Invasión trofoblástica en el embarazo normal (II): Placentación profunda(Trophoblastic invasion in normal pregnancy (II): Deep placentation)Eduardo Reyna-Villasmil1, Carlos Briceño Pérez2, Joel Santos-Bolívar1.1 Servicio de Obstetricia y Ginecología. Hospital Central “Dr. Urquinaona”. Maracaibo. Estado Zulia. 2 Departamento de Obstetricia y Ginecología. Unidad Docente Hospital Chiquinquirá. Universidad del Zulia. Maracaibo. Estado ZuliaRecibido: 13 de Febrero de 2014Aceptado: 15 de Mayo de 2014Publicación online: 15 de Junio de 2014 [ARTÍCULO DE REVISIÓN]ResumenLa placentación profunda en el embarazo en humanos es realizada por la invasión profunda del lecho placentario por el trofoblasto extra-velloso, involucrando la decidua y el miometrio interno (zona de unión del miometrio). Se produce la invasión intersticial del estroma y la invasión trofoblástica endovascular de las arterias espirales. La invasión trofoblástica endovascular profunda dentro de los segmentos del miometrio de las arterias espirales es importante para la función adecuada de la placenta. La remodelación vascular de la decidua, que incluye inflamación y desorganización del músculo liso vascular, ocurre durante el periodo de aumento de la oxigenación placentaria. Este paso de remodelación temprana puede acompañar el incremento progresivo del aumento del flujo sanguíneo materno a la placenta en desarrollo. Los pasos posteriores de remodelación asociados al trofoblasto potencian y estabilizan la ampliación de los vasos, mientras que el músculo liso vascular y la lámina elástica son reemplazadas por una matriz fibrinoide rodeado por trofoblastoPalabras claveInvasión del trofoblasto; Arterias espirales; Lecho placentario; Remodelación vascular.AbstractDeep placentation in human pregnancy is done by deep invasion of the placental bed by the extravillous trophoblast, involving the decidua and the inner (junctional zone) myometrium. Interstitial invasion of the stroma and endovascular trophoblast invasion of the spiral arteries both occur. Deep endovascular trophoblast invasion into the myometrial segments of spiral arteries is important for proper placental functioning. Decidua-associated vascular remodeling, which includes swelling and disorganization of the vascular smooth muscle, occurs during a period of rising placental oxygen. This early remodeling step may accommodate the progressively increasing maternal blood flow to the developing placenta. The subsequent trophoblast-associated remodeling step enhances and stabilizes the widening of the vessels, whereas the vascular smooth muscle and elastic lamina are replaced by a fibrinoid matrix with embedded trophoblast.KeywordsTrophoblast invasion, spiral arteries, placental bed, vascular remodeling.Introducción La placentación es el proceso en el cual las células trofoblásticas darán origen a la placenta que en humanos es única, autónoma y transitoria. La placenta hemocorial representa la forma más primordial de la circulación materna y fetal, en el cual la optimización del flujo de sangre materna es parcialmente afectada por la actividad invasora del trofoblasto. En los humanos, la invasión del trofoblasto extravelloso alcanza una mayor profundidad que en la mayoría de los mamíferos. Esta invasión está asociada con una extensa remodelación de los segmentos miometriales y deciduales de las arterias espirales. Aparte de esto se observa la implantación intersticial del blastocito con un alto grado de erosión decidual. La invasión de la pared uterina comienza con la implantación del blastocito, la cual es intersticial en vez de superficial y resulta en la formación de la decidua capsularis. Este aspecto se comparte con otros primates. La implantación en los humanos, como en cobayos y chimpancés, es tipo intersticial, en la que el blastocisto se “enclava” o “empotra” dentro del tejido del estroma sub-epitelial. El proceso de implantación se inicia con la aparición del trofoblasto sincicial en la pared del blastocito (1). Una vez que se completa la implantación intersticial, el blastocito es rodeado completamente por el sincicio “primitivo” (2). Al mismo tiempo, las células sinciciales son consideradas como el trofoblasto invasivo primordial en los humanos (3).El objetivo de la presente revisión una visión general de la implantación normal y de los diferentes mecanismos implicados en la placentación profunda y la remodelación vascular del lecho placentarioGonadotropina coriónica humana en la implantación, formación de vellosidades y placentaciónComo se ha