Relevance of apoptosis in the female reproductive system

La apoptosis es un proceso genéticamente controlado mediante el cual las células inducen su propia muerte. Mensualmente y en forma cíclica, el ovario, el endometrio y la glándula mamaria atraviesan por ciclos de proliferación celular y apoptosis respondiendo a los cambios en la secreción hormonal. Durante el desarrollo embrionario, la apoptosis está implicada en procesos relacionados con la escultura de los diferentes órganos, a través de la eliminación de estructuras innecesarias y con el control de las células defectuosas. Asimismo, la apoptosis juega un papel fundamental en la función ovárica. La reserva folicular se establece durante la vida fetal y luego se va eliminando gradualmente. La apoptosis está involucrada tanto en la muerte celular durante el proceso de reclutamiento del folículo dominante, como en la luteólisis. Durante la pubertad la apoptosis contribuye a la formación del espacio luminal de los ductos terminales de la mama. A su vez, el proceso de involución mamaria luego de la lactancia se caracteriza por una apoptosis masiva de las células epiteliales secretoras. Así como la apoptosis está involucrada en los cambios fisiológicos que ocurren a nivel endometrial, también se ha asociado a la muerte celular programada con procesos patológicos, especialmente en aquellos caracterizados por el incremento en el crecimiento celular como es el caso de la endometriosis. El delicado balance entre la apoptosis y la proliferación celular es fundamental ya que permite que los tejidos puedan responder en forma cíclica a los cambios hormonales fisiológicos y prevenir procesos de transformación neoplásica.Apoptosis is a genetically controlled form of cell suicide. Dueto the cyclic nature of the female reproductive system, the ovary, the endometrium and the mammary gland sustain continuous cycles of cell growth and apoptosis in response to hormonal changes. Apoptotic cell deathplays multiple roles during embryonic and organ development. It is involvedin sculpturing tissues and serves to delete structures that are no longer required. It is clear that apoptosis plays an active and important role in ovarian physiological functions. Apoptosis plays a major role during folliculogenesis and dominant follicle selection and also plays part incorpus luteum regression. In addition, it has been shown that programmed cell death plays important roles in the mammary gland development and ductal morphogenesis. During puberty, lumen formation is associated with the selective apoptosis ofcentrally located cells. In turn, postlactational involution of the mammary gland is characterized by the secretory epithelial cells under going programmed cell death. Apoptosis has also been associated with physiological, aswell as pathological, endometrial processes such as cancer and endometriosis. The delicate balance between apoptosis and cell proliferation is essential incontrolling the cyclical growth of the reproductive tissues and plays an important role in the prevention of neoplastic transformation.Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

I googled. How do you know you\u27re gay? : a qualitative study on LGBTQ identity formation and the Internet /

This qualitative, exploratory study examined the impact of the internet on the identity formation process of LGBTQ individuals. This study aimed to answer the question: How and why do some LGBTQ-identified adults use the internet as a tool to formulate their sexual/gender identity? Through an anonymous online survey, LGBTQ identified participants were asked several open-ended questions about their identity formation experiences, and the role of the internet on this process. Fifty individuals participated in the study, from a wide range of sexual and gender identities, half of which identified as transgender or gender non-conforming. Of these participants, most indicated that the internet was helpful in their identity formation, citing social media, blogs, and e-mail communication as the most commonly used platforms. Participants described the internet as useful for combatting isolation, experimenting and exploring, seeking out information, learning new conceptualizations of identity, and increased authenticity and intimacy. Negative experiences online were also discussed. The research indicated that clinicians working with LGBTQ and questioning clients should bring online efforts into the therapeutic space, and assist clients in managing the risks and benefits of internet use. Areas for further research were suggested

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Prostaglandins are bioactive lipids that possess multiple and diverse functions. In reproductive biology, they are involved in the regulation of ovulation, in endometrial physiology and in the process of menstruation. Furthermore, cyclooxygenases (COX) levels, which are key enzymes for the synthesis of prostaglandins, have been found to be elevated in pathologic, tumoral and inflammatory processes. In endometriosis, prostaglandins are not only implicated in pain, but they are also critical for the establishment as well as for the development of the disease. The high levels of prostaglandin E2 (PGE2) found in the peritoneal fluid from patients with endometriosis, not only favor cellular proliferation by stimulating the activity of aromatase with the consequent estrogen production, but also these estrogens are responsible for enhancing PGE2 synthesis by stimulating COX-2 activity. PGE2 also stimulates angiogenesis and is implicated in the peritoneal immunologic alterations observed in endometriosis. COX-2 inhibitors were and are used in a vast number of preclinical and clinical studies in different types of cancer. In studies conducted both in vitro and in vivo, we have demonstrated that the selective COX-2 inhibitor, celecoxib, was efficient in inhibiting experimental endometriosis. It is important to search for new horizons in endometriosis treatment. Prostaglandins and the enzymes in charge of their synthesis, COXs, represent an attractive target for developing new therapies that attack directly the molecules involved in the causes of this pathology.Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Por despistar de Isidoro Rossi. Un sainete recuperado en el marco de su aniversario 125°

