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[Quantitative investigation of reproduction of condensed chromatin of sex chromosomes during trophoblast cell polyploidization and endoreduplication in the East European field vole Microtus rossiaemeridionalis].

Simultaneous measurement of DNA content in cell nuclei and condensed chromatin bodies formed by heterochromatized regions of sex chromosomes (gonosomal chromatin bodies, GCB) has been performed in two trophoblast cell populations of the East-european field vole Microtus rossiaemeridionalis, namely in the proliferative population of trophoblast cells of the junctional zone of placenta and in the secondary giant trophoblast cells. One or two gonosomal chromatin bodies have been observed in trophoblast cell nuclei of all embryos studied (perhaps both male and female), In the proliferative trophoblast cell population, characterized by low ploidy levels (2c-16c), and in the highly polyploid population of secondary giant trophoblast cells (16c-256c), the total DNA content in GCB increased proportionally to the ploidy level. In separate bodies, the DNA content rose also in direct proportion with the ploidy level seen in the nuclei with both one and two GCBs in the two trophoblast cell populations. A certain increase in percentage of the nuclei with 2-3 GCBs was shown in the nuclei of the junctional zone of placenta; this may be accounted for by genome multiplication via uncompleted mitoses. In the secondary giant trophoblast cell nuclei (16c-256c), the number of GCBs did not exceed 2, and the share of nuclei with two GCBs did not increase, thus suggesting the polytene nature of sex chromosome in these cells. At different poloidy levels, the ratio of DNA content in the nucleus to the total DNA content in GCB did not change significantly giving evidence of a regular replication of sex chromosomes in each cycle of genome reproduction. In all classes of ploidy, the mean total DNA content in trophoblast cell nuclei with single heterochromatic body was less than in the nuclei with two and more GCBs. This may indicate that a single GCB in many cases does not derive from the fusion of two GCBs. To put it another way, in the nuclei with one GCB and in those with two or more GCBs, different chromosome regions may undergo heterochromatization. The regularities observed here are, most probably, associated with the peculiarities in the structure of X- and Y-chromosomes in a range of species of Microtus (M. agrestis, M. rossiaemeridionalis, M. transcaspicus). As a result, gonosomal chromatin bodies may include large blocks of both constitutive heterochromatin of X- and Y-chromosomes (in male and female embryos) and inactivated euchromatin of "lyonized" X-chromosome in female embryos. Therefore the presence of two or more GCBs in trophoblast cells of M. rossiaemeridionalis may be accounted for by both polyploidy and functional state of the nucleus, in which gonosomal constitutive heterochromatin and inactivated euchromatin form two large chromocenters rather than one. The differences in DNA content in GCBs in the nuclei with one and two GCBs seem to be an indirect indication that the two chromocenters may be formed by two different gonosomes, with the extent of their heterochromatization being higher than that in the nuclei with one GCB. GCBs in the trophoblast cells of M. rossiaemeridionalis are observed not only at the early developmental stages, as it was observed in rat at the first half of pregnancy (Zybina and Mosjan, 1967), but also at the later stages, up to the 17th day of gestation. At these stages, the nuclei with non-classical polytene chromosomes rearrange to those with a great number of endochromosomes, probably because of disintegration of chromosomes into oligotene fibrils. However, it does not seem unlikely that this process may involve heterochromatized gonosomal bodies, since only one or two large GCBs can be seen in the nuclei as before. The presence of prominent blocks of constitutive heterochromatin seems to favor a closer association of sister chromatids in polytene chromosomes, which prevents their dissociation into endochromosomes with the result that polyteny of sex chromosomes in the field vole trophoblast is probably retained during a longer period of embryonic development.

Animals↗

Delayed-interval delivery: extended series from a single maternal-fetal medicine practice.