descrito en varias publicaciones (4, 5), La gonadotropina coriónica humana (hCG) es producida principalmente durante el embarazo por las células del sinciciotrofoblasto mutilinuclear fusionadas (las células que transfieren los nutrientes de la placenta) y la hCG hiperglicosilada (hCG-H) se produce en las células del citotrofoblasto extravelloso (el componente invasor de la placenta). Durante el embarazo, la hCG tiene numerosas funciones. Como se publicó en 1920, la hCG promueve la producción de progesterona en las células del cuerpo lúteo. Esta acción endocrina es limitada, sin embargo, al momento de la implantación y en las tres semanas posteriores (3-6 semanas de embarazo) (6). La progesterona producida en este periodo es necesaria para mantener la decidua y evitar el sangrado menstrual. También promueve la angiogénesis de la vasculatura uterina materna para que las arterias espirales uterinas alcancen su momento óptimo para la placentación. La hCG suprime el sistema inmune de rechazo materno de los tejidos placentarios y fetales e inhibe las contracciones miometriales hasta el término del embarazo (7, 8). Con el crecimiento del feto, la hCG promueve el crecimiento del útero, modifica los la musculatura lisa miometrial y prepara los tejidos deciduales y miometriales para la recepción de las células trofoblasticas (9-11). También promueve la diferenciación de las células citotrofoblasticas mononucleares a células multinucleadas del sinciciotrofoblasto, las cuales son las células funcionales de la barrera de circulación materno-fetal (6-8, 12). La hCG también tiene funciones durante el embarazo en el crecimiento y diferenciación de los órganos fetales.La hCG-H producida por las células del citotrofoblasto promueve el crecimiento y la invasión al momento durante la invasión y la implantación (13). Como se ha demostrado, la hCG-H bloquea la apoptosis en las células del citotrofoblasto, además de promover el crecimiento (14). Las metaloproteinasas (MMPs) son las que conducen la invasión durante la implantación del embarazo (15, 16). Aunque la hCG-H promueve el crecimiento de las células citotrofoblasticas durante el embarazo, la hCG también promueve la diferenciación de estas células en las vellosidades flotantes (el sitio activo de del intercambio de nutrientes materno-fetal). La combinación de hCG-H y hCG puede llevar al crecimiento y diferenciación del citotrofoblasto y, en conjunto, al crecimiento de las vellosidades trofoblasticas.Decidualización, erosión decidual y la forma de la membrana basal28Cerca del momento de la implantación, comienza espontáneamente la decidualización en el endometrio humano. El proceso involucra distensión de las células del tejido conectivo y cambios en la matriz extracelular. También incluye cambios de remodelación temprana en las arterias espirales deciduales (crecimiento y vacuolización endotelial acompañado con desorganización del músculo liso vascular). Al mismo tiempo el contaje de leucocitos en el endometrio se altera en forma drástica, principalmente por infiltración de macrófagos y células natural killer uterinas (uNK), las cuales tienen un papel en la remodelación vascular temprana (17).La complejidad de la función de decidualización es poco comprendida, y puede no solo estar limitada a un papel nutricional, inmune o endocrino. El proceso de transformación decidual temprana puede contribuir al tipo de implantación intersticial, lo cual puede depender de la capacidad de invasión y de decidualización del tejido endometrial para encapsular el embrión, actuando al mismo tiempo como un “biosensor” para reconocer (y eliminar) los embriones defectuosos (18). La decidualización optima puede necesitar del “acondicionamiento” adecuado del endometrio, lo cual puede requerir de una sucesión de varios ciclos menstruales (19).En el embarazo temprano, una capa decidual compacta enfrenta la cubierta citotrofoblástica. En los monos, esta permanece intacta por largo tiempo del embarazo (20). Para los humanos, la cubierta se desintegra mientras que la decidua es progresivamente invadida por el trofoblasto intersticial. Esta invasión comienza en el centro del lecho placentario y progresivamente se disemina hacia la periferia en forma de anillo (21, 22). Entre las células que migran, se pueden observar bandas de trofoblasto bi, tri y multinucleadas, indicando fragmentación de las láminas sinciciales desplazadas durante la formación de la cubierta citotrofoblástica o fusión gradual del trofoblasto mononuclear invasor (3). Esas células gigantes multinucleares pueden alcanzar un gran tamaño dentro de la decidua y el miometrio interno. Se ha sugerido que, debido a su gran tamaño, la penetración en la superficie miometrial interna puede ser difícil (23, 24). 