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Mosaicism confined to placenta in pregnancies with adverse outcome.

Chorionic villi and fetal tissues from 50 pathological human conceptions at gestational weeks 9-40 were cultured and cytogenetically analyzed to explore the existence of chromosomal mosaicism confined to the extraembryonic tissues and to clarify the relationship between confined placental mosaicism and adverse outcome of pregnancy. Chorionic villi and fetal tissues from 12 second trimester gestations terminated for social reasons served as a control group. In two pathological gestations, true mosaicism was found exclusively in chorionic cells and could not be confirmed in cells derived from the fetal tissues. One of these was severely growth retarded. Concordant results were obtained in all other cases.

Abortion, Induced↗

[Prenatal diagnosis using chorionic biopsy in the 1st trimester of pregnancy].

One hundred-sixteen pregnant women were subjected to chorionic villi sampling at the gestational age of 8-11 weeks. In 12 cases, the transabdominal approach was used, and in the rest of the cases, a flexible catheter was placed transcervically. The most frequent indication was the age of the pregnant women (over 35). Chorionic villi sampling was successfully performed in 97.5% of cases. Fetal loss amounted to 1.9%.

Adult↗

Villous papyraceous: an unusual cause of tamoxifen-induced postmenopausal bleeding.

OBJECTIVE: We describe an unusual histological finding in a woman with postmenopausal bleeding who was being treated with tamoxifen for breast cancer. METHOD: This patient presented with a history of postmenopausal bleeding, 4 years after her last period. Pelvic ultrasound showed a thickened cystic endometrium and bulky uterus. A diagnostic endometrial aspiration biopsy by Pipelle was performed; at this time, urinary beta-human chorionic gonadotropin was negative. RESULTS: Histology showed villous papyraceous (sclerosed and mummified chorionic villi) in a background of scanty atrophic endometrium. CONCLUSION: Tamoxifen has dual estrogenic and antiestrogenic effects; the estrogenic effects have been associated with ovulation induction in premenopausal women. This effect, however, has not been documented in postmenopausal women. We conclude that the presence of chorionic villi is, in this instance, likely to be a tamoxifen-mediated effect.

Antineoplastic Agents, Hormonal↗

Genetic diagnosis in multiple pregnancies.

A twin gestation presents unique problems in both genetic counseling and prenatal diagnosis. This article describes the specific genetic counseling concerns for a twin gestation and outlines the available techniques for genetic prenatal diagnosis. The technical aspects, risks and benefits to the pregnancy of amniocentesis and of chorionic villi sampling are compared. Although the risk of miscarriage after amniocentesis in a twin gestation is at least double that for a singleton, much of this additional risk is secondary to the inherent hazards of twins and not procedure-related. In experienced centers, chorionic villi sampling is equally safe and efficacious, and allows an earlier diagnosis that may be beneficial when discordant results are found. The aspects of serum screening unique to twin gestations are also outlined. Prenatal diagnosis by both chorionic villus sampling and amniocentesis can be safely performed in twin gestations and higher-order multiple gestations. Serum screening is also useful, but appears to have a lower sensitivity and specificity than in singletons.

Amniocentesis↗

Comparative studies on the distribution of binucleate cells in the placentae of the deer and cow using the monoclonal antibody, SBU-3.

