Ly49 knockdown in mice results in aberrant uterine crypt formation and impaired blastocyst implantation.

Genetic knockdown (KD) of the mouse Ly49 receptor family is reported to result in infertility despite the presence of zona-enclosed blastocysts in the uterus. Ly49 receptors regulate leukocyte functions particularly Natural Killer (NK) cell functions and are analogous to human killer immunoglobulin-like receptors (KIRs). Histological analyses of gd3.5-4.5 B6.Ly49(KD) uteri identified hatched but retarded blastocysts with pyknotic nuclei, aberrant endometrial crypt formation and impaired uterine lumen closure accompanied by a lack of primary decidualization These data support peri-implantation roles for leukocytes expressing the Ly49 receptor repertoire and may give insight into KIR-based regulation of human infertility.

Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration.

It has been shown that in non-invasive prenatal testing (NIPT) there is a small chance of a false-positive or false-negative result. This is partly due to the fact that the fetal cell-free DNA present in maternal plasma is derived from the cytotrophoblast of chorionic villi (CV), which is not always representative for the fetal karyotype due to chromosomal mosaicism. Therefore, a positive NIPT result should always be confirmed with invasive testing, preferably amniocentesis, in order to investigate the fetal karyotype. However, since this invasive test can only be safely performed after 15.5 weeks of gestation while NIPT can be done from the 10(th) week of gestation, this potentially means an unacceptable long waiting time for the prospective parents to receive a definitive result. Based on our experience with cytogenetic investigations in CV and the literature, we determined whether CV sampling may be appropriate for confirmation of an abnormal NIPT result.

Placental mesenchymal dysplasia, a case of intrauterine sudden death.

Placental mesenchymal dysplasia (PMD) is a rare condition presenting with enlarged, multicystic placenta like molar changes. Although PMD usually features a normal fetus and the pregnancy often extends into the third trimester, PMD is clinically significant lesion with high rates of FGR, IUFD, and is associated with Beckwith-Wiedemann syndrome (BWS). We report a 30-year old woman at her first pregnancy with intrauterine sudden death at 31 weeks of gestation. The vesicular lesion in her uterus was detected at 10 weeks on ultrasound. The fetus was normal size without any anomaly on ultrasound and normal trophoblastic vascularization by Doppler study during the pregnancy. As the pregnancy advanced, the vesicular lesion decreased in size and no fetal abnormalities were detected. At 28 weeks of gestation an ultrasound detected dilated periumbilical chorionic vessels. We didn't detect severe FGR or abnormal trophoblastic vascularization. At 31 weeks of gestation an intrauterine sudden death of a normal-sized fetus without any anomaly occurred. The placenta was enlarged, and microscopic morphology confirmed a diagnosis of PMD. The chorionic vessels were cirsoid, dilated and tortuous. We determined the rupture of expanded periumbilical chorionic vessels led to fetal death.

Mosaicos cromosómicos en vellosidad corial / Chromosomal mosaicism in chorionic villi

Introducción. El estudio de vellosidades coriales comprende realizar 2 cultivos celulares que pueden no tener resultados coincidentes. Estas discrepancias pueden ser debidas a mosaicos citogenéticos de origen in vivo o in vitro. En este trabajo nos planteamos analizar los cariotipos en mosaicos, ligado con los rendimientos de los cultivos celulares y los resultados citogenéticos. Material y métodos. Se han analizado 2.360 muestras prenatales y 510 de vellosidades de abortos. Con las muestras prenatales se efectúan rutinariamente 2 cultivos celulares, cultivo corto y cultivo largo, y para los abortos además se han estudiado muestras de restos fetales. Resultados. El porcentaje de muestras con resultado citogenético para el grupo prenatal fue del 99,9% y para el grupo de abortos del 87,1%. El porcentaje de anomalías cromosómicas en el grupo prenatal fue del 10,6% siendo las aneuploidías comunes (trisomías 13, 18, y 21) las más frecuentes, y para el grupo de abortos fue del 55,1% siendo las aneuploidías no-comunes las más frecuentes. El porcentaje de cariotipos en mosaico para el grupo prenatal fue del 3,1% y para el grupo de abortos del 6,8%. El mosaico confinado a la placenta tipo ii fue el más frecuente. Conclusiones. Para el estudio de los mosaicos en vellosidades coriales la mejor estrategia es realizar los 2 cultivos paralelos en muestras prenatales y los 3 cultivos en muestras de abortos. Teniendo en cuenta el riesgo que asume la pareja ante una prueba invasiva, es nuestro deber dar el resultado citogenético más completo posible(AU)