29En contraste con la placenta de los monos Rhesus, en los humanos el límite entre la membrana basal placentaria y la decidua es extremadamente irregular. Más aún, generalmente la mayoría de las arterias espirales en el lecho placentario humano muestran una orientación casi paralela a la membrana basal. Sobre la superficie de esos vasos, se pueden formar aperturas adicionales en el espacio intervelloso, las cuales posiblemente son responsables de los cambios necróticos en las porciones de la decidua que contienen los segmentos de las arterias espirales más dístales que han sido cortadas por las nuevas aperturas (23, 24).La ubicación de las aperturas laterales de las arterias espirales es probablemente el resultado del crecimiento expansivo lateral del disco placentario, causando estiramiento y aplanamiento de las estructuras endometriales maternas subyacentes, como lo indican los acúmulos de glándulas endometriales en las áreas laterales del lecho placentario. Las aperturas adicionales son probablemente creadas por la acción del trofoblasto intersticial invasor. Se puede pensar que durante el crecimiento lateral progresivo de la placenta, las placas necróticas del tejido decidual, aún unidas a las vellosidades de anclaje, son empujadas hacia el centro y protruyen dentro del tejido placentario. De esta forma, se pueden formar los septos placentarios, ya que poseen un centro de tejido decidual (25, 26). La erosión decidual y formación de septos placentarios son menos obvias en la placenta de los primates debido a la baja actividad invasora del trofoblasto intersticial y a restricción de la expansión placentaria. Este escenario para la formación de los septos es apoyado por la observación que la mayoría de las aperturas de las arterias espirales en el espacio intervelloso ocurren en la base de los septos protuidos (25). El incremento de la erosión decidual puede explicar el cambio de las aperturas arteriales de intralobular a interlobular en los humanos. La más prominente acción erosiva de la placenta sobre la decidua subyacente puede ser causada por una invasión intensa del trofoblasto, lo cual podría ser apoyado por una más extensa decidualización (27). Este concepto contradice la mera función de restricción de la invasión previamente descrito en la placenta de los roedores (28). En los humanos, existe evidencia, que indica que la decidualización puede iniciar y estimular la invasión del trofoblasto (29). No se considera que el punto final de esta decidualización es restringido por el endometrio mismo, sino por alteraciones de la decidua que se extienden hacia la zona de unión del miometrio (ZUM) (30). Estas modificaciones incluyen cambios en la matriz extracelular y un “debilitamiento” del músculo liso miometrial, al igual que una remodelación temprana de los segmentos miometriales de las arterias espirales. Esta transformación asociada a la decidualización del miometrio interno podría suministrar un estímulo adicional a la invasión trofoblástica profunda más allá de la unión deciduo-miometrial.Invasión trofoblástica intersticial profundaA partir de las 8 semanas, un mayor número de trofoblasto extravelloso mononuclear aparece dentro del lecho placentario humano, pero no fuera de esta región (21, 22). Aunque las técnicas inmunohistoquímicas no estaban disponibles al momento de los estudios iniciales, los hallazgos en estas células (marcada basofilía y forma oval) permiten la fácil diferenciación del tejido miometrial que lo rodea. Al estudiar la ZUM en conjunto con la decidua que lo recubre, es obvia la continuidad de las células basofílicas en el miometrio con el trofobolasto mononuclear que invade la decidua basal. La cuantificación de las células invasoras en diferentes sectores del lecho placentario indica que la profundidad de la invasión miometrial comienza en el centro del lecho placentario, como en la decidua, pero progresivamente se expande a regiones más laterales. El patrón de invasión se refleja en la sección completa del lecho placentario, indicando una diseminación en forma de anillo hacia la periferia (21, 22). La invasión es intruisiva donde las células trofoblásticas penetran a través del epitelio luminal, alcanzando la membrana basal y extendiéndose posteriormente hasta el estroma donde el sinciciotrofoblasto invade rápidamente hasta