Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits.

Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.

Infertility in Fabry's Disease: role of hypoxia and inflammation in determining testicular damage.

Introduction: Fabry's disease (FD) is a genetic X-linked systemic and progressive rare disease characterized by the accumulation of globotriaosylceramide (GB3) into the lysosomes of many tissues. FD is due to loss-of-function mutations of α-galactosidase, a key-enzyme for lysosomal catabolism of glycosphingolipids, which accumulate as glycolipid bodies (GB). In homozygous males the progressive deposition of GB3 into the cells leads to clinical symptoms in CNS, skin, kidney, etc. In testis GB accumulation causes infertility and alterations of spermatogenesis. However, the precise damaging mechanism is still unknown. Our hypothesis is that GB accumulation reduces blood vessel lumen and increases the distance of vessels from both stromal cells and seminiferous parenchyma; this, in turn, impairs oxygen and nutrients diffusion leading to subcellular degradation of seminiferous epithelium and sterility. Methods: To test this hypothesis, we have studied a 42-year-old patient presenting a severe FD and infertility, with reduced number of spermatozoa, but preserved sexual activity. Testicular biopsies were analyzed by optical (OM) and transmission electron microscopy (TEM). Activation and cellular localization of HIF-1α and NFκB was analyzed by immunofluorescence (IF) and RT-PCR on homogeneous tissue fractions after laser capture microdissection (LCMD). Results: OM and TEM showed that GB were abundant in vessel wall cells and in interstitial cells. By contrast, GB were absent in seminiferous epithelium, Sertoli's and Leydig's cells. However, seminiferous tubular epithelium and Sertoli's cells showed reduced diameter, thickening of basement membrane and tunica propria, and swollen or degenerated spermatogonia. IF showed an accumulation of HIF-1α in stromal cells but not in seminiferous tubules. On the contrary, NFκB fluorescence was evident in tubules, but very low in interstitial cells. Finally, RT-PCR analysis on LCMD fractions showed the expression of pro-inflammatory genes connected to the HIF-1α/NFκB inflammatory-like pathway. Conclusion: Our study demonstrates that infertility in FD may be caused by reduced oxygen and nutrients due to GB accumulation in blood vessels cells. Reduced oxygen and nutrients alter HIF-1α/NFκB expression and localization while activating HIF-1α/NFκB driven-inflammation-like response damaging seminiferous tubular epithelium and Sertoli's cells.

Minimally invasive delivery of human umbilical cord-derived mesenchymal stem cells by an injectable hydrogel via Diels-Alder click reaction for the treatment of intrauterine adhesions.

Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. STATEMENT OF SIGNIFICANCE: Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.

Dill seed oil as a possible contraceptive agent: antiangiogenic effects on endothelial cells

Abstract Dill (Anethum graveolens L.) essential oil is wide spread in the food, beverage and pharmaceutical sectors. Dill is a member of the Apiaceae (Umbelliferae) family. It has the following biological activities: antioxidant, antifungal, antibacterial, antimicrobial, antihyperlipidemic, antihypercholesterolemic, antispasmodic, antiproliferative and anti-inflammatory. Aqueous extract of dill seed has reported effects on sex hormones and infertility potential. Moreover, boiled dill seed has an impact on reducing labor duration in giving birth. Implantation and placentation are necessary for a healthy pregnancy in the early stages. Angiogenesis is responsible for these essential processes. This study aimed to investigate dill seed oil's cytotoxic and antiangiogenic effects on rat adipose tissue endothelial cells (RATECs). Dill seed oil showed dose-dependent cytotoxicity on RATECs. It disrupted endothelial tube formation and depolymerized F-actin stress fibers. According to this study, depolymerization of F-actin stress fiber by dill seed oil could inhibit angiogenesis by suppressing endothelial cell proliferation, tube formation and motility. In other words, dill seed oil can be a new anti-angiogenic agent and a novel contraceptive.