Introduction. The study of chorionic villus samples comprises performing two cell cultures that may not have matching results. These discrepancies may be due to cytogenetic mosaics of in vivo or in vitro origin. This study included analysing the karyotypes in mosaics, associated with the cell culture and cytogenetic results. Material and methods. Prospective study based on the analysis of 2,360 chorionic villus samples and 510 spontaneous abortion samples. Two cultures were routinely performed on the prenatal samples (short and long), as well as on the abortion samples. Results. The success rate was 99.9% in the prenatal group, and 87.1% in the abortion group. The percentage of chromosomal anomalies in the prenatal group was 10.6%, with the common aneuploidies (trisomy 13, 18, and 21) being the most frequent. In the abortions group there 55.1% anomalies, with uncommon aneuploidy the most frequent. The percentage of mosaicism in the prenatal group was 3.1%, and it was 6.8% in the abortion group. The confined placental mosaicism type ii was the most frequent. Conclusions. For the study of the mosaicism in chorionic villi samples the best strategy is to perform 2 prenatal samples cultures in parallel, and 3 abortion samples cultures. Given the risk to the mother and child using this invasive test, it is our duty to give the most comprehensive cytogenetic results achievable(AU)

Alteraciones morfológicas de las vellosidades placentarias asociadas a malformaciones fetales múltiples del sistema esquelético / Morphological changes in placental villi associated with multiple malformations of the skeletal system

Describir y cuantificar alteraciones morfológicas en vellosidades placentarias de embarazadas cuyo feto desarrolló malformaciones esqueléticas múltiples. MÉTODOS: se analizaron cuatro placentas de abortos terapéuticos a las 13, 16, 20 y 38 semanas de gestación. Estas se compararon con placentas normales a la misma edad de gestación de abortos electivos por indicación médico legal. Tinción de hematoxilinaeosina se aplicó a 10 láminas de 5 regiones de cada placenta utilizando un protocolo con 4 variables cuantitativas: madurez, cambios fibrinoides, edema y fibrosis estromal y una variable cualitativa: trombosis. Los resultados cuantitativos se analizaron utilizando el análisis de varianza (ANAVAR) según arreglo completamente aleatorizado y el test de Tukey. Para la variable cualitativa se aplicó la prueba de tendencia para datos correlacionados. Se empleó el software statistix 8.0 y SAS 9.0 para Windows. RESULTADOS: existen diferencias significativas (p<0,05) entre las placentas asociadas a malformaciones múltiples del sistema esquelético y las placentas control en relación a las variables cuantitativas. No se encontraron diferencias significativas (p>0,05) en relación a la variable cualitativa. CONCLUSIONES: la población de vellosidades placentarias asociadas a malformaciones múltiples del sistema esquelético presentó un alto porcentaje de alteraciones indicando que la barrera placentaria está dañada afectando el intercambio de gases, nutrientes y metabolitos durante el desarrollo del feto...

To describe and quantify morphological changes in placental villi in pregnancies with multiple fetal malformations of the skeletal system. METHODS: four placentas from fetuses of gestational ages 13, 16, 20 and 38 weeks, aborted for therapeutic reasons were examined. Normal placentas of the same gestational age, from cases where legal elective abortion had been recommended on medical grounds, were taken as the control. The hematoxilineosin stain was applied to ten slides in five regions of each placenta using a protocol with four quantitative variables: maturity of villi, fibrinoid changes, edema and stromal fibrosis and one qualitative variable: thrombosis. The quantitative results were analyzed using ANOVA in a randomized manner and the Tukey test was applied; for the qualitative variable the trend test for correlated data was used. The software used was Statistix 8.0 and SAS 9.0 for Windows. RESULTS: there were significant differences (p<0.05) between the placentas associated with multiple malformations of the skeletal system and control placentas in terms of the quantitative variables. No significant differences were found (p>0.05) in relation to the qualitative variable. CONCLUSIONS: the population of placental villi associated with multiple malformations of the skeletal system exhibited a high percentage of changes which is an indication that the placenta is damaged, thereby affecting the exchange of gases, nutrients and metabolites during the development of the fetus...