OBJECTIVE: Our purpose was to review the extended experience of a single maternal-fetal medicine practice with delayed-interval delivery. STUDY DESIGN: We completed a retrospective review of our maternal-fetal medicine practice database from January 1991 through March 1999. Patients were derived from both primary and consultative practices. All patients were managed with tocolysis, antibiotics, and cerclage after delivery of the first fetus(es). Retained siblings were investigated by amniocentesis to exclude intra-amniotic infection. RESULTS: Twenty-four consecutive patients had attempted delayed-interval delivery. Exclusion criteria for delayed-interval delivery included monochorionicity, abruptio placentae, severe preeclampsia, and the need for hysterotomy. The mean latency interval was 36 days, with a range of 3 to 123 days. Additionally, patients with previous cerclage(s) had significantly shorter mean latency intervals than patients without previous cerclage(s). Patients with long latency intervals (> or =49 days) had earlier births of the first fetus. CONCLUSION: Selected multichorionic pregnancies may benefit from delayed-interval delivery. Patients with previous cervical cerclage(s) during the index pregnancy are less likely to achieve significant latency intervals. Even modest intervals between births of siblings at critical gestational ages can improve neonatal survival and decrease neonatal morbidity.

Cervix Uteri↗

Prior cesarean and the risk for placenta previa on second-trimester ultrasonography.

OBJECTIVE: To determine whether the increased risk of placenta previa at delivery in patients with a prior cesarean results from an increased risk of abnormal implantation or a lower likelihood of resolution. METHODS: A hospital-based, case-control study was performed. Cases were defined as singleton pregnancies with a placenta previa on second-trimester ultrasonography. Controls, chosen randomly from patients without a placenta previa on second-trimester ultrasonography, were matched 3:1 with cases. Odds ratios (OR) were calculated, controlling for other independent risk factors for previa: age, parity, race, and smoking. RESULTS: There were 88 cases identified and 264 controls. Twenty cases (22.7%) and 35 controls (13.3%) had a history of prior cesarean delivery. Previous cesarean delivery was an independent risk factor for previa on second-trimester ultrasonography (OR 1.92, 95% confidence interval [CI] 1.04-3.55), as was the number of cesareans (OR 1.62, 95% CI 1.12-2.34). However, neither retained their significance after adjusting for other known risk factors for previa (OR 1.50, 95% CI 0.77-2.92, and OR 1.40, 95% CI 0.93-2.10, respectively). At delivery, a history of cesarean was associated with a 3-fold increased risk of previa. CONCLUSION: A previous cesarean delivery did not increase the odds for detecting a placenta previa on second-trimester ultrasonography. At delivery, a previous cesarean was associated with a previa, suggesting a lower likelihood of resolution.

Adult↗

[The immunohistochemical detection in the human placenta of proteins related to the blood coagulation system].

Distribution in mature human placenta of plasminogen, pregnancy-associated inhibitors of proteases (pregnancy-associated protein A (PAPP-A) and alpha 2--pregnancy-associated glycoprotein, and also of not associated with pregnancy alpha 2-macroglobulin and alpha 1-antitrypsin was examined. Primary monospecific antibodies and secondary antibodies labeled with colloid gold were used. Plasminogen was detected in the fetal and maternal blood, and also on the surface of some placental villi (as thin positively stained rims). Pregnancy-associated protease inhibitors were detected in the syncytium of the villi of all histological types and also in the fetal and maternal blood. Staining for alpha 2-macroglobulin was most intensive. This antigen was detected in the maternal and fetal blood and on the surface of the villi. alpha 2-antitrypsin was detected in the fetal and maternal blood. It has been shown that both free plasminogen and its inhibitors are retained on the surface of the placental villi.

Blood Coagulation↗

Centromeric DNA break in a 10;16 reciprocal translocation associated with trisomy 16 confined placental mosaicism and maternal uniparental disomy for chromosome 16.

Stable centromeric breakage in non-acrocentric chromosomes and balanced reciprocal translocation mosaicism are both rare events. We studied a family in which the mother had mosaicism for a balanced reciprocal translocation between chromosomes 10 and 16 which was associated with a break in chromosome 16 centromere alpha-satellite DNA ¿146,XX,t(10;16)(q11.2;q11.1) [29]/46,XX[25]¿. The derivative chromosome 16 contained only a very small amount of 16 alpha-satellite DNA while the derivative 10 contained all of the 10 alpha-satellite DNA as well as a large amount of the 16 alpha-satellite DNA. The same translocation was present in all cells in her son who was found prenatally to have trisomy 16 mosaicism ¿46,XY,t(10;16) (q11.2;q11.1)mat[22]/47,idem,+16[4]¿. Trisomy 16 cells were subsequently determined to be confined to the placenta. DNA polymorphism analyses in the family demonstrated maternal uniparental disomy for chromosome 16 in the diploid child. The child, at age 7 months, had minor facial anomalies similar to a previously reported case of maternal uniparental disomy for chromosome 16. In addition to illustrating several rare events, this family further demonstrated that substantial deletion of the centromeric alpha-satellite DNA does not impair centromere function and both mitotic and meiotic stability are retained in such cases.

