Expresión del fenotipo Duffy negativo en mujeres afrodescendientes y su relación con la preeclampsia / Expression of the Duffy negative phenotype in women of African descent and their relation to pre-eclampsia

La preeclampsia (PE) es una complicación del embarazo que trae consigo algunas consecuencias negativas para la madre y el feto: en la madre provoca principalmente hipertensión y proteinuria, mientras que en el feto puede presentarse trombocitopenia, alteración en el desarrollo del sistema nervioso central y circulatorio, y restricción del crecimiento intrauterino, lo cual se considera el factor de riesgo principal de muerte fetal en nacimientos producto de una PE severa. En la preeclampsia se presenta una disfunción endotelial relacionada con placentación anormal, estado de estrés oxidativo y proceso inflamatorio sistémico, que lleva a la activación de neutrófilos y monocitos. Se ha considerado a la interleucina-8 (IL-8) como un posible candidato desencadenante por ser quimioatrayente y activador de leucocitos; en la circulación sanguínea, la IL-8 se une a un receptor de quimiocina multiespecífico de alta afinidad denominado DARC, que es idéntico al antígeno del grupo sanguíneo Duffy. Este receptor regula los niveles plasmáticos de IL-8, uniéndose a esta quimiocina, pero cuando hay una mutación en la región promotora del gen se altera la expresión de DARC, lo que conlleva a que la IL-8 de los factores genéticos involucrados en la activación de los neutrófilos y de los monocitos, y por ende, en la disfunción endotelial presentada durante este síndrome hipertensivo, especialmente en la población afrodescendiente.

Preeclampsia (PE) is a complication of pregnancy that brings some negative consequences for both mother and fetus. It specially causes hypertension and proteinuria in mothers; while in fetuses it causes thrombocytopenia, development alterations of the central nervous and circulatory system; also intrauterine growth restriction may occur. This last factor is regarded as the main risk factor for fetal death in births as a result of severe PE. There is endothelial dysfunction in preeclampsia related to abnormal placentation, state of oxidative stress and systemic inflammatory process that leads to the activation of neutrophils and monocytes. Interleukin-8 (IL-8) is considered as a possible trigger candidate, since this chemokine is a chemoattractant and leukocyte activator. In the bloodstream, interleukin-8 binds to a high affinity multispecific-chemokine receptor called DARC, which is identical to the Duffy blood group antigen. This receptor regulates plasma levels of IL-8 by binding to chemokine. But, when there is a mutation in the gene promoter region, DARC expression is altered, and IL-8 inefficiently binds to receptor. This mutation results in Duffy negative phenotype, which is present in most of African descendants. This literature review is intended to address the role of IL-8 as neutrophil chemo-attractant, the importance of Duffy blood system and the possible association between ethnicity and preeclampsia.

Lipoxinas inducidas por la aspirina: una alternativa para modular los procesos proinflamatorios en la preeclampsia / Aspirin induced lipoxins: alternative to modulate proinflammatory processes in preeclampsia

La preeclampsia es un síndrome hipertensivo que se presenta a partir de la semana 20 de gestación. El objetivo de este trabajo es describir la producción y los mecanismos de acción de las lipoxinas inducidas por la aspirina y proponerlas como una alternativa adecuada para modular los procesos oxidativos característicos de la preeclampsia y los ciclos proinflamatorios que inician con la cascada de activación del factor nuclear-kappa B, y en consecuencia de sus productos. La preeclampsia se caracteriza por la producción de sustancias proinflamatorias, que inducen la activación de células endoteliales, directa o indirectamente, a través de la activación previa de los monocitos, los cuales pueden generar especies reactivas de oxígeno y expresar moléculas de adhesión que median la interacción con el endotelio, contribuyendo a su estado de disfunción, activación e inducción de la cascada de señalización del factor nuclear-kappa B. La aspirina por su parte, induce la producción de lipoxinas que inhiben la activación del factor nuclear-kappa B mediante el bloqueo de la proteína quinasa IkB, necesaria para desencadenar la activación de la vía canónica y no canónica de este factor nuclear.