A monoclonal antibody SBU-3 raised against an antigen expressed by the binucleate cells in the trophoblast of the sheep placentome crossreacts with an antigen expressed by binucleate cells in the placenta of the deer and the cow. This monoclonal antibody has been used to study the distribution of this subpopulation of binucleate cells in the deer and cow during fetal development. In the deer at less than 30 days of gestation, SBU-3-positive binucleate cells were observed in the trophoblast of the chorionic villi and in the trophoblast at the interplacentomal areas. With the advancement of pregnancy, the placentome increased in size and SBU-3-positive binucleate cells were observed to localise mainly at the tips of the chorionic villi and were arranged in clusters. There was evidence of SBU-3-positive binucleate cell migration into the epithelium of the caruncular crypt, but there was no fusion of migrated cells to form a syncytial layer. Such a pattern of SBU-3-positive cell distribution was seen up to 95 days of gestation, the oldest placenta available for study. In the cow at 28-34 days of gestation, SBU-3-positive binucleate cells were seen in the trophoblast located in close apposition to the caruncular epithelium. From 35-240 days, there was an increase in the number of SBU-3-positive binucleate cells in the placentomal trophoblast. As in the deer, SBU-3-positive binucleate cells migrated into the epithelium of the caruncular crypt, and these cells did not fuse to form a syncytial layer. By 241-283 days, SBU-3-positive binucleate cells present in the placentomal trophoblast were stained less intensely. Many of the binucleate cells which had migrated into the epithelium of the caruncular crypts had pyknotic nuclei and scanty cytoplasm containing weakly stained SBU-3-positive product. It is concluded that the monoclonal antibody SBU-3 recognises an antigen common to ruminants which is expressed only by binucleate cells in the placenta. In the deer and the cow, granule transfer seems to be the primary function of binucleate cell migration. The histological classification of the mature placenta of the deer and the cow is epitheliochorial.

Animals↗

[Complications of the invasive prenatal diagnostic methods].

OBJECTIVE: To provide a literary overview of the complications associated with the invasive prenatal diagnostic methods in the 1st and 2nd trimester of pregnancy. DESIGN: A summarising article. SETTING: Mother and Child Care Institute, Prague. METHODS: Compilation of data from professional literature. RESULTS AND CONCLUSION: The global trend is characterised by the effort to move prenatal diagnostics into the period of the first trimester. The invasive diagnostic methods of this period - sampling of chorionic villi and timely amniocentesis are subjects of a number of discussions, which deal primarily with their reliability and safety. The main indicator is the evaluation of foetal losses occurring in connection with the action. So far, the safest method is second-trimester amniocentesis; for early diagnostics, the trans-abdominal sampling of chorionic villi is preferred to transcervical one and to early amniocentesis.

Amniocentesis↗

Characteristics of L-ornithine: 2-oxoacid aminotransferase and potential prenatal diagnosis of gyrate atrophy of the choroid and retina by first trimester chorionic villus sampling.

A deficiency of the mitochondrial matrix enzyme L-ornithine: 2-oxoacid aminotransferase causes gyrate atrophy of the choroid and retina with hyperornithinemia (MIM 258870), a blinding degenerative disease, which is inherited as an autosomal recessive trait. We have developed a sensitive microradioisotopic method for enzyme assay by using 2-oxo-[5-14C] glutarate as the substrate and performing the separation of the product, [5-14C] glutamate from the substrate on a cation-exchange column. The enzyme activity was determined in human and rat tissues and in cultured cells. The enzyme activity in fibroblasts from a patient was deficient and that of the parents ranged between 25 and 60% of the control values. In addition we have found the enzyme expressed in native and cultured chorionic villi indicating a potential detection of the disease during the first trimester of pregnancy.

Animals↗

Combined intrauterine and ovarian pregnancy: a case report.

A case of combined intrauterine and ovarian pregnancy diagnosed by postoperative microscopic observations is reported in this paper. The patient was a 23-year-old, Japanese nulligravid female. On the 32 day after a previous D & C when normal chorionic tissues of very early gestation were obtained, she complained of severe lower abdominal pain. Immediate laparotomy revealed hemorrhaging from a hematoma-like region on the surface of the left ovary, and partial resection of the left ovary was performed. The resected ovary was composed of an intact corpus luteum and another thin corpus luteum around a hematoma-like region containing chorionic villi, confirming this case to be an ovarian pregnancy. Histological findings of chorionic villi of the ovary indicated that ovarian pregnancy took place during the same menstrual period as intrauterine pregnancy, and not after the prior D & C. From these observations, this case was diagnosed as a combined intrauterine and ovarian pregnancy.

Abortion, Induced↗

[Placenta membranacea. Review of the literature, a case report].