Adult↗

[Morphologic features of immune interrelationships in the feto-placental system in development of a large fetus and in retardation of intrauterine fetal development].

Indirect criteria of the value of the immune placenta barrier in case of a large foetus are distinguished: relatively small volume of the fibrinoid substance, moderate synthesis by the syncytial epithelium of glucosaminoproteoglycans (GAPG), slight lymphoplasma cell infiltrates with a marked suppressor influence, the lack of antigens HLA = Dr on the trophoblast and formation of the adequate interrelation ship between the immune dependent placental structure and the thymus of the large foetus this allowing to retain the foetus up to 38-40 weeks or even more. In case of delay in the intrauterine foetus development there is a sharp increase of the fibrinoid substance, focal enhancement of GAPG production by the syncytial cells, decrease of the suppressor activity and the appearance in some cases in the trophoblast of antigens to HLA=Dr this being probably the manifestation of a premature exhaustion of compensatory-adaptive reactions in the placenta.

Chorionic Villi Sampling↗

Growth factors that stimulate human granulocyte-macrophage colony formation produced by the cell line CM-S.

CM-S is an autonomous cell line of human hemopoietic precursor cells inducible to monocyte-macrophage differentiation in response to appropriate inducing agents. CM-S cells produce factors that stimulate their own growth and proliferation, and are also capable of stimulating clonal proliferation of human, but not mouse, monocytic and granulocytic bone marrow progenitor cells in viscous medium. Preliminary purification steps have demonstrated at least two species, one of which (MW 30,000-50,000) retains both these activities, while the other (MW less than or equal to 10,000) apparently retains only the autostimulatory activity. CM-S cells could thus be a useful source for the purification of human colony stimulating factors (CSFs). CM-S cells also respond to factors present in human placenta conditioned medium, known to contain human CSF. This suggests that CM-S cells could provide a homogeneous target cell population for testing CSFs from other human sources.

Animals↗

Single cause for initiation of labor and toxemia: a hypothesis.

A hypothesis is presented that states that the decline in oxygen tension (PO2) in the intervillous space causes both toxemia (preeclampsia-eclampsia) and the initiation of labor. The trophoblast is identified as the monitor of the fetal PO2 and as the source of substances that are released into the maternal circulation stimulating the myometrium, the heart, the vascular smooth muscle, and, perhaps, the brain. In the presence of normal trophoblast the release takes place only when the PO2 in the intervillous space decreases to a level at which the fetus should be expelled from the uterus to avoid intrapartum hypoxia. Near term, the myometrium is the most responsive site to the released substances, and stimulation of the heart and systemic vasculature is observed only infrequently. With release of these substances, intrapartum toxemia results. Toxemia before onset of labor is created by hypoxia of the trophoblast in the presence of a nonresponsive myometrium to materials released. A small placenta, compression of the intervillous space by villous edema, and avulsion of spiral arterioles are the main causes of the premature decline of intervillous space PO2, leading to toxemia. Postpartum toxemia is produced by the retained (extraplacental) trophoblast, perhaps facilitated by the rapid clearance of progesterone.

Animals↗

Outcome of cesarean section in twin pregnancy.

In an 8-year period (January 1978 to December, 1985), the 17,379 deliveries at the University of Benin Teaching Hospital (UBTH) consisted of 2089 cesarean sections (12.0%), 56 of which were associated with twin pregnancy. The main indications for cesarean section on the twin pregnancies were antepartum hemorrhage (placenta previa), malpresentation, cervical dystocia and previous cesarean section. The maternal mortality rate was 2% for all twin mothers delivered by cesarean section. There was no statistical difference in perinatal mortality rates (PMR) for all twin deliveries, vaginal twin deliveries and deliveries by cesareans section which were 111,113 and 100 per 1000 births, respectively. In the case of a retained second twin, however, recorded PMR was significantly higher (133 per 1000 births). Consideration of more liberal recourse to cesarean section in all cases of twins may reduce these unacceptably high perinatal death rates in twin pregnancy.

