Uterine transplantation: a systematic review

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

Modelo experimental de endometrite em vacas inoculadas com Escherichia coli inativada por meio de infusão uterina / Endometritis experimental model in cows inoculated with inactivated Escherichia coli by uterine infusion

The aim of this study was to evaluate the endometrial inflammatory response of nine Zebu cows inoculated through uterine infusion with 30 mL of inactivated Escherichia coli suspension (1 x 109 UFC/mL) and nine with 30 mL of sterile phosphate buffered saline. Endometrial biopsies were performed before and after the inoculations during estrus, and ten days later in the diestrus phase. Neutrophilic infiltrates were observed in 88.8% of samples from the E. coli group in estrus phase and demonstrated different degrees of endometrial inflammation. This study characterizes a suitable model for studying endometritis in cattle.(AU)

Emerging role of uterine natural killer cells in establishing pregnancy

Normal pregnancy has been considered as a controlled state of inflammation at an early stage of blastocyst implantation that subsequently develops systemically. Till recent past most popular hypotheses regarding status of immune system in pregnancy were dominated by the Th[1] and Th[2] hypothesis, in which the fetus avoids maternal rejection through a bias towards I-helper [Th[2]] cytokine production. Recent findings have shown that predominant immune interactions in the human deciduas are between the placental trophoblast and maternal uterine natural killer [uNK] cells rather than the I cells. Thus NK cells are emerging as important players in the uterine immune response to invasive forms of placenta, as in cases of hemochorial placenta. In humans there is a lack of evidence for I-cell responses to trophoblast cells; therefore it was thought that uterine NK cells are the key factors by which the maternal immune system recognizes trophoblast cells. In this review we are trying to summarize the role of uNK cells in the maintenance of normal pregnancy in humans

Positional relationship between natural killer cells and distribution of sympathetic nerves in decidualized mouse uterus

Uterine natural killer [uNK] cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their recruitment and activation is incompletely understood. The major subpopulation of uNK cells in humans expresses CD56, the neural cell adhesion molecule [NCAM]-l while their counterpart in mouse expresses asialoGMl, a brain ganglioside. Sympathetic nerves express NCAM-1 which mediates homotypic binding. Sympathetic fibers innervate the me-sometrial vasculature but their relationship to the myometrial and decidual uNK cell recruitment is unknown. The present study aims to explore positional relationship between natural killer cells and distribution of nerves in decidualized mouse uterus. Immunohistochemistry and mRNA expression for the enzyme tyrosine hy-droxylase were used to map sympathetic nerve fibre distribution within C57BL/6 implantation sites and to address a relationship with uNK cells. Tyrosine hydroxylase positive neurons were identified in the mesometrium closely associated with uterine arteries. Staining became gradually vanished as the nerves crossed the myometrium and entered the decidualized uterus. No neuronal stain was associated with the spiral arteries. Periodic Acid Schiff s reactive uNK cells were absent from the mesentery, but abundant in decidua basalis where they are associated with non-innervated vessels. Data suggest that the recruitment of uNK progenitor cells to the uterus is unlikely to be dependent on signaling by the sympathetic nervous system

Impact of diet on the immunological microenvironment of the pregnant uterus and its relationship to allergic disease in the offspring: a review of the recent literature

Medical progress has reduced the mortality from infectious diseases in most countries, but allergic diseases have become more prevalent worldwide over the same period, especially in industrialized countries. This has prompted speculation that modern lifestyles have altered the relationship between heredity and environment so as to promote development of an atopic phenotype when exposure to infection decreases. A healthy uterine microenvironment is known to favor Th2 lymphocyte development. However, some evidence suggests that persistence of the Th2 pattern of immunity directs the developing organism's immune response towards a long-lasting atopic phenotype. Even though the outcome also depends on other factors (such as infection, functional state of the intestinal microflora, and exposure to environmental allergens at times critical to development), it seems that the immune system during the perinatal period is responsive to interventions that are no longer effective in adulthood. We have reviewed the literature accessible through Medline to identify recent advances in the prevention of allergic disease through interventions in the fetal-maternal relationship. Diet seems to have a significant impact on the immunological profile of the pregnant uterus, as well as on the postnatal development of allergic disease in the offspring, as suggested by the effects of probiotic bacteria and by manipulations of the dietary content of polyunsaturated fatty acids and antioxidants. This highlights the need for further studies, in order to define the best intervention methods, the most appropriate time interval and the individuals who will most likely benefit from them.

Progressos médicos reduziram a mortalidade por doenças infecciosas em muitos países, mas doenças alérgicas tornaram-se mais prevalentes no mundo inteiro, no mesmo período, especialmente nos países industrializados, levando alguns a postular que a vida moderna influencia as relações entre hereditariedade e meio ambiente de forma a favorecer o desenvolvimento de atopia quando a exposição a agentes infecciosos diminui. O micro-ambiente fisiológico do útero gravídico favorece o desenvolvimento de linfócitos Th2. Contudo, a evidência sugere que um padrão persistente de imunidade Th2 direciona a resposta imune do organismo em desenvolvimento para um fenótipo atópico duradouro. Embora o resultado dependa de outros fatores, incluindo infecções, o estado funcional da microflora intestinal, e a exposição a alergenos ambientais em momentos críticos do desenvolvimento, o sistema imune no período perinatal permanece suscetível a intervenções que não têm efeito no adulto. Fizemos uma revisão da literatura acessível através da Medline para identificar avanços recentes na prevenção de doenças alérgicas por meio de intervenção na relação materno-fetal. A dieta parece ter um impacto significativo sobre o perfil imunológico do útero gravídico, assim como sobre o desenvolvimento pós-natal de doença alérgica, como sugerido pelos efeitos de bactérias probióticas e pela manipulação do conteúdo de ácidos graxos poli-insaturados e de antioxidantes na dieta. Isso reforça a necessidade de estudos mais amplos para determinar o melhor tipo de intervenção, o momento mais adequado e os indivíduos que mais serão beneficiados.