Placenta membranacea or placenta diffusa is a rare abnormality in which all or most of fetal membranes remain covered by chorionic villi, because the chorion has failed to differenciate into chorion laeve and chorion frondosum. This condition is associated with recurrent antepartum bleeding, abortion in the second trimester of the pregnancy, preterm delivery, fetal death, intra-uterine growth retardation, post partum haemorrhage and placental retention. In this paper, we report our first case of placenta membranacea. A 30-year-old black woman, gravida 3, para 1, was admitted at 23 weeks of gestation for vaginal bleeding. She was placed on complete bed rest. Ultrasonographic examination showed a placenta covering the anterior and posterior uterine walls and the internal cervical os. At 28 weeks and 34 weeks of gestation, ultrasound examination showed the same findings: total placenta previa covering the entire uterine wall and presenting many lacuna. At 38 weeks, she underwent a cesarean section. The placenta adhered firmly to the myometrium. Because the attempts to remove the placenta was unsuccessful, it was performed a total hysterectomy. The total blood loss was 7000 ml. Anatomo-pathologic examination of the placenta led do the diagnosis of placenta membranea, total previa and increta. In the literature, 35 cases of placenta membranacea have been reported; of these, there are ten cases associated with total hysterectomy.

Adult↗

Prenatal diagnosis of heterozygosis in a pregnancy at risk for Wolman's disease at the 8th week of gestation.

Wolman's disease is a rare autosomal recessive disease due to lysosomal acid lipase complete deficiency (McKusick 27.800). Prenatal diagnosis is based on safe chorionic villus sampling procedures. We test acid lipase activity in cultured chorionic villus cells, selected from a biopsy performed during the 8th week of pregnancy. We now report the first prenatal diagnosis of heterozygosity for Wolman's disease during the first trimester of pregnancy. Reduced acid lipase activity was shown in the chorionic villi cells using a natural substrate (Cholesterol 14C oleate). The diagnosis was confirmed by the demonstration of reduced acid lipase activity in cultured amniotic cells and in the newborn lymphocytes. Early prenatal diagnosis in pregnancies at risk for lysosomal storage diseases is possible when enzyme activity levels in chorionic villi are similar to those in cultured amniotic cells and in infant cells.

Chorionic Villi↗

[Morphology of the materno-fetal metabolic barrier in the human placenta].

On chorionic villi of normal human placentas obtained from different aged females morphological studies were made with a view to collecting new data on the molecular structure and material composition of the materno-fetal metabolism barrier. The basement membrane of the chorionic epithelium is characterized by a network of fine collagen filaments arranged parallel to the plane of the membrane and having diameters less than 200 A. Lying between the filament proteins are lipid molecules in the form of bimolecular lamellae, which with their longitudinal axes are oriented approximately vertical to the plane of the membrane and whose thickness is about 40 A. There are many bimolecular lipid layers. In addition, noncollagenic proteins and uronic-acid-free polysaccharides were also found in the epithelial basement membranes. The submicroscopic organization of the endothelial basement membrane of fetal capillaries is different from that of the epithelial basement membrane of chorionic villi. Whereas lipid components disposed vertically to the plane of the membrane and parallelly oriented protein filaments are also present, collagen seems to be nonexistent as is evident from polarization-optical results. Running parallel to the surface of villi and in the apical sections of the plasmodium are protein filaments which are arranged in the form of a network and probably have certain mechanical functions. The structure of the outer membrane is similar to that of the basement membranes because of the presence there in of oriented lipid inclusions. In the region of microvilli and in the outer zone of the plasmoditrophoblast of young placenta there has been found N-acetyl neuraminic acid. The so-called "placental fibrinoid" in the intervillous space is exclusively composed of fibrin. There are no additions of collagen to be found. Therefore, it appears unjustified to use the term "fibrinoid". Glycosaminoglycanes are present in the stroma of villi, and they are oriented in the direction of disposition of collagenous fibers. Their content in the stroma of villi decreases with the progress of gravidity. They are also involved in displacental material transport, although the degree of involvement decreases with the progress of gravidity. Functionally, they show what has been called a "molecular screening effect". The lipid-protein system of the epithelial basement membrane-together with the endothelial basement membrane of fetal vessels in the second half of gravidity-is the principal barrier to the passive passage there-through of substances.