llegar a las arterias espirales. Este tipo de invasión además de presentarse en humanos ocurre en cobaya y hurón.La posición del trofoblasto intersticial en relación con las arterias espirales cambia de la decidua hacia el miometrio. En la decidua, el trofoblasto intersticial tiende a concentrase alrededor de los vasos sanguíneos; sin embargo, en la ZUM, se vuelven más dispersos (31). Las células mononucleares forman grupos y se fusionan en células gigantes multinucleadas en la decidua y el miometrio, y su persistencia en este último compartimiento sugiere que han perdido su capacidad invasora. El origen trofoblástico de las células mononucleares invasoras en el miometrio se ha confirmado en estudios posteriores, aplicando técnicas de inmunohistoquímica (23). El progreso de la unión y fusión del trofoblasto mononuclear puede ser confirmado por la sucesiva aparición y desaparición de las moléculas de adhesión entre las células citotrofoblásticas reunidas (32).La función exacta de este trofoblasto intersticial en la ZUM es desconocida. Se ha sugerido un posible papel local en el tejido uterino (3), mientras que otros investigadores (33) han presentado evidencia de una función endocrina, de acuerdo a la localización histoquímica de las enzimas convertidoras de esteroides. Se ha propuesto otra posible función de estudios de la remodelación de las arterias espirales miometriales de la decidua temprana, demostrando una correlación entre el grado de desorganización de las células del músculo liso vascular y la densidad del trofoblasto intersticial. El mecanismo exacto de esta remodelación temprana no está claro, pero los efectos líticos de las enzimas que degradan la matriz secretadas por el trofoblasto sobre los vasos es probablemente el paso inicial en la desorganizaciónRemodelación de las arterias espirales de la decidua antes de la invasión trofoblástica intersticial profundaEl concepto emergente que la decidua actúa como iniciador y estimulo de la invasión del trofoblasto es también aplicable a las arterias espirales. Además de los cambios del estroma endometrial, la decidualización involucra “remodelación asociada a la decidualización” de los segmentos de las arterias espirales endometriales, la cual consiste en inflamación y vacuolización endotelial, desorganización del músculo liso vascular e inflamación de las células del músculo liso (34). En el endometrio decidualizado durante el primer trimestre del embarazo, estos cambios vasculares tempranos parecen ser iniciados por los macrófagos y uNK infiltrantes, a través de la secreción de factores de crecimiento angiogenico (35), y también por la capacidad de producir apoptosis en una proporción de células endoteliales y del músculo liso vascular (17). Esta drástica desorganización produce reducción de la actividad vasomotora, lo cual puede contribuir al incremento del flujo sanguíneo materno a la placenta, aún antes de la aparición de la invasión trofoblástica endovascular. Se ha propuesto que la función de la decidua es dar nutrición, protegerlo de las respuestas inmunológicas maternas y regula la invasión del trofoblasto dentro del útero.30La remodelación asociada a la decidualización se extiende a la ZUM. En los primeros estudios del lecho placentario se han descrito la presencia de edema perivascular, desorganización e inflamación de las células del músculo liso vascular y adelgazamiento de la lámina elástica (figura 1) (33). Las tecnologías de imágenes han confirmado los cambios en la integridad vascular del miometrio interno, comenzando a los 7 días luego de la ovulación (36). Esto suministra apoyo adicional para considerar a la ZUM como un compartimiento separado de la pared uterina (37). Aún se desconoce cuán lejos las células infiltrantes (principalmente macrófagos, debido a que los uNK están ausentes en el miometrio) pueden actuar en este compartimiento como un posible agente iniciador en esta remodelación temprana, como lo hacen en el endometrio (38). Ya se ha indicado que la desintegración e inflamación de las células del músculo liso en los segmentos miometriales son intensificadas por la presencia del trofoblasto intersticial. Se ha demostrado que las células invasoras contienen factores de crecimiento angiogénico (39), parece que ellas sustituyen la actividad de las células uNK que están restringidas al miometrioInvasión trofoblástica endovascular profunda31Después de la invasión endovascular del estroma decidual y miometrial interno, ocurre una segunda invasión endovascular en las arterias espirales