborns and a set of twins, were studied morphologically. No significant abnormalities were observed in the aborted material. The placentae corresponding to deliveries presented no significant gross abnormalities but the ratio of fetal to placental weight was significantly decreased in the study group compared with the control group (6.13 versus 7.41; P less than 0.001), associated with a congestive and mature aspect of the parenchyma. Histologically a high incidence of chorioamnionitis (43 per cent) was found, contrasting with the absence of villitis. A relative villous hypercellularity was observed in the study group compared with the control group. Ultrastructural studies of 13 placentae corresponding to gestations of 10 to 40 weeks are presented. In six cases, retrovirus-like particles were found at various sites, such as villous fibroblasts, syncytiotrophoblast and endothelial cells, and in the free membranes.     

Detection of rubella virus in fetal and placental tissues and in the throats of neonates after serologically confirmed rubella in pregnancy

From 35 therapeutic abortions performed because rubella had occurred at 2-19 weeks of pregnancy, 120 fetal organs, 12 specimens of mixed products of conception, and 15 placentae were tested for rubella virus. Virus was isolated from 10 out of 11 fetuses (91 per cent) from women infected at 2-8 weeks, from 5 out of 8 (63 per cent) infected at 9-10 weeks, and from 2 out of 16 (13 per cent) infected at 11-19 weeks. Hybridization tests for viral RNA on 39 fetal organs from eight cases revealed infection in four additional fetuses. Virus was isolated from only 3 out of 15 aborted placentae, but hybridization tests on six placentae revealed infection in three additional specimens. Hybridization was superior to virus isolation for detecting rubella infection in products of conception and is therefore potentially the better method for examining chorionic villus biopsies. Rubella virus was isolated from the throats of 4 out of 9 infants (44 per cent) infected during the first 12 weeks of gestation, but from none of 13 infected after 17 weeks. Infants in the latter group are unlikely to infect susceptible contacts.     

The effects of unilateral ovariectomy during pregnancy on placental and fetal growth in mice

A comparison between placental weight and number of fetuses in normal mice and those in mice unilaterally ovariectomized on the sixth day of pregnancy, revealed a relative hypertrophy of the placentae of the latter group, with a predominance of the effect in litter sizes of five or less. The weights of the fetuses in the unilaterally ovariectomized group were not significantly different from those of the controls, thus affording no evidence of a causal connection between fetal weight and gross placental weight.     

Fetal and maternal blood volumes in shed human placentae: discrepant results comparing morphometry to haemoglobin content

The maternal blood volume (MBV) and fetal blood volume (FBV) of shed human placentae delivered by caesarean section at term were measured using a morphometric technique and from the placental content of adult and fetal haemoglobin. MBV was 35.3 +/- 1.5 (s.e.m.) per cent by the former and 11.0 +/- 1.5 per cent by the latter technique. FBV was 11.0 +/- 0.7 and 9.0 +/- 0.6 per cent respectively (n = 6). Measurement of the dimensions of individual villi initially photomicrographed in 0.9 per cent NaCl and subsequently re-photographed in fixative suggested that individual villi shrank to 0.7 of their initial volume during fixation. It is suggested that morphometric measurement of MBV may lead to approximately a threefold overestimate because of relative MBV expansion and villous tissue shrinkage during the process of fixation without alteration in overall placental volume.     

Fetal pathology in human parvovirus B19 infection

In a current Netherlands study on the effects on mother and child of infection with the human parvovirus B19 during pregnancy, 10 pregnancies have been reported. Three of them ended before term: two in fetal death and one by elective abortion. In two of these fetuses B19 infection in cells other than those of the erythroid series was demonstrated, and in the one terminated, ocular malformation and extensive inflammatory reactions in all fetal and placental tissues were found. The presence of B19 DNA was demonstrated by dot hybridization in placental and fetal tissues. In the third no gross fetal abnormalities were found, although B19 DNA was detected in several fetal tissues by in-situ hybridization. Of the remaining seven pregnancies, six ended at term in the birth of apparently healthy babies. The other child was born near term with a low birthweight and multiple congenital malformations, but with no proof of intrauterine B19 infection. It is concluded that B19 infection in pregnancy can interfere with organ development and may lead to intrauterine fetal death.     