Pubertad precoz periférica: disgenesia gonadal completa 46 XY / Peripheral precocious puberty: 46, XY complete gonadal dysgenesis

La pubertad precoz, a pesar de las definiciones clínicas estandarizadas y pruebas de diagnóstico disponibles, requiere, en ciertas situaciones una investigación exhaustiva y estructurada con el fin de conocer la causa. Niña de 4 años de edad, fenotípicamente de sexo femenino, enviada a la consulta de endocrinología pediátrica por pubarquia y telarquia. Se observó aceleración en la tasa de crecimiento con niveles altos de estradiol y testosterona, con determinaciones prepúberes de la hormona luteinizante y foliculoestimulante. El resto del estudio de pubertad precoz periférica mostró la presencia de gonadoblastoma bilateral. El estudio genético reveló cariotipo 46 XY con mutación c.89G> T (p.Arg30Ile) en el exón 1 del gen SRY, confirmando el diagnóstico de disgenesia gonadal completa. Los trastornos de la diferenciación sexual deben ser considerados en el abordaje y la investigación de las causas de la pubertad precoz periférica, especialmente en presencia de tumores de ovario, como gonadoblastoma y disgerminomas

Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases. A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89G> T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma

La infertilidad en un área de salud del municipio Cerro / Infertility in a health area of Cerro municipality

OBJETIVOS: caracterizar el comportamiento de la infertilidad en 11 consultorios del Policlínico Héroes de Girón del municipio Cerro. MÉTODOS: se realizó un estudio descriptivo de corte transversal. La selección de los consultorios fue por muestreo por criterios, y los de selección fueron: que tuvieran una distribución equitativa en los Grupos Básicos de Trabajo, así como la estabilidad y conocimiento profundo del área por el personal de enfermería (quien ejecutó la investigación, previa capacitación en el tema). Se aplicaron 2 instrumentos: un formulario a nivel del consultorio y una encuesta a las parejas con problemas por infertilidad. Como medida de resumen se utilizó el porcentaje. RESULTADOS: de un total de 700 parejas en edad fértil que se encontraron, 40 tenían problemas de infertilidad, para un 5,7 por ciento, y de ellas fueron entrevistadas 35. Existió predominio de los factores femeninos, principalmente el tubárico. La mayoría de las parejas estaban en edades óptimas para procrear, con relaciones matrimoniales estables y más de 2 años intentando tener descendencia. Predominó la infertilidad primaria. Más de la mitad de las parejas no tenían seguimiento por esta causa, y las que lo tuvieron, a pesar de ser por más de 3 años, conocen poco la causa de la infertilidad. CONCLUSIONES: la infertilidad en la población estudiada alcanza una mayor magnitud por los problemas de atención, que por la proporción numérica que representa. Se encontró fundamentalmente en edades óptimas para la reproducción, en relaciones estables, con una espera prolongada y con predominio de infertilidad primaria de causa tubárica. Las dificultades diagnósticas y terapéuticas y lo largo del proceso hacen que la mayor parte de las parejas se encuentren insatisfechas con el seguimiento que reciben.

OBJECTIVE: a descriptive cross-sectional study was conducted to characterize the behavior of infertility in 11 family physician's offices of "Héroes de Girón" Polyclinic in Cerro municipality. METHODS: the family physician's offices were chosen by criterion and selection sampling. The selection was based on an equitative distribution in the Basic Working Groups, as well as on the stability and deep knowledge of the area on the part of the nursing personnel that carried out the investigation after being trained on the topic. Two instruments were applied: a questionnaire at the family physician's office level and a survey to the couples with infertility problems, Percentage was used as a summary measure. RESULTS: of a total of 700 couples at fertile age, 40 had infertility problems, accounting for 5.7 percent. 35 of them were interviewed. It was observed a predominance of the female factors, mainly the tubal factor. Most of the couples were at optimal ages to procreate with steady marriage relations and they had been trying to have children for more than 2 years. Primary infertility prevailed. More than half of the couples were not followed up for this reason, and those who were, in spite of being followed up for more than 3 years, knew little about the cause of infertility. CONCLUSIONS: infertility in the studied population reaches a greater magnitude due to the problems of attention rather than for the figure it represents. It was mainly found at optimal ages for reproduction, in stable relations with a prolonged waiting and with predominance of primary tubal infertility. The diagnostic and therapeutic difficulties, as well as the long process make that most of the couples be unsatisfied with the follow-up they recieve.