del lecho placentario humano (40). Debido a la secuencia de tiempo, se ha propuesto que el trofoblasto endovascular es únicamente trofoblasto intersticial que penetra en la pared de las arterias espirales desde el exterior de la capa adventicia (41). Sin embargo, se ha enfatizado que el trofoblasto intraluminal puede ser identificado como originario de la cubierta citotrofoblástica, indicando un comienzo endovascular diferente (42). Por otra parte, la posibilidad que algo del trofoblasto intersticial pueda invadir las arterias espirales no puede ser totalmente negada. Las diferencias de las densidades perivasculares o el trofoblasto intersticial entre la decidua y el miometrio, sin embargo, pueden ser relevantes. En la decidua, se puede observar un acercamiento perivascular más explícito del trofoblasto vascular que indica la posibilidad de una migración transmural; sin embargo, la dispersión progresiva en el estroma miometrial, el incremento de la distancia de las arterias, parece excluir la contribución intersticial principal al trofoblasto endovascular a un nivel más profundo (31).Figura 1. Arteria espiral miometrial a las 15 semanas. Se observa: 1a, remodelación vascular temprana con inflamación de las células del músculo liso vascular (flechas) y 1b, ausencia de trofoblasto y una lámina elástica fina.Si se acepta la migración intersticial endovascular de las arterias espirales, se esperaría que esta pudiera ser inhibida por la fusión prematura del trofoblasto intersticial perivascular a las células gigantes. Lo que se ha considerado como una explicación para la ausencia de trofoblasto endovascular (e intramural) en las células espirales miometriales en las preeclámpticas, fue apoyado por las observaciones de la cercana asociación de las células gigantes (43). El concepto subyacente fue que, por la fusión de las células gigantes, el trofoblasto intersticial pierde su capacidad invasora y por lo tanto es incapaz de penetrar la pared de los vasos, volviéndose endovascular y migrando más profundamente en las arterias espirales miometriales. Este escenario ha sido negado por un estudio posterior, el cual reveló una alteración más que una aceleración de la fusión del trofoblasto intersticial en el lecho placentario de las preeclámpticas (32).Aún persiste la discusión sobre si la progresión de la invasión endovascular de la decidua al miometrio es un proceso continuo o si ocurre en dos oleadas (decidual y miometrial, respectivamente) con una pausa temporal entre ellas. El concepto de las dos oleadas se originó de estudios de muestras de histerectomías a edades conocidas con la placenta in situ. Tales muestras pueden ser apropiadamente orientadas durante el procesamiento del tejido permitiendo una estimación confiable de la profundidad de la invasión (43), difícil de lograr en las biopsias. La edad gestacional más temprana en la cual se ha logrado determinar el llenado endovascular completo de las arterias espirales deciduales con la presencia de trofoblasto en el centro del lecho placentario es de 10 semanas, mientras que la observación más temprana de migración profunda más allá de la capa miometrial superficial fue hecha después de las 14.Basado en las diferencias entre estos dos puntos temporales, se ha estimado que existen por lo menos 4 semanas entre estas dos fases de la migración (31). Se desconoce la naturaleza de los estímulos que pueden iniciar la segunda oleada de migración en el miometrio, motivando preguntas sobre el significado fisiológico de este fenómeno (33). Sin embargo, en algunas especies de monos, el hecho que la invasión endovascular parece estar restringida a las arterias espirales deciduales podría indicar que la unión deciduo-miometrial suministra un punto final “natural” a la invasión. Esto implica que, para extender esta invasión hacia un compartimiento más profundo, se necesitarían algunos otros mecanismos. El hecho que la invasión miometrial profunda en los humanos permita un periodo de crecimiento rápido del contenido de oxígeno placentario (44), sugiere que el crecimiento sostenido del flujo úteroplacentario, el incremento de las concentraciones de oxígeno, o ambos, podrían ser considerados factores contribuyentes. Sistemas in vitro usando trofoblasto que crece en tubos capilares, han demostrado que el flujo activa las células para iniciar la migración, al menos cuando los tubos están recubiertos de endotelio (45). También se ha publicado evidencia in vitro que el oxígeno es necesario para inducir la capacidad invasora del trofoblasto (46). Si se puede confirmar que el aumento del flujo, el aporte de oxígeno, o ambos, pueden actuar como iniciadores para la segunda oleada de invasión, se podrían proponer mecanismos concretos para explicar la alteración de la invasión profunda en complicaciones del embarazo. Es sorprendente que las concentraciones placentarias de oxígeno en el embarazo temprano aumenten en el momento en que ocurre la remodelación asociada a la decidualización de los segmentos miometriales de las arterias espirales. La alteración de la remodelación de estos vasos podría prevenir o retardar este incremento temprano del flujo y aumento del oxígeno y, por lo tanto, inhibir o retrasar la segunda oleada de invasión. El desarrollo se lleva a cabo en un medio de hipoxia relativa y se estima que pueda sea regulada por otros factores de la matriz extracelular y ciertas citoquinas, factores de crecimiento u hormonas (47).Otro hecho, ampliamente controvertido, es que la invasión del trofoblasto en el lecho placentario en humanos tiene un gradiente central a lateral en sus inicios. La invasión de trofoblasto endovascular e intersticial comienza en el centro. La expansión lateral de la invasión y el incremento de diámetro del disco placentario están obviamente relacionados (48). Estos eventos también están asociados con el estiramiento lateral de las arterias espirales con el desarrollo de aperturas secundarias hacia el espacio intervelloso, posiblemente influido por el efecto erosivo del trofoblasto extravelloso sobre la decidua superficial.El periodo de la invasión profunda, que inicia a las 15 semanas, y su subsecuente progresión lateral para incluir arterias espirales adicionales, que ocurre en una tercera parte de los vasos a la semana 18, puede finalmente determinar el funcionamiento óptimo de la placenta (40). En los embarazos normales a término, la mayoría de las arterias espirales son completamente remodeladas, lo cual implica que la mayoría de las arterias laterales es invadida progresivamente en el transcurso del segundo trimestre. El flujo de sangre materna a la placenta alcanza su máxima capacidad sólo hasta la mitad del embarazo.Remodelación profunda de las arterias espirales y sus consecuencias32La formación del trofoblasto endovascular activa la aparición de la “remodelación” de las arterias espirales. Esto en forma típica afecta los depósitos de material fibrinoide amorfo que reemplaza el músculo liso vascular original, junto con una pérdida completa de la lámina elástica (49, 50). Aunque la pérdida de músculo liso vascular no puede ser explicada por observaciones histológicas en las biopsias del lecho placentario, explantes de segmentos de arterias espirales in vitro muestran inducción de la apoptosis tanto en las células endoteliales como musculares lisas después de agregarle trofoblasto (51). No está claro si los procesos apoptoicos y de desintegración coinciden o no con los depósitos de fibrinoide extracelular en las arterias espirales invadidas. La naturaleza exacta de este material fibrinoide es también desconocida, pero aparentemente es producto de la secreción del trofoblasto intramural (52). El fibrinoide similar a la matriz difiere del fibrinoide similar a la fibrina precipitado del tejido placentario y puede tener una función de adhesión celular en el cual las interacciones mediadas por las integrinas pueden estar involucradas (53).La fibronectina, por ejemplo, es constituyente del fibrinoide de la membrana basal y se cree que juega un papel en la adhesión placentaria a la pared uterina (54). También está presente en los depósitos pericelulares alrededor de las células gigantes del lecho placentario, pero está ausente de los depósitos de fibrinoide dentro de las arterias espirales remodeladas (55). En el pasado, se describió una posible función reguladora en la interacción inmune materno-fetal de la sustancia fibrinoide, pero la presunción que el fibrinoide pericelular tiene un papel en el enmascaramiento de la antigenicidad del trofoblasto no ha soportado el paso del tiempo.Es sorprendente que, en el embarazo temprano, la remodelación del trofoblasto no ocurra como un cambio vascular continuo alrededor de la circunferencia arterial completa, sino que ocurre en forma focal, sugiriendo que las condiciones del flujo local pueden afectar el inicio de la incorporación del trofoblasto intramural y los cambios asociados. En embarazos normales, durante el tercer trimestre, en la mayoría de las arterias espirales se observa la remodelación completa de toda la circunferencia