Fetal pathology in human parvovirus B19 infection

Summary. In a current Netherlands study on the effects on mother and child of infection with the human parvovirus B19 during pregnancy, 10 pregnancies have been reported. Three of them ended before term: two in fetal death and one by elective abortion. In two of these fetuses B19 infection in cells other than those of the erythroid series was demonstrated, and in the one terminated, ocular malformation and extensive inflammatory reactions in all fetal and placental tissues were found. The presence of B19 DNA was demonstrated by dot hybridization in placental and fetal tissues. In the third no gross fetal abnormalities were found, although B19 DNA was detected in several fetal tissues by in-situ hybridization. Of the remaining seven pregnancies, six ended at term in the birth of apparently healthy babies. The other child was born near term with a low birthweight and multiple congenital malformations, but with no proof of intrauterine B19 infection. It is concluded that B19 infection in pregnancy can interfere with organ development and may lead to intrauterine fetal death.     

RU 486 induced suppression of placental neutrophil elastase inhibitor levels

After administration of RU 486 to pregnant cynomolgus monkeys, placental morphology varied from normal to pathological. In all cases (n = 5) circulating and placental PAPP-A levels were markedly suppressed by 76.0 per cent and 55.5 per cent, respectively. When fetal demise occurred within 24 h prior to caesarian section, morphological changes consistent with an active inflammatory (polymorphonuclear leukocytosis) reaction was readily observed at the utero-placental interface, degrading the chorionic villi. Whereas heparin-Sepharose fractionated aqueous extracts of placentae inhibited human neutrophil (or granulocyte) elastase (HGE) activity, extracts of placenta being degraded by host phagocytic-proteolytic defense system were rich in HGE activity. This study establishes: (1) the cynomolgus monkey as a model for PAPP-A studies, (2) that haemochorially implanted placentae produce PAPP-A, a heparin-binding inhibitor of HGE, (3) that administration of progesterone receptor antagonist suppressed placental PAPP-A synthesis, and (4) disrupted protease-protease inhibitor equilibrium at the feto-maternal interface. Thus supporting a role for progesterone in placental PAPP-A production and maintenance of a placental barrier against maternal phagocytic-proteolytic defenses.     

Glucocorticoid regulation of placental breast cancer resistance protein (Bcrp1) in the mouse

Placental breast cancer resistance protein (Bcrp1; encoded by the Abcg2 gene) limits maternal-fetal transplacental transfer of numerous endogenous and exogenous substrates; however, the regulation of placental Abcg2 and Bcrp1 and is not well understood. Placental Abcg2 messenger RNA (mRNA) levels decrease with advancing gestation in the mouse, and this corresponds to increasing levels of maternal and fetal plasma glucocorticoid. Glucocorticoids, including dexamethasone (DEX), downregulate Bcrp1 expression and function in both breast cancer cell lines and the blood-brain barrier in vitro; whether this occurs in the placenta is not known. The potential regulatory role of synthetic glucocorticoids on placental Bcrp1 is of interest, given that approximately 10% of pregnant women are treated with synthetic glucocorticoid for threatened preterm labor. We hypothesized that (1) exposure of pregnant mice to DEX will downregulate placental Abcg2 mRNA and Bcrp1 protein, and (2) results in increased fetal accumulation of [(3)H]mitoxantrone. Pregnant mice were treated with DEX (low-dose: 0.1 mg/kg or high-dose: 1 mg/kg) or vehicle (saline) from embryonic day (E) E9.5 to E15.5 or E12.5 to E18.5. In placentae derived from female fetuses, high-dose DEX significantly downregulated Abcg2 mRNA expression on E15.5 (P < .05) and significantly inhibited Bcrp1 function (P < .05). Similarly, high-dose DEX significantly inhibited Bcrp1 function in the placentae derived from male fetuses (P < .05). In conclusion, there is a dose-dependent regulatory effect of synthetic glucocorticoid on placental Abcg2 mRNA and Bcrp1 function in vivo. Further, it appears that, at the level of Abcg2 gene expression, the female-derived placentae are more susceptible to the effects of DEX than male placentae.     