Preeclampsia is a hypertensive syndrome that occurs after the 20th weeks of gestation. The objective of this review was to describe the mechanisms of production and action of aspirin- triggered lipoxins in order to consider them as a suitable alternative to modulate oxidative processes, which are characteristic of preeclampsia and proinflammatory cycles starting with cascade activation of nuclear factor-kappa B, consequently of their products. Preeclampsia is characterized by the production of proinflammatory substances that induce directly or indirectly endothelial cell activation,, through prior activation of monocytes, which can generate reactive oxygen species and expression of adhesion molecules that mediate interacting with the endothelium, contributing to its dysfunction, activation and induction of signaling cascade nuclear factor-kappa B. Aspirin induces lipoxin, which inhibits the activation of nuclear factor-kappa B by blocking IkB protein kinase, necessary to trigger the activation of canonical and non-canonical pathway of this nuclear factor.

[Early embryo death: does the male factor play a role?]. / Muerte embrionaria temprana: tiene influencia el factor masculino?

OBJECTIVE: To discuss the possible role of the male factor in early embryo death. METHOD: A detailed bibliographic review has been put together to establish which alterations in spermatozoa can be associated with early embryo death. RESULTS: Before the fusion between plasma membranes of the sperm and the oocyte occurs, both germ cells must undergo a maturation process that allows successful fertilization and embryo development. The study of couples with early embryo loss is usually approached from the side of the woman due to the obvious relationship that exists between the female and the developing embryo. However, it is not illogical to suppose that a genetic or epigenetic alteration of the sperm could have important consequences on these losses due to the necessary contribution of the male gamete not only to embryonic but also to placental development. On the other hand, spermatozoa have certain characteristics such as a highly compact DNA, they undergo apoptosis and the seminal plasma contains antioxidants that protect the structural and functional integrity of the germ cell. These factors assure fertilization and embryo development. Nevertheless, epigenetic alterations of the sperm such as altered chromatin packing, mistakes in imprinting, absence or alteration of the centrosome, telomeric shortening and absence of sperm RNA, could affect functions leading to early embryo loss. CONCLUSIONS: Knowledge concerning sperm intervention previous to embryo development will provide the basis for better understanding and for possible diagnosis and treatment of diverse reproductive alterations in men that could impede embryo development.

Muerte embrionaria temprana: ¿tiene influencia el factor masculino? / Early embryo death: does the male factor play a role?

Objetivo: Discutir el efecto que puede tener el factor masculino sobre la muerte embrionaria temprana. Método: Se hace una revisión de literatura de diferentes componentes del espermatozoide que pueden tener algún papel en la muerte embrionaria temprana. Resultados: Antes que ocurra la fusión entre la membrana plasmática del espermatozoide y la del oocito, ambos gametos deben sufrir un proceso de maduración que permita la fecundación y el desarrollo embrionario exitosos. El estudio de las parejas con muerte embrionaria temprana, usualmente se aborda desde el factor femenino por la obvia relación de la mujer con su producto en desarrollo, pero no es ilógico suponer que una alteración genética o epigenética en el espermatozoide, tenga un papel importante en estas pérdidas por su importancia en el desarrollo placentario y embrionario. El espermatozoide posee algunas características como el empaquetamiento del ADN, la apoptosis y los antioxidantes en el plasma seminal, que protegen la integridad estructural y funcional de la célula germinal, permitiendo que el espermatozoide fecunde al oocito y contribuya al desarrollo embrionario. Sin embargo, alteraciones epigenéticas como el remodelamiento de la cromatina y la consecuente perturbación de los eventos relacionados con la impronta genómica podrían ser causas de origen paterno que pueden tener alguna representación en las muertes embrionarias tempranas como también lo son la ausencia o alteración del centrosoma, el acortamiento telomérico y la ausencia de RNA espermático. Conclusiones: El conocimiento de la intervención espermática en el desarrollo embrionario proporcionará bases para el entendimiento y el posible diagnóstico y tratamiento de diversas alteraciones reproductivas masculinas que puedan estar ocasionando fallas en el desarrollo posterior del embrión (AU)