Basement Membrane↗

Selection of maternal human immunodeficiency virus type 1 variants in human placenta. European Network for In Utero Transmission of HIV-1.

To determine the mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses the placenta into the fetal blood, 12 matched samples of serial maternal blood, term placentas, and infant blood obtained from a cohort of pregnant women in Cameroon identified as predominantly infected by subtype A viruses were studied. HIV-1 env sequences were detected by polymerase chain reaction (PCR) in both chorionic villi and enriched trophoblastic cells of all 12 placentas but at variable rates of detection. Heteroduplex mobility assay analysis showed the presence of multiple HIV-1 env quasispecies in sequential maternal peripheral blood mononuclear cell samples, but only a small number of env variants were found in chorionic villi and enriched trophoblastic cells. These data indicate that HIV-1 env sequences are always present in term placentas of seropositive women, contrasting with the low frequency at which infection is diagnosed by PCR in neonates with tat, gag, and env primers. Maternal HIV-1 variants appear to undergo a strong negative selection by different cell populations within the placental villi.

Base Sequence↗

[Analysis of chromosomal aberrations in the chorionic cells of induced abortions as a method for estimating the level of spontaneous mutagenesis].

Chromosomes were morphologically studied in the chorionic fibroblasts of induced abortions. Chorionic villi biopsy specimens taken during 103 abortions at gestational weeks 6-12 served as a material for this investigation. They were taken from women with pregnancies interrupted due to that there were social indications. Metaphase and prometaphase chromosomal specimens were obtained by the test modified by V. Baranov 4-5 hours after chorionic villi biopsy, without preliminarily tissue cultivation. A cytogenetic analysis revealed an abnormal karyotype in 2.91%. The frequency of chromosomal aberrations may serve as a control for prospective studies of spontaneous mutagenesis in a region and the chorion of induced abortion may be regarded as a test unit of mutagenic and embryotoxic effects on the fetus.

Abortion, Induced↗

DNA methylation represses FMR-1 transcription in fragile X syndrome.

Fragile X syndrome is the most frequent form of inherited mental retardation and segregates as an X-linked dominant with reduced penetrance. Recently, we have identified the FMR-1 gene at the fragile X locus. Two molecular differences of the FMR-1 gene have been found in fragile X patients: a size increase of an FMR-1 exon containing a CGG repeat and abnormal methylation of a CpG island 250 bp proximal to this repeat. Penetrant fragile X males who exhibit these changes typically show repression of FMR-1 transcription and the presumptive absence of FMR-1 protein is believed to contribute to the fragile X phenotype. It is unclear, however, if either or both molecular differences in FMR-1 gene is responsible for transcriptional silencing. We report here the prenatal diagnosis of a male fetus with fragile X syndrome by utilizing these molecular differences and show that while the expanded CGG-repeat mutation is observed in both the chorionic villi and fetus, the methylation of the CpG island is limited to the fetal DNA (as assessed by BssHII digestion). We further demonstrate that FMR-1 gene expression is repressed in the fetal tissue, as is characteristic of penetrant males, while the undermethylated chorionic villi expressed FMR-1. Since the genetic background of the tissues studied is identical, including the fragile X chromosome, these data indicate that the abnormal methylation of the FMR-1 CpG-island is responsible for the absence of FMR-1 transcription and suggests that the methylation may be acquired early in embryogenesis.

Base Sequence↗

Cytotrophoblast cells: a barrier to maternofetal transmission of passive immunity.