A role for maternal serum screening in detecting chromosomal abnormalities in fetuses with isolated choroid plexus cysts: a prospective multicentre study.

A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.     

Chromosomal prenatal diagnosis: study of 936 cases of intrauterine abnormalities after ultrasound assessment

Nine hundred and thirty-six prenatal chromosomal analyses were performed by four cytogenetic centres after ultrasound diagnosis of fetal abnormalities, amniotic fluid disorders, fetal growth retardation, and fetal or placental abnormalities. During the same period, 6515 fetal karyotypes were analysed because of maternal age. Frequencies of chromosomal aberrations in each case were respectively 4.4, 6.7 and 15.8 per cent, compared with 3.18 per cent when the fetal karyotype was performed because of maternal age. High rates of chromosomal aberrations are observed in cases of cervical hygroma, limb abnormalities, omphaloceles, duodenal stenosis, hydrocephalus, and facial abnormalities. In the case of polymalformations, this rate was 29.2 per cent. When malformations were seen together with an amniotic fluid disorder or growth retardation, 21.5 per cent chromosomal aberrations were observed. This frequency was 10.4 per cent when growth retardation was associated with an amniotic fluid disorder. Trisomy 13, 18, 21 and monosomy X accounted for 4/5 of all abnormalities in which we observed a high rate of triploidies (4.9 per cent) and balanced (3.3 per cent) or unbalanced (9.8 per cent) non-Robertsonian structural abnormalities. Sonographic ascertainment of these aberrations and prenatal characteristics of major anomalies are discussed.     

The effect of a reversible period of adverse intrauterine conditions during late gestation on fetal and placental weight and placentome distribution in sheep

Adverse intrauterine conditions occurring during early to mid-gestation or throughout the whole of gestation influence placental weight and the distribution of placentome types in sheep. However, no study to date has investigated the effect of a reversible period of adverse intrauterine conditions during late gestation upon fetal and placental weight and placentome distribution in sheep. Twenty-two sheep fetuses were chronically instrumented with an inflatable cord occluder, amniotic and vascular catheters and with a Transonic flow probe around an umbilical artery. At 125 days (term isca.145 days) the occluder was inflated to reduce umbilical blood flow by ca.30 per cent for 3d in 12 fetuses (umbilical cord compressed, UCC). The occluder was then deflated and umbilical blood flow allowed to return to baseline. The remaining 10 fetuses acted as sham-operated controls in which the occluder remained deflated at all times. At 135-137dGA ewes were humanely killed and tissues collected, weighed and placentomes classified. A reduction in umbilical blood flow by approximately 30 per cent from baseline for 3 days in UCC fetuses led to mild fetal asphyxia throughout the period of cord-compression. After deflation of the occluder cuff, umbilical blood flow returned to a level that was significantly greater than that measured during baseline. Umbilical cord compression had no effect on fetal body weight but significantly increased fetal adrenal weight relative to body weight. While the total number of placentomes was not altered by cord-compression, total placentome weight and the total weight of C/D-type placentomes were both reduced in UCC relative to control placentae. In addition, the mean weight of placentomes, and of C/D-type placentomes specifically, was significantly lower in UCC relative to control placentae. When expressed as a percentage of the total number of placentomes in the placenta, there was a significantly lower percentage of C/D-type placentomes in UCC relative to control placentae. In addition, there was a significant relationship between the total number of placentomes and the percentage C/D-type placentomes in control, but not UCC, placentae. The data suggest that a temporary, reversible period of adverse intrauterine conditions occurring late in gestation in sheep has persisting effects upon the placenta, mean placentome weight and placentome distribution.     