La infertilidad en un área de salud del municipio Cerro / Infertility in a health area of Cerro municipality

OBJETIVOS: caracterizar el comportamiento de la infertilidad en 11 consultorios del Policlínico Héroes de Girón del municipio Cerro. MÉTODOS: se realizó un estudio descriptivo de corte transversal. La selección de los consultorios fue por muestreo por criterios, y los de selección fueron: que tuvieran una distribución equitativa en los Grupos Básicos de Trabajo, así como la estabilidad y conocimiento profundo del área por el personal de enfermería (quien ejecutó la investigación, previa capacitación en el tema). Se aplicaron 2 instrumentos: un formulario a nivel del consultorio y una encuesta a las parejas con problemas por infertilidad. Como medida de resumen se utilizó el porcentaje. RESULTADOS: de un total de 700 parejas en edad fértil que se encontraron, 40 tenían problemas de infertilidad, para un 5,7 por ciento, y de ellas fueron entrevistadas 35. Existió predominio de los factores femeninos, principalmente el tubárico. La mayoría de las parejas estaban en edades óptimas para procrear, con relaciones matrimoniales estables y más de 2 años intentando tener descendencia. Predominó la infertilidad primaria. Más de la mitad de las parejas no tenían seguimiento por esta causa, y las que lo tuvieron, a pesar de ser por más de 3 años, conocen poco la causa de la infertilidad. CONCLUSIONES: la infertilidad en la población estudiada alcanza una mayor magnitud por los problemas de atención, que por la proporción numérica que representa. Se encontró fundamentalmente en edades óptimas para la reproducción, en relaciones estables, con una espera prolongada y con predominio de infertilidad primaria de causa tubárica. Las dificultades diagnósticas y terapéuticas y lo largo del proceso hacen que la mayor parte de las parejas se encuentren insatisfechas con el seguimiento que reciben(AU)

OBJECTIVE: a descriptive cross-sectional study was conducted to characterize the behavior of infertility in 11 family physician's offices of "Héroes de Girón" Polyclinic in Cerro municipality. METHODS: the family physician's offices were chosen by criterion and selection sampling. The selection was based on an equitative distribution in the Basic Working Groups, as well as on the stability and deep knowledge of the area on the part of the nursing personnel that carried out the investigation after being trained on the topic. Two instruments were applied: a questionnaire at the family physician's office level and a survey to the couples with infertility problems, Percentage was used as a summary measure. RESULTS: of a total of 700 couples at fertile age, 40 had infertility problems, accounting for 5.7 percent. 35 of them were interviewed. It was observed a predominance of the female factors, mainly the tubal factor. Most of the couples were at optimal ages to procreate with steady marriage relations and they had been trying to have children for more than 2 years. Primary infertility prevailed. More than half of the couples were not followed up for this reason, and those who were, in spite of being followed up for more than 3 years, knew little about the cause of infertility. CONCLUSIONS: infertility in the studied population reaches a greater magnitude due to the problems of attention rather than for the figure it represents. It was mainly found at optimal ages for reproduction, in stable relations with a prolonged waiting and with predominance of primary tubal infertility. The diagnostic and therapeutic difficulties, as well as the long process make that most of the couples be unsatisfied with the follow-up they recieve(AU)

Accuracy of laparoscopy for assessing patients with endometriosis / Eficácia da videolaparoscopia na avaliação de mulheres com endometriose pélvica