de la pared del vaso; pero en condiciones anormales, el inicio de la remodelación puede no ser completa (56).33Las consecuencias funcionales de la remodelación completa son obvias: la desaparición total del músculo liso vascular puede evitar la vasoconstricción, mientras que la remoción de la lámina elástica evitaría el reacomodo del vaso después de la dilatación. Se esperaría que tan drástica remodelación permitiera un flujo sanguíneo úteroplacentario ininterrumpido y un aporte de oxígeno constante a la placenta. Como se mencionó previamente, los resultados de investigaciones en monos Rhesus han demostrado que la sangre materna es llevada al espacio intervelloso por chorros intermitentes que salen de arterias espirales separadas y en momentos diferentes. La fuerza detrás de este fenómeno debe ser generada por las arterias radiales de paredes gruesas y porciones proximales de las arterias espirales, las cuales, en el mono Rhesus, no están completamente remodeladas (27). En los embarazos normales en humanos no está establecido si se observa un patrón de hechos similar, Debido a la más extensa remodelación, se puede considerar que la eyección de sangre materna intermitente en el espacio intervelloso ocurriría de forma similarÁrbol velloso y flujo intervelloso en la placenta de los primatesEl primer paso en el intercambio materno fetal en la placenta en desarrollo es la formación de lagunas llenas de sangre con engrosamiento de la pared sincicial del blastocito implantado. No está claro si el “espacio intervelloso” primordial representa solamente sangre materna extravasada o es derivado de la red de capilares subepiteliales que han perdido su alineamiento. Durante las primeras semanas, estos espacios sanguíneos maternos solo se comunican con las venulas deciduales, pero a las 8 semanas, se desarrollan los canales conectores entre las lagunas y las venas lagunares (57). En ese momento se establece la base anatómica del flujo de sangre “intervelloso”. Entre tanto, láminas de citotrofoblasto mononuclear comienzan a proliferar en el lado fetal de la pared del blastocito implantado. Las columnas citotrofoblásticas resultantes se transforman en una masa sincicial primitiva, formando vellosidades primarias, secundarias y terciarias (después de la formación de los capilares fetales).El citotrofoblasto más distal atraviesa el sincicio en forma lateral y forma una capa de citotrofoblasto extravelloso, separando la placenta de la decidua superficial. En los humanos, esta capa es solo una estructura temporal y comienza a desintegrarse en fases tempranas del embarazo., constituyéndose de esta manera la placentación hemocorial de los humanos en la cual la sangre materna conecta directamente con el trofoblasto o corion, a diferencia de la placentación endotelio-corial en los que los vasos desnudos maternos endoteliales están en contacto con el corion fetal, observada en la mayoría de los carnívoros como zorros, gatos y perros y de la epitelio corial en la que el epitelio uterino y el corion están en contacto sin invadirlo como se ve en vacas, yeguas y ballenas, también se llama placenta adeciduata (52,57). El trofoblasto extravelloso tiene su origen en las células en las puntas de las columnas de las vellosidades de anclaje. La mayoría de las células comienzan inmediatamente a migrar más profundamente en el tejido materno.La circulación fetal se inicia a las 6 semanas tan pronto como la red de capilares se conecta con el corazón fetal. El flujo sanguíneo materno comienza en una fase posterior y se incrementa gradualmente entre las 8-12 semanas (44), mientras que los tapones intravasculares se disuelven y comienza la migración trofoblástica intravascular de las arterias espirales (58). Solo entonces la placenta puede ser considerada plenamente funcional, con la circulación materna y fetal establecida. Se ha propuesto que la invasión trofoblástica intra-arterial comienza en el centro del lecho placentario, mientras que el flujo materno en la placenta comenzaría en las arterias más laterales (59). Por lo tanto, el incremento del estrés oxidativo en estas regiones laterales es responsable de la regresión progresiva del “corion frondoso” a “lámina corial”.Durante el desarrollo placentario posterior, las vellosidades intermedias y terminales aparecen de la vellosidad principal formando un sistema de árbol velloso, cada uno con un tronco y ramas laterales. Por lo tanto, la placenta se subdivide en unidades funcionales, los lóbulos placentarios. En las placentas jóvenes, cada lóbulo parece