Immunoregulatory pathways in pregnancy.

Murine pregnancy is characterized by transient thymic atrophy and splenomegally. Several laboratories are investigating the immunoregulatory mechanisms during pregnancy, and the majority of these studies are primarily focused on the immunological changes either in the uterus or the thymus and not much information is available on the immunological changes in the spleen that result in transient splenomegally. An attempt has been made in this review to understand the significance of thymic atrophy, splenomegally and local immune changes in the uterus to understand the overall immunomodulatory mechanisms in pregnant mother. The most significant change which occurs soon after mating is the infiltration of immune cells such as macrophages and gammadelta-T cells into the uterus indicating that the mother's immune system detects the presence of foreign antigens in the reproductive tract. The sensitized cells appear to migrate to the secondary lymphoid organs including the spleen. The microenvironment in the spleen is conducive for the cell-cell contact and generation of immune response. The major changes that occur in the spleen are, the induction of T-cell dependent B-cell response on day-1 post-coitum (P.C.), generation of antibody producing B-cells on day-3 and also proliferation of CD8+ T-cells that peaks on day-3 of pregnancy. The weight of the spleen reaches a peak on day-10 in mice. Thereafter, on day-15 of pregnancy, lymphocyte apoptosis is seen in the spleen indicating the deletion of peripheral sensitized cells. This results in decrease in spleen weight to that of normal non-pregnant mice. The decrease in thymic weight after day-5 pregnancy was associated with the increased apoptosis of cortical thymocytes. This perhaps is due to negative selection of self-reactive thymocytes. Our studies have demonstrated that the pregnancy associated monoclonal antibodies react with antigens of sperm indicating that the mother's immune system recognizes and responds to the constituents of the semen to produce non-precipitating asymmetric auto antibodies (NPAA) or blocking antibodies which have favourable effects on pregnancy. It is postulated that the mother's immune response could be directed to some antigens of sperm along with some conserved antigens such as heat shock proteins (HSP) that are present both in sperm and in the mother. It may be speculated that after the initial priming to some conserved antigens of sperm and due to the presence of similar antigens in the mother, these activated clones are eliminated both in the primary and secondary lymphoid organs to prevent autoimmunity in the mother during pregnancy.

Localización inmunocitoquímica de la serpina CBG-símil en el sistema reproductor de mamíferos hembra / Immunocytochemical localization of the CBG-like in the mammalian female reproductive system

La participación de la globulina que une corticoides (CBG) en el proceso de la inducción de la reacción acrosomal, ha sido claramente demostrada in vitro en espermatozoides humanos. Esta molécula fue aislada primariamente desde fluido folicular y su presencia, detectada inmunológicamente, ha sido demostrada por nosotros en folículos ováricos, epitelio tubular uterino y en endometrio de humanos y bovinos. Estos resultados nos llevaron a ampliar el estudio de la probable presencia de esta molécula en otras especies mamíferas, con la hipótesis de que si está involucrada en mecanismos previos a la fecundación en humanos y bovinos, su presencia podría estar también jugando un rol molulatorio en especies con procesos de interacción gamética básicamente comparables. El objetivo del presente trabajo fue determinar inmunocitoquímicamente la presencia y distribución de la CBG-símil en el sistema reproductor de cerdos, perros, gatos, conejos y ratas, Las muestras fueron obtenidas, en los distintos estadios del ciclo reproductivo, desde piezas quirúrgicas, a excepción de las de cerdo que se obtuvieron desde su matadera local. Muestras de ovario, tuba uterina y útero fueron procesadas para inmunocitoquímica (ICQ) con anticuerpos (Ac) poli y monoclonales anti hCBG que reconocieron antígenos comunes dentro de las distintas especies animales. En todas ellas la ICQ reveló una intensa reacción positiva a nivel de los folículos ováricos, en las células secretoras del epitelio de la mucosa tubárica y en las células epiteliales de las glándulas y de la mucosa endometrial. En general, la inmuno tinción se manifestó muy intensa hacia el periodo ovulatorio y muy escasa en los periodos de niveles esteroidales bajos. Sin embargo, existieron diferencias particulares entre los distintos animales debido, probablemente, a la variación antigénica por la lejanía de la especie con la molécula generadora del Ac. Muy interesante resultó el estudio del animal en el cual se produjo el Ac policlonal, éste confirmó la presencia de la CBG endógena, determinada por una intensa inmunorreactividad en los preparados controles (sin Ac específico), y que por tanto, la única fuente de ellos fue la proveniente de la generación de sus propios Ac. Nuestros resultados nos permiten sugerir que en las especies estudiadas existe CBG-símil, la cual se distribuye en áreas morfológicas del sistema reproductor, similares a las observadas en humanos y en bovinos