Objective: To discuss the possible role of the male factor in early embryo death. Method: A detailed bibliographic review has been put together to establish which alterations in spermatozoa can be associated with early embryo death. Results: Before the fusion between plasma membranes of the sperm and the oocyte occurs, both germ cells must undergo a maturation process that allows successful fertilization and embryo development. The study of couples with early embryo loss is usually approached from the side of the woman due to the obvious relationship that exists between the female and the developing embryo. However, it is not illogical to suppose that a genetic or epigenetic alteration of the sperm could have important consequences on these losses due to the necessary contribution of the male gamete not only to embryonic but also to placental development. On the other hand, spermatozoa have certain characteristics such as a highly compact DNA, they undergo apoptosis and the seminal plasma contains antioxidants that protect the structural and functional integrity of the germ cell. These factors assure fertilization and embryo development. Nevertheless, epigenetic alterations of the sperm such as altered chromatin packing, mistakes in imprinting, absence or alteration of the centrosome, telomeric shortening and absence of sperm RNA, could affect functions leading to early embryo loss. Conclusions: Knowledge concerning sperm intervention previous to embryo development will provide the basis for better understanding and for possible diagnosis and treatment of diverse reproductive alterations in men that could impede embryo development (AU)

Functional evaluation of sperm in Colombian fertile men.

OBJECTIVE: The aim of the present study was to evaluate in 111 ejaculates from fertile men membrane integrity of spermatozoa before selection and sperm motility, and sperm concentration and chromatin integrity before and after selection of motile spermatozoo. METHODS: We evaluated the membrane integrity (using hypoosmotic swelling test and Eosin-Y) before separation and chromatin integrity (using acridine orange), concentration and motility before and after separation by migration sedimentation technique. All individuals had pregnant wives or had procreated a baby during the last year. RESULTS: The data of sperm membrane integrity by the eosin-Y and hypoosmotic swelling tests did not show significant statistical differences and the correlation between them was low. The percentage of motile sperm (grades a + b) increased from 57% to 87% (p < 0.001), the concentration decreased from 89 to 31 x 10(6) sperm/ mL (p < 0.001) and chromatin integrity increased significantly (p < 0.0001) after separation of semen. CONCLUSIONS: The great variation in the values obtained in the functional test in fertile males requires a re-evaluation of the use of these tests in clinical practice of infertility.

Evaluación funcional del esperma en varones fértiles columbianos / Functional evaluation of sperm in colombian fertile men

OBJETIVO: El fin del presente estudio fue evaluar en 111 eyaculados de individuos fértiles la integridad de la membrana de los espermatozoides antes de la selección, y la movilidad, la concentración, la integridad de la cromatina antes y después de la selección espermática. MÉTODOS: Evaluamos la integridad de la membrana (usando la prueba de hinchazón hipoosmotica y eosina Y) antes de la selección, y la integridad de la cromatina (usando naranja de acridina) concentración y movilidad antes y después de la separación mediante la técnica de migración sedimentación. RESULTADOS: Los datos de la integridad de la membrana espermática mediante la prueba de hinchazón hipoosmótica y eosina Y no mostraron diferencias estadísticamente significativas y la correlación entre estas fue baja. El porcentaje de espermatozoides móviles (grado a + b) se incrementó de 57% a 87% (p < 0.001), la concentración disminuyó de 89 a 31 x 106 espermatozoides/ mL (p < 0.001) y la integridad de la cromatina se incrementó significativamente (p < 0.0001) antes y después de la separación. CONLCUSIONES: la gran variación en los valores obtenidos en las pruebas funcionales en hombres fértiles requiere una re-evaluación del uso de estas pruebas en la práctica clínica de infertilidad

OBJECTIVE: The aim of the present study was to evaluate in 111 ejaculates from fertile men membrane integrity of spermatozoa before selection and sperm motility, and sperm concentration and chromatin integrity before and after selection of motile spermatozoa. METHODS: We evaluated the membrane integrity (using hypoosmotic swelling test and Eosin-Y) before separation and chromatin integrity (using acridine orange), concentration and motility before and after separation by migration sedimentation technique. All individuals had pregnant wives or had procreated a baby during the last year. RESULTS: The data of sperm membrane integrity by the eosin-Y and hypoosmotic swelling tests did not show significant statistical differences and the correlation between them was low. The percentage of motile sperm (grades a + b) increased from 57% to 87% (p < 0.001), the concentration decreased from 89 to 31 x 106 sperm/mL (p < 0.001) and chromatin integrity increased significantly (p < 0.0001) after separation of semen. CONCLUSIONS: The great variation in the values obtained in the functional test in fertile males requires a re-evaluation of the use of these tests in clinical practice of infertility

Complementariedad intergametos: breve revision / Intergamete complementarity: short review

OBJETIVO: El objetivo de esta revisión es reconocer el papel de varias moléculas que están participando en la interacción intergametos durante el inicio de la fertilización y su posible relevancia en el desarrollo de un método contraceptivo. MÉTODO: Se hace una revisión de literatura sobre la interacción intergametos. RESULTADOS: La fertilización es el producto de una serie de procesos ordenados que deben sufrir tanto el espermatozoide como el oocito para interactuar y generar un nuevo ser; para que esta interacción se produzca es necesario que ambas células se encuentren en perfecto estado y que se de un reconocimiento, que es dependiente tanto de los residuos de oligosacáridos presentes en la zona pelúcida del oocito, como de receptores presentes en la membrana plasmática (receptores primarios) y en la membrana acrosomal interna (receptores secundarios) del espermatozoide. CONCLUSIONES: El conocimiento sobre estos procesos originará un mejor entendimiento de los mecanismos moleculares de esta interacción intergametos y podría llevar al desarrollo de herramientas tanto para control de la reproducción como para el estudio de parejas con alteraciones de la fertilidad (AU)

[Intergamete complementarity: short review]. / Complementariedad intergametos: breve revision.

OBJECTIVE: The aim of this review is to recognize the role of molecules involved in intergamete interactions during the process of fertilization and further understanding of the molecular basis of fertilization in humans for the development of new methods for contraception. METHODS: We carried out a bibliographic review on intergamete interactions. RESULTS: Fertilization is the product of a series of ordered steps that must take place both in the sperm and the oocyte for a correct interaction leading to the development of the new individual; this interaction requires that both cells are in perfect state for recognition to occur; this recognition is dependant on terminal oligosaccharide residues present in zona pellucida and their complementary receptors on sperm plasmatic (primary receptors) and inner acrosomal (secondary receptors) membranes. CONCLUSIONS: Knowledge of these processes will provide a better understanding of the molecular mechanisms in intergamete interaction and could lead to the development of tools for controlling reproduction as well as for helping couples presenting alterations of their

Pregnancy outcome in women with antiphospholipid syndrome and alloimmunity: a case report.

CONTEXT: Patients with antiphospholipid syndrome and alloimmunity have poor pregnancy outcomes. Several diagnostic and therapeutic options exist for these disorders, although there is no consensus as to the best treatment. CASE REPORT: We present here the clinical course and treatment of a woman with a history of two miscarriages who joined our program 10 years ago and has been followed up ever since. After antiphospholipid syndrome and alloimmune failure were diagnosed, she was given preconceptional treatment using unfractionated heparin, aspirin, prednisone and lymphocyte immunizations. She delivered two premature babies in the following two pregnancies. At present both children are healthy and are attending school. The fifth pregnancy was unsuccessful, in spite of having undergone a similar but postconceptional therapeutic scheme. We discuss this case focusing on the pathogenic mechanisms and the therapeutic aspects of these disorders.

Pregnancy outcome in women with antiphospholipid syndrome and alloimmunity: a case report

CONTEXTO: Mulheres com síndrome do anticorpo antifosfolípide e aloimunidade têm um mau prognóstico de gravidez. Existem muitas opções para o diagnóstico e o tratamento destas doenças, embora o tratamento mais adequado não esteja estabelecido. RELATO DE CASO: Apresentamos a evolução clínica e o tratamento de uma mulher com antecedentes de dois abortos e que vem sendo acompanhada, há 10 anos, em nosso serviço. Após o diagnóstico da síndrome do anticorpo antifosfolípide e de aloimunidade, a paciente recebeu tratamento com heparina, aspirina e prednisona, além de imunizações com linfócitos. Nas duas gravidezes subseqüentes, teve dois bebês prematuros, que evoluíram com crescimento e desenvolvimento normais. A quinta gravidez não foi bem-sucedida, apesar de a paciente ter recebido um tratamento semelhante ao utilizado previamente embora após o início da gravidez, não planejada. Na discussão deste caso, enfatizamos os mecanismos patogênicos e o tratamento destas doenças.