contener un centro relativamente vacío con un tejido velloso más denso. Originalmente se pensó que en los espacios centrales abiertos se crearían por la fuerza de la sangre materna entrante, accediendo al espacio intervelloso en las regiones interlobulares del piso placentario (60). Sin embargo, en la placenta humana a término la mayoría de las aperturas de las arterias espirales tienden a estar distribuidas en las áreas interlobulares (48). Esto puede ser causado por la más extensa erosión decidual que ocurre en el embarazo humano como resultado de una invasión trofoblástica más intensa y profunda.Existe acuerdo general que, en la mayoría de las placentas, las direcciones del flujo materno y fetal se contrarrestan, promoviendo un sistema de intercambio más eficiente (61). Este concepto puede ser ilustrado por la organización de la placenta en los roedores. El grueso de la sangre materna es llevado por las arterias espirales directamente a la cara fetal de la placenta por los canales maternos transplacentarios; las ramas arteriales umbilicales principales llevan la sangre fetal al lado materno del laberinto (62, 63). El intercambio fisiológico ocurre entre los capilares fetales y los estrechos espacios sanguíneos maternos del laberinto, mientras que el flujo de sangre fetal y materna regresa en direcciones opuestas. Este tipo de flujo requiere de diferentes arreglos anatómicos en la placenta del mono y del humano, con las arterias espirales abiertas libremente en el espacio intervelloso de la membrana basal. Este arreglo posee el problema que la sangre rica en oxígeno permanecería concentrada alrededor de las aperturas de las arterias espirales, no logrando diseminarse hacia la totalidad de la placenta.Los estudios de imágenes realizados en la placenta de monos Rhesus revelaron que la sangre materna deja las arterias espirales en forma vigorosa, dirigida hacia la lámina coriónica (64). Se ha propuesto que el flujo materno a presión también ocurre en la placenta humana. Este sistema de flujo materno en toda la extensión de la placenta requiere un sistema de vellosidades flotantes. Sin embargo, las placentas de los monos tienen “pseudolaberintos” con numerosas conexiones intervellositarias. El mecanismo intervelloso propuesto para la sangre materna por “chorros” de las arterias espirales sería altamente ineficiente. En cambio, el transporte transplacentario de sangre materna en estos animales es guiado a través de los canales maternos (65), los cuales son comparables a las estructuras análogas en el laberinto de la placeta de los roedores.La invasión trofoblástica profunda del lecho placentario humano involucre una vía intersticial y una vía endovascular, esta última progresa en forma regresiva en la decidua y los segmentos de las arterias espirales, respectivamente. La invasión trofoblástica parece estar cercanamente interconectada con el proceso decidualización, que típicamente comienza alrededor del momento de la implantación y afecta tanto el estroma endometrial y la pared de las arterias espirales. 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Reyna-Villasmil E y cols D Correspondence Author: Dr. Eduardo Reyna-Villasmil, Hospital Central “Dr. Urquinaona” Final Av. El Milagro.Maracaibo, Estado Zulia. VENEZUELA.Teléfono: 584162605233. Email: sippenbauch@gmail.comAvances en BiomedicinaPublicación Oficial del Instituto de Inmunología ClínicaMérida-VenezuelaVolumen 4(1), Ene-Abr 2015, p 27-37Copyright: © ULA 2015Depósito Legal: PPI201102ME3935ISSN: 2244-7881/9j/4AAQSkZJRgABAQEAYABgAAD/2wBDAAIBAQEBAQIBAQECAgICAgQDAgICAgUEBAMEBgUGBgYF BgYGBwkIBgcJBwYGCAsICQoKCgoKBggLDAsKDAkKCgr/2wBDAQICAgICAgUDAwUKBwYHCgoKCgoK CgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgr/wAARCAO7AnYDAREA AhEBAxEB/8QAHgAAAgIDAQEBAQAAAAAAAAAABQYEBwIDCAEACQr/xABbEAABAwIEBAQDBQUFBAYH ABMBAgMEBREABhIhBxMxQRQiUWEIMnEVI0KBkRZSobHRCSQzYsEXcuHwJUNVgtLxChg0U5KTlKKD hLImNURFdKMZVGTCw9NjZbP/xAAaAQACAwEBAAAAAAAAAAAAAAACAwABBAUG/8QAOBEAAgICAgIC AQMDBAEDBAEFAAIDEgEiBDIREzFCUhQhIwVBYjNRYXJxJEOBFYKRoTRTkuHwov/aAAwDAQACEQMR AD8AtGi/aWaq8Ir0lTdidCdR3tjvvqp11QuiqZTbzlw9iUdVIeC45CDocujTfcj0vjGr+uWwnkpu VjnrgznDJcpnN2TnJJbatqDd9RSOoNv540rMrasJw1dizuDdUnZlqzUqsZidiFTKQ2y9+/3Cr9Qe mM0rV6j82pZSxM9ZP4Y53pa4demeHloJQhXM8wWP3QOuMqZlj6gJJLH9TjPjhmpvhv8Aa2WXKs1I 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with perinatally acquired HIV: emerging behavioral and health needs forCompu4Sony22015-05-30T03:52:00Z2015-06-01T23:57:00Z2015-06-01T23:57:00Z

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