The human fetus receives passive immunity via the chorioallantoic placenta in the form of maternal immunoglobulin G (IgG) class antibodies. This provides protection against pathogens at a time when the fetus is immunologically naive. We localized endogenous human IgG using confocal laser scanning fluorescence microscopy and immunoelectron microscopy of frozen sections of chorionic villi from early and late gestation. With confocal microscopy we also investigated the distribution of a receptor for IgG (Fc gamma RIII; CD16) that is typically expressed on the surface of human leukocytes. Endogenous IgG was present in the syncytiotrophoblast that surrounds chorionic villi but underlying cytotrophoblast cells were devoid of endogenous antibody. Fc gamma RIII immunoreactivity was confined to the syncytiotrophoblast and was also absent from cytotrophoblast cells. We propose that cytotrophoblast cells present a barrier to the transmission of maternally derived IgG across the human placenta. This accounts for the paradox that there are low levels of transport in the first trimester when the syncytiotrophoblast is known to express receptors for IgG. Cytotrophoblast cells form an almost complete epithelial layer underlying the syncytiotrophoblast at this stage of gestation, but this becomes discontinuous as the placenta matures, thus removing the cellular impediment to IgG transmission.

Cesarean Section↗

The influence of needle and syringe size on chorionic villus sampling of term placentae: a randomised trial.

OBJECTIVE: To determine the effect of needle and syringe size on the amount of tissue obtained at chorionic villus sampling METHODS: Two needle sizes, 18 and 20 gauge, and two syringe sizes 5 mL and 20 mL, were used to assess samples from term post-partum placentae. Each of the four combinations was tested by 25 aspirations. The placentae were divided into 100 grid spaces and each grid space was randomly allocated to a needle/syringe combination. The resulting samples were cleaned to separate the chorionic villi (CV), centrifuged and then weighed. RESULTS: Significantly more tissue was obtained with an 18-g needle compared with a smaller 20-g needle (median weight difference 1.5 mg, 95% CI 0.8-2.3 mg). More tissue was also obtained with the larger 20-mL syringe though the impact of the syringe size was less than that of the needle size (median difference 0.8 mg, 95% CI 0-1.6). CONCLUSION: A larger syringe and needle size yields a larger quantity of chorionic villi from the post-partum term placenta.

Chorionic Villi Sampling↗

Trisomy/tetrasomy 21 mosaicism in CVS: interpretation of cytogenetic discrepancies between placental and fetal chromosome complements.

Trisomy/tetrasomy 21 mosaicism was found in chorionic villi (semidirect preparation) obtained from a 40 year old pregnant woman. Since both cell lines were abnormal, the couple elected for pregnancy termination. Placenta and fetal tissue samples were obtained for cytogenetic study. Long term cultured villi showed a non-mosaic trisomy 21 karyotype, while other tissues showed either a normal karyotype or normal/trisomy21 mosaicism. These discrepancies could be explained by a modified "bottle neck" embryogenic model with a trisomic zygote and a non-disjunction event taking place in one of the first divisions. Our case emphasises the need for confirmatory studies in other tissues when mosaicism is encountered in chorionic villi, even if all cell lines are abnormal.

Adult↗

Modulation of PAPP-A expression by PPARgamma in human first trimester trophoblast.

Pregnancy-associated plasma protein-A (PAPP-A) is a metzincin metalloproteinase that cleaves the insulin-like growth factor (IGF)-dependent binding protein-4 and increases in maternal serum during pregnancy. In human placenta PAPP-A is expressed both in villous cytotrophoblasts (VCT) that cover the chorionic villi and in extravillous cytotrophoblasts (EVCT) of the anchoring villi. Due to the key role of PPARgamma in human trophoblast differentiation such as syncytiotrophoblast formation and EVCT invasion, we studied the effect of PPARgamma activation on PAPP-A expression using our in vitro model of EVCT and VCT primary cultures isolated from the same first trimester chorionic villi. First, we demonstrated that invasive EVCT expressed and secreted 10 times more PAPP-A than VCT did. Then, we showed that activation of PPARgamma inhibited PAPP-A gene expression and secretion in EVCT, whereas it had no effect in VCT. Since we have previously shown that PPARgamma agonist inhibits EVCT invasion in vitro, we suggest that PPARgamma-mediated inhibition of PAPP-A might decrease the amount of bioactive IGFII, a factor known to promote trophoblast invasion.

Chorionic Villi↗