Age Factors↗

Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells.

The presence within bone marrow of a population of mesenchymal stem cells (MSCs) able to differentiate into a number of different mesenchymal tissues, including bone and cartilage, was first suggested by Friedenstein nearly 40 years ago. Since then MSCs have been demonstrated in a variety of fetal and adult tissues, including bone marrow, fetal blood and liver, cord blood, amniotic fluid and, in some circumstances, in adult peripheral blood. MSCs from all of these sources can be extensively expanded in vitro and when cultured under specific permissive conditions retain their ability to differentiate into multiple lineages including bone, cartilage, fat, muscle, nerve, glial and stromal cells. There has been great interest in these cells both because of their value as a model for studying the molecular basis of differentiation and because of their therapeutic potential for tissue repair and immune modulation. However, MSCs are a rare population in these tissues. Here we tried to identify cells with MSC-like potency in human placenta. We isolated adherent cells from trypsin-digested term placentas and examined these cells for morphology, surface markers, and differentiation potential and found that they expressed several stem cell markers. They also showed endothelial and neurogenic differentiation potentials under appropriate conditions. We suggest that placenta-derived cells have multilineage differentiation potential similar to MSCs in terms of morphology and cell-surface antigen expression. The placenta may prove to be a useful source of MSCs.

Adult↗

[Correlated interrelationships between the concentrations of chorionic gonadotropin, progesterone and estriol in normal pregnancy].

A study was made of 151 healthy pregnant women at periods of from 4 to 41 weeks of pregnancy. There was revealed no correlation between the level of excretion of the CG and estriol, and also of the CG and pregnandiol from the 7th to the 41st weeks of pregnancy; consequently CG played no role in the regulation of steroidogenesis in the placenta. Between the levels of CH and progesterone in the blood there existed a significant positive association from the 4th to the 7th week of pregnancy; this correlation disappeared from the 8th week. Consequently, the CG retained its steroidogenic action on the corpus luteum of pregnancy. The activity of the corpus luteum in respect to progesterone production decreased considerably as soon as the 7th week of pregnancy.

Chorionic Gonadotropin↗

Glycosylation of human trophoblast integrins is stage and cell-type specific.

Cytotrophoblasts are the specialized epithelial cells of the placenta. During the first trimester, a subpopulation of chorionic villus cytotrophoblasts differentiates along an invasive pathway and penetrates the maternal endometrium, decidua and spiral arterioles. Cytotrophoblast invasiveness declines rapidly during the second half of gestation. Isolated cytotrophoblasts of different gestational ages retain this differential invasiveness in culture. To determine whether the properties of integrin receptors for extracellular matrix molecules differ between invasive and non-invasive cytotrophoblasts, detergent extracts of isolated cytotrophoblasts of different gestational ages, and of first-trimester villous fibroblasts, were immunoprecipitated with subunit-specific anti-beta 1 integrin antibodies. Striking alterations in electrophoretic mobility were observed in beta 1 integrins from first-trimester cytotrophoblasts, as compared with those from term cytotrophoblasts or first-trimester villous fibroblasts, suggesting a cell-type-specific, temporally regulated alteration in glycosylation. Treatment of total first-trimester cytotrophoblast beta 1 integrins or the isolated alpha 5/beta 1 fibronectin receptor with endo-beta-galactosidase restored electrophoretic mobility to control levels, suggesting the presence of polylactosamine-bearing oligosaccharides. Further analysis by enzyme digestion and lectin-affinity chromatography suggested that they consisted of at least three antennae and short, sialylated lactosamine units. These oligosaccharides did not affect the affinity of the first-trimester cytotrophoblast fibronectin receptor for fibronectin. However, this receptor bound more strongly to wheat germ agglutinin than control fibronectin receptor and resisted elution by high concentrations of sugar hapten, requiring ionic detergent for removal. These results suggested that the altered glycosylation affected the conformation of the fibronectin receptor.

Amino Acid Sequence↗

Cellular changes in the peripartum bovine fetal placenta related to placental separation.