斑点核酸杂交技术检测胎儿巨细胞病毒感染的研究

用￣３２Ｐ标记的巨细胞病毒（ＣＭＶ）探针通过斑点核酸杂交技术，对胎盘、脐血及胎儿组织中的ＣＭＶＤＮＡ进行了检测。结果表明，死胎、胎儿畸形的５２份胎盘组织及４８份胎肾组织中ＣＭＶＤＮＡ阳性者分别为４份及５份，正常好妊娠组（早、晚期人耳流产与足月产）的７７份胎盘及３２份胎肾组织中ＣＭＶＤＮＡ均为阴性，同一病例胎盘与胎肾组织中ＣＭＶＤＮＡ均阳性者３例。２例畸形胎儿脐血白细胞中ＣＭＶＤＮＡ阳性者１例，另一例胎儿畸形脑组织及腮腺组织中ＣＭＶＤＮＡ阳性，而正常足月产的２４例脐血白细胞中ＣＭＶＤＮＡ均阴性。共诊断８例胎儿感染ＣＭＶ，正常妊娠组无１例胎儿感染ＣＭＶ，从分子水平上证实ＣＭＶ是致死胎与胎儿畸形的重要病原。     

Toxemia of pregnancy: assessment of fetal distress by urinary estriol and circulating human placental lactogen and alpha-fetoprotein levels.

The efficacy of three biochemical methods for the detection of fetal distress was assessed in a prospective study of 224 singleton pregnancies complicated by toxemia. Fetal distress was diagnosed in 65 cases (29 per cent). Abnormally low urinary estriol (E3) excretion pointed out 63 per cent, low serum levels of human placental lactogen (HPL) 27 per cent, and elevated maternal serum alpha fetoprotein (AFP) 10 per cent of distressed fetuses. The efficacy of each test increased with the severity of maternal disease. The frequencies of false pathologic levels were: E3 19 per cent, HPL 0 per cent, and AFP 1 per cent of the cases with a normal fetal outcome. Although E3 was by far the most effective marker, abnormal levels of HPL and AFP provided supportive evidence for fetal distress by pointing out those cases in which E3 reading was not a false positive.     

SHORT COMMUNICATION Maternal Thyroid Dysfunction and c- Fos and c- Jun Expression in Rat Placenta

Maternal thyroid dysfunction is associated with perturbed fetal brain development and neurological deficits in adulthood in rat and human. To investigate whether these effects occur secondary to placental dysfunction, c- fos and c- jun expression in placenta from normal (euthyroid) and moderately hypothyroid rat dams were investigated by Northern hybridization analysis.In normal placenta, c- fos expression increased by 74 per cent between 16 and 21 days of gestation (dg) whereas c- jun expression declined by 46 per cent. Moderate maternal hypothyroidism depressed placental c- fos expression by 32 per cent at 19 dg, but elevated c- fos and c- jun expression by 139 and 86 per cent, respectively, at 21 dg. Maternal hypothyroidism may therefore induce c- fos/c- jun -related placental dysfunction, but only relatively late in gestation when fetal thyroid function is already established.     

Evaluation of the Xe-133 clearance method for indirect placental blood flow determination

The Xe-133 clearance method, chosen by several groups for indirect placental blood flow (PBF) determination, is evaluated using a placenta-fetus compartment model first introduced by Moll (1973). The placenta is modelled as a strong concurrent, counter-current or cross-current exchange system. The fetal circulatory system is simplified by dividing it into two major branches: the umbilical circulation and the fetal tissue or systemic circulation. Following an arbitrary labelling of maternal arterial blood, Xe-133 concentrations in myometrium, placenta and fetus are derived from the model and are used to calculate placental clearance rates. The dependence of clearance rates on maternal and fetal PBF, on the distribution of fetal cardiac output, and on the effect of recirculation times, is considered in the three different arrangements of maternal and fetal placental vessels.     