Abnormal villous morphology associated with triple trisomy of paternal origin.

The vast majority of trisomies in spontaneous abortions (SAB) are single and of maternal origin, most frequently due to meiosis I errors. Triple trisomies are exceedingly rare (approximately 0.05% of spontaneous abortions), most often of maternal origin, and associated with increased maternal age. Some trisomic SAB specimens can exhibit abnormal villous morphology simulating a partial hydatidiform mole, a distinct form of hydatidiform mole characterized by diandric triploidy. A SAB specimen from a 27-year-old woman, G1P0 at 8 weeks gestational age, was reviewed in consultation to address the finding of morphological features suggestive of a partial hydatidiform mole but DNA ploidy analysis yielding a diploid result. The villi were irregularly shaped and hydropic but lacked trophoblastic hyperplasia; p57 expression was retained. Since fully developed features of a partial hydatidiform mole were lacking, additional analysis was performed. Molecular genotyping and single nucleotide polymorphism array analysis demonstrated biparental diploidy with trisomy of chromosomes 7, 13, and 20, all of paternal origin. The three trisomies may have originated from paternal meiosis II errors, or from mitotic nondisjunction. We believe this to be the first report of triple trisomy in a SAB confirmed to be of paternal origin.

Cambios degenerativos coriónicos asociados a malformaciones fetales del tubo neural durante el tercer trimestre del embarazo / Chorionic degenerative changes associated to fetal neural tube malformations during the third trimester of pregnancy

Evaluar las características de las vellosidades placentarias, sus vasos y espacio intervelloso. Estudio descriptivo, observacional, cualitativo-cuantitativo, retrospectivo, con muestreo no probabilístico de 6 placentas asociadas con malformación del tubo neural, analizadas mediante miscrocopia de luz comparadas en igual número de placentas no asociadas a malformación del tubo neural que sirvieron como controles. Los resultados se analizaron con la prueba de tendencia para datos correlacionados de respuesta dicotómica. Laboratorio de Microscopia Electrónica, CIADANA, Facultad de Ciencias de la Salud, Maracay. Se observaron nódulos sincitiales, cambios fibrinoides, necrosis trofoblástica, edema, fibrosis estromal, trombosis, inflamación de la pared del vaso, un número de vasos de 4 a 6 por sección de vellosidad, calcificación intraluminal, daño de la pared del vaso, trombosis intervellosa y presencia mínima de células inflamatorias en las vellosidades observadas. Hubo diferencias significativas con respecto a edema y necrosis trofoblástica entre ambos grupos. En el grupo de estudio una mayor proporción de edema y necrosis trofoblástica provocarían la eliminación de vellosidades cuyas placentas están con deficienca placentaria indicando que aquellos cambios o agentes causales de la malformación fetal también estarían provocando anomalías en el desarrollo placentario.

La vellosidad placentaria en caso de anemia drepanocítica / The placentary villi to case of drepanocytic anemia

Describir los efectos de la hemoglobinopatía SS en la organización histoarquitectónica de las últimas ramificaciones periféricas del árbol velloso maduro. Se tomaron imágenes de micrografías de luz y electrónica de barrido con las alteraciones sufridas. Centro de Investigación y Análisis Docente Asistencial del Núcleo Aragua. facultad de Ciencias de la Salud. Laboratorio de Microscopia Electrónica. Maracay. Estado Aragua. Deposición de fibrinoide intravelloso incrementado se observó en las diferentes vellosidades infiltrado por células X trofoblástica. Es notorio el incremento de nódulos sincitiales. Hay necrosis del trofoblasto. El estroma contiene vasos dilatados y congestionados con uno o tres eritrocitos nucleados. Se identificó hemorragia estronal, necrosis endotelial, fibrosis y desorganización estromal por edema hidrópico, calcificación, infartos vellosidades intermedias maduras con deficiencia de vellosidad terminal. Los resultados indican cambios degenerativos a nivel de la barrera placentaria que pronostican retardo del crecimiento intrauterino similar al encontrado con mala perfusión de la vellosidad placentaria de origen fetal o materno.