CONTEXT AND OBJECTIVE: Diagnoses of endometriosis are based on observation of endometriotic lesions by means of laparoscopy, along with the pathological findings. The aim of this study was to evaluate the sensitivity and specificity of the macroscopic findings in relation to the histopathological findings. More specifically, we aimed to test the efficacy of laparoscopy alone for diagnosing endometriosis and to evaluate the laterality of endometriosis among the study population. DESIGN AND SETTING: Cross-sectional study on women undergoing laparoscopy due to pelvic pain or infertility, in the Gynecology Department of Hospital Santa Cruz in Curitiba, Paraná, Brazil, and Pontifícia Universidade Católica do Paraná. METHODS: A total of 976 patients underwent laparoscopy and biopsy due to pelvic pain and/or infertility. We analyzed the laparoscopic and histopathological findings from patients with pelvic endometriosis (n = 468) and patients without endometriosis (n = 508). RESULTS: In 468 (47.95 percent) of the cases, the clinical and laparoscopic findings were consistent with endometriosis, and this was confirmed histopathologically in 337 (34.5 percent). Among the remaining 508 patients, although the laparoscopy was performed for other reasons relating to acute pelvic pain, eight were diagnosed with endometriosis from histopathological examination of the pelvic specimens obtained. Therefore, endometriosis was confirmed in 345 patients (35.3 percent). In comparison with the histopathology, laparoscopy alone presented 97.68 percent sensitivity, 79.23 percent specificity, 72 percent positive predictive value and 98.42 percent negative predictive value. CONCLUSION: Laparoscopy should be used in conjunction with histopathology for diagnosing endometriosis.

CONTEXTO E OBJETIVO: O diagnóstico da endometriose é determinado pela visualização dos implantes à laparoscopia e pela comprovação histológica. O objetivo deste trabalho foi avaliar a sensibilidade e a especificidade dos achados macroscópicos cirúrgicos e histopatológicos. Avaliou-se a eficácia da laparoscopia isoladamente no diagnóstico da endometriose e a lateralidade da doença. TIPO DE ESTUDO E LOCAL: Estudo transversal realizado no Serviço de Ginecologia do Hospital Santa Cruz em Curitiba, Paraná e na Pontifícia Universidade Católica do Paraná. MÉTODOS: Foram avaliadas 976 pacientes submetidas à videolaparoscopia por dor pélvica ou infertilidade e a biópsia. Foram analisados os achados laparoscópicos e histológicos de 468 pacientes com endometriose pélvica e de 508 pacientes sem endometriose. RESULTADOS: Foram selecionadas 468 (47,95 por cento) pacientes para inclusão no presente estudo por apresentarem quadro clínico e videolaparoscópico de suspeita de endometriose. As 508 (52,04 por cento) pacientes restantes tiveram indicação da cirurgia por outras causas relacionadas à dor pélvica e oito tiveram o diagnóstico de endometriose pelo anatomopatológico. A endometriose foi confirmada em 345 pacientes (35,3 por cento). Ao compararmos a análise histológica com os achados a videolaparoscopia, observou-se sensibilidade de 97,68 por cento, especificidade de 79,23 por cento, valor preditivo positivo de 72 por cento, valor preditivo negativo de 98,42 por cento. CONCLUSÃO: Laparoscopia deve ser usada em conjunto com histopatologia para o diagnóstico de endometriose.

Seroepidemiología de la rinotraqueitis infecciosa bovina en el municipio de Montería, Colombia / Seroepidemiology of the infectious bovine rhinotracheitis in the municipality of Montería, Colombia