Sonographically thick placenta: a marker for increased perinatal risk--a prospective cross-sectional study

The aim of this study was to determine placental thickness by ultrasound examination throughout pregnancy and establish the correlation of sonographically thick placenta with perinatal mortality and morbidity.Placental thickness was determined by routine sonographic examination throughout pregnancy in 561 normal singleton pregnancies. Thick placenta was determined as placenta that was above the 90th percentile. Gravidae between 20-22 weeks' gestation (n=193) and 32-34 weeks (n=73) were then divided into two groups according to placental thickness. The study group consisted of 44 gravidae with thick placenta. The control group included 151 gravidae with placental thickness between the 10th and 90th percentile. A comparison of perinatal mortality and morbidity rates as well as the incidence of small and large for gestational age neonates was conducted.A linear increase of placental thickness was found to correlate with gestational age throughout pregnancy. No statistical differences were observed between the two groups with regard to obstetrical variables such as maternal age, parity and gestational age at delivery. No correlation was found between placental thickness and maternal age or parity. The incidence of perinatal mortality was significantly higher among gravidae with thick placentae (6.82% versus 0.66 per cent, P=0.037, 95 per cent confidence interval 1.71-70.29). Birthweight at term was found to be above 4000 g in 20.45 per cent of the thick-placenta group as compared to 5.3 per cent in the control group (P=0.001, 95 per cent CI 2.08-13.85), and birthweight of less than 2500 g was found in 15. 9 per cent of the thick-placenta group as compared to 7.3 per cent in the control group (P=0.03, 95 per cent CI 1.11-8.14). The incidence of fetal anomalies was 9.1 per cent in the thick-placenta group and 3.97 per cent in the control group (not significant). Sonographically thick placenta is associated with increased perinatal risk with increased mortality related to fetal anomalies and higher rates of both small for gestational age and large for gestational age infants at term.     

Leptin secretion to both the maternal and fetal circulation in the ex vivo perfused human term placenta

The contribution of placental leptin, if any, to both the fetal and maternal circulation and its role in pregnancy remains to be determined. In an experiment to investigate this, 27 placentae from term pregnancies were perfused ex vivo (gestational age=39.5 s.d. 1.2; range=38-42 weeks: fetal weight=3285 s.d. 482; range=2480-4420; birthweight centile range=4th to the 98th) at both the maternal and fetal interface. Placental leptin was exported into both the maternal and fetal circulations. The log leptin production by the maternal side of the placenta was significantly greater (P=0.001) than that for the fetal side (5.193 s.d.1.049 versus 4.387 s.d. 0.768 ng/placenta/min). There was no significant relationship between maternal and fetal log leptin production and maternal body mass index, birthweight, birthweight centile, ponderal index or gestational age or with cord blood pO(2), pCO(2) and pH. There was however, a significant increase in the maternal log leptin production with increasing fetal to placental weight ratio (P=0.017; r(2)=20.7 per cent) but no corresponding relationship for fetal leptin production. It is proposed that such a mechanism would allow the placenta to modulate fat supply to the fetus in response to the fetal demand relative to placental supply.     

Enterovirus associated placental morphology: a light, virological, electron microscopic and immunohistologic study.

The purpose of this study was to identify the possible effect of enteroviruses on placental tissue. Seventy-eight pregnant women were studied throughout their pregnancy: enteroviral infection was detected by faecal viral isolation and seric neutralization of previously identified virus in cell culture. In 19 cases of confirmed maternal infection, placentae were examined grossly, by optical microscopy, immunohistochemical and electron microscopic methods. Ten term placentae from women included in the study, with no clinical, serological or virological evidence of enteroviral infection, were used as control, and examined by gross and optical microscopy. In 17 specimens (echovirus-coxsackievirus) an haematogenous placentitis was suspected on the basis of gross observation. Microscopic lesions were similar to those found in other viral infections, with specific features. The nature of the inflammatory reaction pointed to the presence of an acute type of haematogenous placentitis, not present in placentae of the control group. The authors (AA) comment on the results and present the hypotheses about the available data: (1) maternal enteroviremia and faecal virus shedding without placental invasion, placentary damage being an unspecific consequence of infection; (2) direct virus-induced injury is not the only possible cause for the lesions: (3) placental enteroviral infection occurred with placental pathology but the virus did not cross the organ as the newborn had no signs of infection.