Binucleate giant cells (BNC) decline in number and viability peripartum if the placenta is subsequently released normally. This suggests an involvement of BNC destruction in fetal membrane separation in the cow. Dexamethasone induction of parturition may result in fetal membrane retention through a stabilization of the BNC (possibly the BNC plasma membranes). Prostaglandin F2a treatment in vitro induced a loss of BNC when these were obtained from cows which subsequently retained the fetal membranes for a longer than normal interval. Overall, our results indicate an involvement of BNC loss and breakdown in placental separation and a possible involvement of prostaglandins and glucocorticoids in modulating this process.

Animals↗

Differentiation of trophoblast lineage is associated with DNA methylation and demethylation.

Our previous study has shown that the placenta and kidney had different genomic methylation patterns regarding CpG island loci detected by restriction landmark genomic scanning (RLGS). To investigate whether differentiation involves changes in DNA methylation, we analyzed the rat Rcho-1 cell line, which retains trophoblast cell features and differentiates from stem cells into trophoblast giant cells in vitro. By RLGS, a total of 1,232 spots were identified in the Rcho-1 stem and differentiated giant cells. Four spots (0.3%) were detected only in giant cells, implying that the loci were originally methylated, but became demethylated during differentiation. Another four spots (0.3%) were detected only in stem cells, implying that these loci, originally unmethylated, became methylated during differentiation. DNAs from three loci that became methylated during differentiation were cloned and sequenced. All showed high homologies with expressed sequence tags (ESTs) or with genomic DNA of other species, suggesting that these loci are biologically important. Thus, the eight differentially methylated loci should be good tools to study epigenetic modification specific to differentiation of trophoblast giant cells.

Animals↗

A pregnancy after planned partial endometrial resection.

A 28-week pregnancy is reported after a planned partial endometrial resection in an infertile patient. The fetus died 32 hours after birth because of prematurity consequent to premature membrane rupture and premature labour. A partial placenta accreta was dealt with at Caesarean section. Complete endometrial resection may not be required to cure menorrhagia. It may be possible to control menorrhagia by targeting specific areas of endometrium associated with menorrhagia. Fertility may be retained by leaving the fundal and peritubal endometrium. The increased risks of pregnancy complications following endometrial resection suggest that more information is required to design endometrial resection so as to both cure menorrhagia and to sustain successful pregnancy.

Adult↗

Polarizable placental particles: a case study and brief review of the literature.

Two otherwise healthy pregnant women presented with intrauterine fetal demise and underwent unremarkable induction of labor. Histopathologic examination of both placentas revealed polarizable foreign material with minimal associated tissue reaction in the membranes and adjacent maternal decidua. No overt foreign body giant cell reaction or inflammation was seen, suggesting recent introduction of the material. Further review of the histories showed that both women had undergone cervical ripening with laminaria. These are strips of collagenous seaweed placed in a closed cervix, where they absorb moisture and swell, dilating the cervix and hastening the onset of labor. Microscopic examination and polarization of known laminaria fragments identified this substance as the likely source of the polarizable material within the placental membranes. Laminaria fragments should be distinguished from other polarizable materials such as talc, suture, and retained foreign bodies on the basis of their histologic appearance and the acute nature of the accompanying tissue reaction.

Adult↗

Placental cathepsin M is alternatively spliced and exclusively expressed in the spongiotrophoblast layer.

Cathepsin M and cathepsin-3 are cysteine peptidases expressed exclusively in the murine placenta. Their expression increases continuously from 11.5 dpc until the end of gestation. The cathepsin M gene consists of 8 exons and 7 introns covering 6 kb of genomic DNA on mouse chromosome 13. Multiple variants of CTSM were identified which display alternative splicing of exon 2 or exon 7. Alternative splicing of exon 2 does not affect the translated region of CTSM whereas aberrant splicing of exon 7 will results in enzymatically inactive versions of CTSM which still might retain inhibitory activity towards cysteine peptidases. Besides two defined major transcription start sites the putative promoter region comprises of a TATA-box and a relatively low (41%) G+C content reflecting its highly specific spatial and temporal expression pattern. Similar features are found within the promoter region of CTS3 which is highly homologous to CTSM. Both cathepsin M and -3 expression are confined to the spongiotrophoblast layer of the mouse placenta an expression pattern which is unique among cysteine peptidases located within the cluster of cathepsin J-like peptidases on mouse chromosome 13.

Alternative Splicing↗