Topically applied minoxidil may cause fetal malformation: a case report.

BACKGROUND: Minoxidil is a K(+) channel opener able to cause relaxation of vascular smooth muscles and modify cell growth and cell fate or migration. It is now widely used for its hair growth promoting effects. When locally applied, it is absorbed through the skin and may have systemic pharmacological effects. CASE: A 28-year-old white pregnant woman daily applied minoxidil 2% to her scalp because of hair loss. At the 22nd gestational week, after a routine ultrasound test showing significant brain, heart, and vascular malformations of the fetus, pregnancy was interrupted. The placenta had numerous ischemic areas and a discrepancy between gestational age and villi maturation. In the villi, capillaries were increased in number, significantly enlarged, and excessively marginalized. The fetus' heart was increased in volume and had a globose shape, the aorta had a distal stenosis. The sigmoid colon was significantly increased in length and a mesentery commune was present. The brain had enlarged ventricles and abundant hemorrhages. Histological examination showed areas of demyelinization with gliosis, signs of excessive and inappropriate angiogenesis, and capillary rearrangement. CONCLUSIONS: Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women.

Intervellositis histiocítica crónica y aborto de repetición / Chronic histiocytic intervillositis and recurrent miscarriage

La intervellositis histiocítica crónica (TVHC) es una infrecuente lesión placentaria, de posible origen inmunológico. Se ha asociado con abortos de repetición y resultados adversos en el embarazo. Se caracteriza por la presencia de un abundante infiltrado inflamatorio en el espacio intervelloso, compuesto principalmente por monocitos y macrófagos. El diagnóstico diferencial incluye varias entidades, y por el momento no pueden descartarse causas infecciosas (AU)

Morphology and DNA content analysis in the evaluation of first trimester placentas for partial hydatidiform mole (PHM).

Partial hydatidiform moles (PHM) have defined villous abnormalities and are usually triploid. Their diagnosis often can be made by morphology alone, without confirmation of ploidy, but considerable interobserver variability exists. Other genetic abnormalities such as trisomy can result in placentas with abnormal villous morphology (AVM) similar to that seen in PHMs, leading to diagnostic confusion. Twenty-three cases originally diagnosed as either PHM or AVM were independently reviewed by 3 pathologists. The consensus diagnosis was PHM in 14 cases and AVM in 9. Cases with AVM showed insufficient features for an unequivocal diagnosis of PHM. DNA content was determined on paraffin-embedded tissue by fluorescence in situ hybridization (fsSH) using a chromosome 1 centromeric probe and by image cytometry (IC). Thirteen of 14 cases (93%) classified as PHM were triploid by both FISH and IC. Seven cases of AVM were diploid by FISH and IC, and 1 was triploid by FISH and IC. One of the 9 cases of AVM was determined to be trisomy 18 by karyotyping. This good correlation of consensus diagnosis with ploidy data was much greater than that obtained based on original diagnoses. Comparative genomic hybridization performed on 6 cases of AVM showed gain of chromosome 21 in 1 case and loss of X in another. PHMs displayed at least 3 of the following histologic features: 2 discrete populations of villi, circumferential mild trophoblastic hyperplasia, trophoblastic inclusions, prominent scalloping of villi, cistern formation. Nontriploid AVMs displayed at most 2 of the diagnostic features of PHM. Placentas with genetic abnormalities other than triploidy can display morphologic changes suggestive of PHM and can be misinterpreted as such by routine light microscopy. Stringent application of morphologic criteria improves the correlation of the diagnosis of PHM with triploidy.

[Morphology and morphometry of placentas showing lethal chromosome aberrations]. / Morphologie et morphométrie des placentas d'aberration chromosomique léthale.

By means of morphological data it is possible to recognize most triploid, many trisomic, and some X monosomic ova. A study by direct smear of the diameter and morphology of the villi and of the relative proportions of other histological structures confirmed the particular characteristics of certain chromosome aberrations.