Objetivo. Estudiar la sero prevalencia de IBR en ganado bovino con antecedentes de infertilidad. Materiales y métodos. Se recolectaron 150 muestras de sangre de hembras con antecedentes de infertilidad y sin historia de vacunación contra IBR, pertenecientes a 32 fincas distribuidas en el municipio de Montería. adicionalmente, se obtuvieron muestras al azar de 20 toros pertenecientes a las mismas fincas. Se analizaron anticuerpos contra IBR mediante la prueba de ELISA. Resultados. Los resultados mostraron una seroprevalencia de 74.7 por ciento para rinotraqueitis infecciosa bovina. Seencontraron diferencias significativas en cuanto a prevalencía para las variables sexo y edad de los animales (p<0.05). No hubo diferencias significativas en prevalencía para las variables raza, zona, tipo de explotación y alteraciones reproductivas (p>0.05). Conclusión. La alta prevalencia de la infección por IBR en vacas podrían correlacionarse con la infección en toros, lo cual tiene un significado relevante, ya que la infección es de transmisión venérea. Estos resultados deben alertar a las autoridades sanitarias para que implementen estrategias de prevención y control

Objective. To study the seroprevalence of IBR in livestock bovine with infertility antecedents. Materials and methods. Blood samples were collected from 150 animals with infertility antecedents and nonvaccinated history against IBR, belonging to 32 farms in Monteria municipality and samples at random of 20 bulls belonging to the same farms. Antibodies were analyzed against IBR by using ELISA test. Results. The results showed a seroprevalence of 74.7% for bovine rhinotracheitis infectious. They were significant differences with regard to prevalence for sex and age variables of animals (p<0.05). There were not significant differences in prevalence for the variable race, area, type of exploitation and reproductive alterations (p>0.05). Conclusion. The high prevalence of the infection for IBR in cows could be associated with the infection in bulls, which has an outstanding meaning, since the infection is of venereal transmission. These results should alert to sanitary authorities in order to implement prevention and control strategies.

Endometriosis del íleon como causa de obstrucción intestinal: Report of two cases / Ileal endometriosis as a cause of intestinal obstruction. Report of two cases

Endometriosis is a common, chronic, benign, estrogen dependent gynecological disorder associated to pelvic pain and infertility. Its main characteristic is the presence of endometrial tissue outside the uterus. The prevalence of pelvic endometriosis ranges between 6% and 10% women during their reproductive years. Clinical symptoms of pelvic endometriosis are pelvic pain, dysmenorrhea, dispareunia and infertility. Distal ileum endometriosis is an uncommon cause of intestinal obstruction with a frequency of 7% to 23% of all cases with intestinal involvement. We report two patients, 30 and 34 years old, with terminal ileum endometriosis and intestinal obstruction that required surgery and intestinal resection. Both patients are well one year after the operation.

El endometrio en la infertilidad: histología y fechado endometrial

El procedimiento de la biopsia de endometrio es muy discutido para el diagnóstico de ovulación máxime si se relaciona con la determinación de la progesterona en sangre. Sinembargo en nuestra experiencia consideramos este procedimiento muy útil, no sólo para aproximarse al diagnóstico de cuerpo lúteo insuficiente sino para diagnosticar otras patologías tales como estenosis y pólipos endocervicales, además de patología uterina y endometrial macro o microscópica. Se hace una descripción breve sobre los fenómenos que ocurren durante el proceso de maduración endometrial a lo largo del ciclo mestrual y los diferentes patrones utilizados para el fechado endometrial; finalmente se propone un método objetivo para medir la maduración endometrial, útil para la investigación, basándose en la medición de variables cualitativas que hacen parte de los cambios a través del ciclo

El embarazo ectópico en pacientes estériles / Ectopic pregnancy in sterile patients

Se revisan los estudios ecográficos de cuarenta pacientes privadas con sospecha de embarazo ectópico (EE), lograndose el seguimiento en veintitrés de ellas. En doce de ellas la ecografía coincidió con la clínica, confirmándose en la cirugía diez de ellos. En los otros dos se trataba de un tumor de ovario y un mioma pediculado torcido. Dos casos catalogados como teratoma de ovario y ovario aumentado de volumen, resultaron ser EE. Se diagnósticó y descartó EE en el 33% de los casos. Se concluye que el ultrasonido debe ser el primer paso a realizar en sospecha de gestación ectópica para evitar operaciones innecesarias