Isidoro Rossi (Paraná, 1897-1951) was the most valuable playwright from Entre Rios of the first half of the twentieth century, for the local scene. The successive premieres by professional companies and philodramatic groups, between 1920 and 1947, either with his pieces or with his performance as a director, made him a fundamental precursor of the provincial independent theatre. His production not only circulated in Entre Ríos, but was known in Rosario, Buenos Aires and Ushuaia. Although most of it remains unpublished or lost, he wrote sainetes criollos, comedies, melodramas, social dramas, plays for children, and a grotesque creole considered in the country an exception of a provincial author. In Por despistar, Rossi makes history again.Isidoro Rossi (Paraná, 1897- 1951) fue el dramaturgo entrerriano más valioso de la primera mitad del siglo XX, para la escena local. Los sucesivos estrenos por compañías profesionales y cuadros o agrupaciones filodramáticas, entre 1920 y 1947, sea con sus piezas o con su desempeño como director, lo convirtieron en un precursor fundamental del teatro independiente provincial. Su producción no sólo circuló por Entre Ríos, sino que fue conocida en Rosario, Buenos Aires y Ushuaia. Pese a que la mayor parte de ella permanece inédita o perdida, escribió sainetes criollos, comedias, melodramas, dramas sociales, piezas de teatro para niños, y un grotesco criollo considerado en el país una excepción de un autor de provincia. En Por despistar, Rossi vuelve a hacer historia

Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients

Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium.Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vighi, Susana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Alfie, Margarita. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Irigoyen, Marcela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Etchepareborda, Juan J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Role of prostaglandins in the pathophysiology of endometriosis

Las prostaglandinas son lípidos bioactivos que poseen múltiples y variadas funciones. En biología reproductiva, participan en la regulación de la ovulación, en la fisiología endometrial y en el proceso de menstruación. Asimismo, los niveles de las ciclooxigenasas (COX), enzimas clave en la producción de prostaglandinas, se han hallado aumentados en procesos patológicos tumorales e inflamatorios. En endometriosis, las prostaglandinas no sólo están implicadas en el dolor, sino que son partícipes clave del desarrollo y establecimiento de la enfermedad. Los altos niveles de prostaglandina E2 (PGE2 ) hallados en el líquido peritoneal de las pacientes con endometriosis, no sólo favorecen la proliferación celular estimulando la actividad de aromatasa con su consiguiente producción de estrógenos, sino que, además, los mismos estrógenos aumentan la síntesis de PGE2 estimulando la actividad de las COX-2. La PGE2 además estimula la angiogénesis y está involucrada en la alteración inmunológica peritoneal que se observa en endometriosis. Los inhibidores de las COX-2 fueron y son actualmente utilizados en numerosos ensayos preclínicos y clínicos en distintos tipos de cáncer. En estudios realizados tanto in vitro como in vivo, hemos demostrado que el inhibidor selectivo de las COX-2, el celecoxib, fue eficaz para inhibir la endometriosis experimental. Resulta importante buscar nuevos horizontes en la terapéutica de la endometriosis. Las prostaglandinas y sus enzimas clave de síntesis, las ciclooxigenasas, representan hoy un blanco atractivo para desarrollar nuevas terapéuticas que ataquen directamente a las moléculas involucradas en las causas de esta patologíaFurthermore, cyclooxygenases (COX) levels, which are key enzymes for the synthesis of prostaglandins, have been found to be elevated in pathologic, tumoral and inflammatory processes. In endometriosis, prostaglandins are not only implicated in pain, but they are also critical for the establishment as well as for the development of the disease. The high levels of prostaglandin E2 (PGE2 ) found in the peritoneal fluid from patients with endometriosis, not only favor cellular proliferation by stimulating the activity of aromatase with the consequent estrogen production, but also these estrogens are responsible for enhancing PGE2 synthesis by stimulating COX-2 activity. PGE2 also stimulates angiogenesis and is implicated in the peritoneal immunologic alterations observed in endometriosis. COX-2 inhibitors were and are used in a vast number of preclinical and clinical studies in different types of cancer. In studies conducted both in vitro and in vivo, we have demonstrated that the selective COX-2 inhibitor, celecoxib, was efficient in inhibiting experimental endometriosis. It is important to search for new horizons in endometriosis treatment. Prostaglandins and the enzymes in charge of their synthesis, COXs, represent an attractive target for developing new therapies that target directly the molecules involved in the causes of this pathologyFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and aromatase proteins have been shown to be overexpressed in eutopic endometrium from women suffering from this disease compared to disease-free women. Furthermore, inhibition of these molecules individually was demonstrated to have antiproliferative and proapoptotic effects both in vitro and in vivo in several models. In this study, the effect of combining celecoxib, a selective COX-2 inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and growth of endometriotic like lesions in a murine model of endometriosis was evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28 days of treatment with celecoxib, anastrozole, or their combination, animals were killed and lesions were counted, measured, excised, and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for assessment of cell proliferation and vascularization. TUNEL technique was performed for apoptosis evaluation. Celecoxib was the only treatment to significantly reduce the number of lesions established per mouse, their size and vascularized area. In addition, cell proliferation was significantly diminished and apoptosis was significantly enhanced by both individual treatments. When the therapies were combined, they reversed their effects. These results confirm that celecoxib and anastrozole separately decrease endometriotic growth, but when combined they might have antagonizing effects.Fil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Ricci, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Barañao, Rosa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

The inhibitory effect of celecoxib and rosiglitazone on experimental endometriosis

To evaluate the effects of celecoxib and rosiglitazone on the implantation and growth of endometriotic-like lesions in a murine model of endometriosis.Fil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ricci, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Barañao, Rosa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55−/− (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at −80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites.Fil: Vallcaneras, Sandra. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ghersa, Federica. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Baston, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Delsouc, María Belén. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Casais, Marilina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; Argentin

Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has anti-proliferative properties and pro-apoptotic effects on different in vivo and in vitro models, two actions that may be efficacious in therapy for endometriosis. We evaluated the effects of celecoxib on apoptosis and proliferation, and vascular endothelial growth factor (VEGF) production and COX-2 expression and activity in endometrial epithelial cells (EECs).Fil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Buque, Ricardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Borghi, Mario. Centro de Estudios en Ginecología y Reproducción; ArgentinaFil: Sueldo, Carlos. Centro de Estudios en Ginecología y Reproducción; ArgentinaFil: Tesone, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin