Cushing disease due to a somatic USP8 mutation in a patient with evolving pituitary hormone deficiencies due to a germline GH1 splicing variant

SUMMARY We present the unique case of an adult Brazilian woman with severe short stature due to growth hormone deficiency with a heterozygous G to T substitution in the donor splice site of intron 3 of the growth hormone 1 (GH1) gene (c.291+1G>T). In this autosomal dominant form of growth hormone deficiency (type II), exon 3 skipping results in expression of the 17.5 kDa isoform of growth hormone, which has a dominant negative effect over the bioactive isoform, is retained in the endoplasmic reticulum, disrupts the Golgi apparatus, and impairs the secretion of other pituitary hormones in addition to growth hormone deficiency. This mechanism led to the progression of central hypothyroidism in the same patient. After 5 years of growth and thyroid hormone replacement, at the age of 33, laboratory evaluation for increased weight gain revealed high serum and urine cortisol concentrations, which could not be suppressed with dexamethasone. Magnetic resonance imaging of the sella turcica detected a pituitary macroadenoma, which was surgically removed. Histological examination confirmed an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma. A ubiquitin-specific peptidase 8 (USP8) somatic pathogenic variant (c.2159C>G/p.Pro720Arg) was found in the tumor. In conclusion, we report progression of isolated growth hormone deficiency due to a germline GH1 variant to combined pituitary hormone deficiency followed by hypercortisolism due to an ACTH-secreting macroadenoma with a somatic variant in USP8 in the same patient. Genetic studies allowed etiologic diagnosis and prognosis of this unique case.

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies / 医学前沿

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

Identification of a novel germline BRCA2 variant in a male with breast cancer / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a male with breast cancer and a sister who had deceased of the disease.@*METHODS@#Medical and family history of the proband was collected. Next-generation sequencing was carried out to detect potential variant associated with breast cancer, and Sanger sequencing was used to verify the result.@*RESULTS@#The proband was found to harbor a novel heterozygous c.6018dupT variant of the BRCA2 gene which may cause premature termination of mRNA translation, resulting in a truncated protein. Combined with the family history, the variant was deduced to be a germline mutation. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.6018dupT variant of BRCA2 gene was predicted to be pathogenic (PVS1+PM1/2+PP4).@*CONCLUSION@#The germline variant of the BRCA2 gene probably underlay the breast cancer in this pedigree.

El consumo semicrónico moderado de alcohol altera la foliculogénesis y la calidad núcleo-citoplasmática oocitaria, en el ratón / Moderate semi-chronic alcohol consumption alters folliculogenesis and oocyte nuclear-cytoplasmic quality in mice

Resumen El consumo crónico de alcohol es un problema de salud mundial que afecta particularmente a la población femenina. Sin embargo, los efectos de la ingesta semicrónica en cantidades moderadas a bajas en el ovario y el oocito son poco conocidos. En un modelo murino, se administró etanol al 10% en agua de bebida (hembras tratadas) o agua (hembras control) por 15 días, y luego de la superovulación o no (ovulación espontánea), se analizó el ciclo estral y la calidad ovárico-gamética. En las hembras tratadas, la frecuencia y duración del diestro aumentó, y las frecuencias de folículos y cuerpos lúteos disminuyeron vs hembras controles, valores que se restauraron luego de la superovulación. Sin embargo, en las hembras tratadas, la tasa de proliferación celular folicular y el desbalance de la expresión ovárica de VEGF (factor de crecimiento endotelial) persistieron luego de la superovulación. El número de ovocitos ovulados con metafase II anormal, fragmentados y activados partenogenéticamente fue mayor en las hembras tratadas respecto las controles. En conclusión, el consumo semicrónico moderado de alcohol produce anestro, ciclo estral irregular, foliculogénesis deficiente y anomalías núcleo-citoplasmáticas en los oocitos ovulados. Estas alteraciones podrían constituirse en un factor etiológico de pérdida gestacional temprana y desarrollo embrionario anormal luego del consumo de alcohol.

Abstract Chronic alcohol consumption is a global health problem that particularly affects the female population. However, the ef-fects of semi-chronic ethanol intake in low-moderate amounts on the ovary and oocyte are poorly understood. In a mouse model, 10% ethanol was administered in drinking water (treated females) or water (control females) for 15 days, and after superovulation or not (spontaneous ovulation), the estrous cycle and ovarian-gametic quality were analyzed. In treated females, the frequency and duration of the diestrus increased, and the frequencies of follicles and corpus luteum decreased vs control females, values that restored after superovulation. However, in treated females, the follicular cell proliferation rate and the imbalance in ovarian expression of VEGF (endothelial growth factor) persisted after superovulation. The number of ovulated oocytes with abnormal metaphase II, fragmented and parthenogenetically activated was higher in treated females than in control ones. In conclusion, moderate semi-chronic alcohol consumption produces anestrum, irregular estrous cycle, poor folliculogenesis, and nuclear-cytoplasmic abnormalities in ovulated oocytes. These alterations could constitute an etiological factor of early gestational loss and abnormal embryonic development after alcohol consumption.

Manejo de pacientes con tumores de células germinales en primera recaída / Management of patients with germinal cell tumors in first relapse

Resumen Los tumores de células germinales (TCG) son las neoplasias malignas más comunes y afectan especialmente a hombres jóvenes de 15 a 35 años de edad. Los pacientes con estadios 2 y 3 que recaen ofrecen un gran reto para el tratamiento inicial de la primera recaída. La terapia óptima para estos pacientes depende de su tratamiento inicial y está pobremente definida. Las opciones incluyen regímenes de segunda línea de quimioterapia a dosis convencionales que combinan cisplatino e ifosfamida, con vinblastina, etopósido o paclitaxel, o quimioterapia de altas dosis con soporte de células madre. En vista de que todavía no hay evidencia concluyente en los ensayos clínicos, las indicaciones para el uso de quimioterapia de altas dosis permanecen poco claras y se basan en estudios fundamentalmente retrospectivos. El tratamiento en la segunda recaída debe individualizarse según el paciente y el tratamiento previo. La resección quirúrgica de masas residuales luego de la quimioterapia es un elemento clave para una terapia exitosa en pacientes con marcadores tumorales negativos. Actualmente, en Venezuela los pacientes que presentan recaídas deben recibir tratamiento con cualquiera de los regímenes establecidos que se utilizan a dosis convencionales en segunda línea. En algunos casos, los pacientes deben recibir tratamiento en centros de oncología con un manejo multidisciplinario que permita el acceso a tratamiento con altas dosis de quimioterapia y a cirujanos oncólogos expertos en esta patología.

Abstract Germ cell tumors (GCT) are the most common malignant neoplasms affecting young men aged 15 to 35 years. Patients with previous stage 2 and 3 who relapse offer a great challenge to the Medical team. The optimal therapy for these patients with recurrent disease is still poorly defined. Options include second-line chemotherapy regimens at conventional doses which combine cisplatin and ifosfamide, with vinblastine, etoposide or paclitaxel, or alternatively high-dose chemotherapy with stem cell support. As there is still no conclusive evidence from clinical trials, the indications for the use of high-dose chemotherapy remain unclear. Most of the present literature is based in retrospective studies. Second relapse treatment options should be individualized according to the patient and his previous treatment. Surgical resection of residual masses in patients with negative markers after chemotherapy is a key element for successful therapy. Currently, patients in Venezuela who have relapses should receive treatment with any of the established regimens that are used at conventional doses in the second line, however in some cases they should receive treatment in an oncology center with a multidisciplinary team having access to treatment with high dose chemotherapy and to oncologist surgeons who are experts in this area.

The Right to Be Forgotten versus the Right to Disclosure of Gamete Donors' ID: Ethical and Legal Considerations / El derecho al olvido frente al derecho a revelar la identificación de los donantes de gametos: consideraciones éticas y jurídicas / O Direito ao Esquecimento versus o Direito à Divulgação da Identificação de Dadores de Gâmetas: Considerações Éticas e Legais

Abstract: 15. The anonymity of gamete donors in the context of medically-assisted reproduction techniques (ART) and the right of the offspring to know their genetic or biological parents' identity is a controversial and widely debated topic in the scientific literature. The positions on the issue in each country are different. Sometimes they are in opposition to each other even in countries with strong similarities, such as those in the European Union (EU), in the framework of shared ethical values. Although some countries still enshrine the rule of anonymity, there is an undeniable tendency to guarantee the right to know one's origins by creating relevant exceptions or abolishing donor anonymity status altogether. 16. This article offers ethical and legal considerations of whether the so-called 'right to be forgotten' (RTBF) could be extended to include gamete donors' right to remain anonymous. This perspective goes against the general trend, certainly in Europe, of recognizing that offspring born from donor gametes have a right to access information relating to their genetic progenitors. The novel addition is to question whether the General Data Protection Regulation (GDPR) might provide fertile ground for questioning this approach, and effectively support those jurisdictions where anonymity is still possible.

Resumen: 20. El anonimato de los donantes de gametos en el contexto de las técnicas de reproducción médicamente asistida (RM) y el derecho de la descendencia a conocer su identidad genética o biológica es un tema controvertido y ampliamente debatido en la literatura científica. Las posiciones sobre el tema en cada país son diferentes. A veces se oponen entre sí, incluso en países con fuertes similitudes, como los de la Unión Europea (UE), en el marco de valores éticos compartidos. Aunque algunos países siguen consagrando la norma del anonimato, es innegable la tendencia a garantizar el derecho a conocer el propio origen creando las excepciones pertinentes o suprimiendo por completo el estatus de anonimato del donante. 21. Este artículo ofrece consideraciones éticas y jurídicas sobre si el llamado "derecho al olvido" podría ampliarse para incluir el derecho de los donantes de gametos a permanecer en el anonimato. Esta opinión es contraria a la tendencia general, ciertamente en Europa, de reconocer que los hijos nacidos de gametos donados tienen derecho a acceder a la información relativa a sus padres genéticos. La nueva adición consiste en debatir si el Reglamento general de protección de datos (RGPD) podría proporcionar un terreno fértil para cuestionar este enfoque y apoyar efectivamente a las jurisdicciones en las que el anonimato sigue siendo posible.

Resumo 25. O anonimato dos dadores de gâmetas no contexto das técnicas de reprodução medicamente assistida (RMA) e o direito da descendência a conhecer a sua identidade genética ou biológica é um tema controverso e amplamente debatido na literatura científica. As posições sobre a questão em cada país são diferentes. Por vezes estão em oposição umas às outras, mesmo em países com fortes semelhanças, como os da União Europeia (UE), no quadro de valores éticos partilhados. Embora alguns países ainda consagrem a regra do anonimato, existe uma tendência inegável para garantir o direito de conhecer as suas origens, criando exceções relevantes ou abolindo completamente o estatuto de anonimato dos dadores. 26. Este artigo oferece considerações éticas e legais sobre se o chamado "direito ao esquecimento" poderia ser alargado para incluir o direito dos dadores de gâmetas a permanecerem anónimos. Esta perspetiva vai contra a tendência geral, certamente na Europa, de reconhecer que os descendentes nascidos de gâmetas doadas têm o direito de aceder à informação relacionada com os seus progenitores genéticos. O novo aditamento é debater se o Regulamento Geral de Proteção de Dados (RGPD) poderá fornecer um terreno fértil para questionar esta abordagem, e apoiar efetivamente as jurisdições onde o anonimato ainda é possível.

Germline and Somatic mutations in postmenopausal breast cancer patients

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Advances in research on the development of female germ cells / 中华医学遗传学杂志

The development of female germ cells can be mainly divided into two stages: fetal germ cells and oocytes in folliculogenesis after puberty. Mitosis-meiosis transition, meiosis arrest and re-activation are the key phases of the development. Several phases may be characterized by their distinct molecular events, which involve precise regulation of gene expression and interaction with corresponding gonadal niche cells. In recent years, single-cell transcriptome studies have clarified phase-specific patterns of gene expression, signaling pathways and epigenetic modification during oogenesis and folliculogenesis. These works have provided important insights into the development of female germ cells and pathogenesis of germ-cell related diseases, which may promote clinical application of reproductive genetic research.

Autism spectrum disorder/development delay in siblings with SCN2A mutations caused by germline mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To report on a family which has two siblings with SCN2A mutation caused by germline mosaicism suffering from autism spectrum disorder/development delay (ASD/DD).@*METHODS@#Clinical data was collected for the proband and his parents. Next generation sequencing (NGS) was carried out on the proband and his parents. Suspected mutations were verified by Sanger sequencing of the proband, his parents and brother. To detect whether there is a low proportion of somatic mosaicism in the parents, a droplet digital PCR was conducted. The result of ddPCR showed that the father was germline mosaicism (0.233%).@*RESULTS@#NGS has identified a de novo splicing mutation of the SCN2A gene, c.605+1G>A, in the proband and his brother. Combined with its clinical phenotype and inheritance pattern, SCN2A was judged to be the pathogenic gene. Above findings strongly suggested parental germline mosaicism.@*CONCLUSION@#ASD/DD in siblings with SCN2A mutations caused by germline mosaicism. Paternal mosaicism should be considered as one of the important inheritance patterns for counseling parents with a child carrying SCN2A mutation. The ddPCR can help to reveal very low proportion of germline mosaicism.

The morphology of paca (Cuniculus paca) testis with high dose of letrozole an aromatase inhibitor / La morfología del testículo de paca (Cuniculus paca) con altas dosis de letrozol, un inhibidor de la aromatasa

SUMMARY: The study reported the influence of the high and acute dose of Letrozole on the testis morphology in paca (Cuniculus paca), an aromatase inhibitor that reduces the endogenous estrogen, the essential hormone for spermatogenesis. Morphological changes were observed in seminiferous epithelium with germ cells with apoptotic characteristics and presence of vacuoles and nuclei in pycnose.

RESUMEN: El objetivo de este estudio fue analizar la influencia de una dosis alta de Letrozol en la morfología de los testículos de la paca (Cuniculus paca), un inhibidor de la aromatasa que reduce el estrógeno endógeno, la hormona esencial para la espermatogénesis. Se observaron cambios morfológicos en el epitelio seminífero con células germinales con características apoptóticas y la presencia de vacuolas y núcleos en picnosis.

Disgerminoma de ovario con componente sincitiotrofoblástico en una adolescente / Ovarian dysgerminoma with syncythiotrophlastic component in a teenage woman

INTRODUCCIÓN. Los tumores de células germinales del ovario de carácter maligno son infrecuentes en la adolescencia. Los disgerminomas se caracterizan por crecimiento rápi-do, diseminación linfática, alta sensibilidad a la radioterapia y quimioterapia. OBJETIVO. Establecer la presentación clínica, métodos diagnósticos y tratamiento para el manejo del disgerminoma ovárico en una adolescente. CASO CLÍNICO. Paciente mestiza de 14 años que acudió por dolor abdominal y masa palpable en región abdominopélvica asociados a elevación de marcadores séricos tumorales. Los reportes de imagen informaron masa ane-xial derecha, sólida de bordes lobulados y bien definidos. RESULTADOS. Se realizó exére-sis del tumor con protocolo de ovario conservador. El postoperatorio describió tumor ovári-co de 20 cm, lobulado y sólido que comprometió el ovario derecho en toda su extensión. El estudio histopatológico reportó: disgerminoma en estadio patológico IA moderadamente diferenciado, con extensión tumoral a pared de la trompa uterina derecha. DISCUSIÓN. El caso coincidió con otros reportes descritos en la literatura, donde la presentación clínica fue similar y el abordaje terapéutico con un protocolo de ovario conservador más la quimio-terapia adyuvante fueron la elección más óptima para preservar la función endocrina y la fertilidad en la paciente. CONCLUSIÓN. Los exámenes complementarios para determinar el diagnóstico fueron los marcadores tumorales, la ecografía pélvica y la tomografía axial computarizada simple y contrastada de abdomen y pelvis. La cirugía conservadora abierta es gold standard complementada con quimioterapia adyuvante en la adolescente.

INTRODUCTION. Germ cells tumors of the ovary of a malignant nature are uncommon in the adolescence. Dysgerminomas are characterized by rapid growth, lymphatic disse-mination, high sensitivity to radiotherapy and chemotherapy. OBJECTIVE. Establish the clinical presentation and diagnostic methods of ovarian dysgerminoma in the pediatric age for a correct therapeutic approach. CLINICAL CASE. A mestiza female of 14 years old, who has abdominal pain and a palpable mass in the abdominal pelvic region, and also elevation of the serum tumor markers. Image reports showed right solid adnexal mass with well-defined lobed edges. RESULTS Tumor exeresis was performed with a conservative ovarian protocol. The postoperative findings described a 20 cm, lobulated, solid ovarian tumor that compromised the right ovary in its entirety. The histopathological study repor-ted: moderately differentiated pathological stage dysgerminoma IA, with tumor extension to the wall of the right uterine tube. DISCUSSION. The case agrees with other reports described in the literature where the clinical presentation was similar and the therapeutic approach with a conservative ovary protocol plus adjuvant chemotherapy were the most optimal choice to preserve endocrine function and fertility in the patient. CONCLUSION. The complementary exams to reach the diagnosis were tumor markers, pelvic ultrasound and simple and contrasted computarized axial tomography of the abdomen and pelvis. Open conservative surgery was the gold standard supplemented with adjuvant chemothe-rapy in adolescent.

Factores asociados a la histología de masa residual retroperitoneal post quimioterapia en tumor testicular de células germinales / Factors Associated with the Histology of Retroperitoneal Residual Mass Post Chemotherapy in Testicular Germ Cell Tumo

Objetivo El objetivo de este estudio es describir las características y factores relacionados con la histología de la masa residual postquimioterapia en pacientes con tumor de células germinales de origen testicular sometidos a linfadenectomía retroperitoneal durante 12 años de seguimiento. Métodos Retrospectivamente se recolectaron datos clínicos, quirúrgicos y patológicos de la historia clínica de los pacientes en un centro de referencia de manejo de cáncer durante un periodo de 12 años. Se estimó la asociación entre los datos recolectados con la histología del tumor residual post quimioterapia. Resultados Se incluyeron 64 pacientes, la edad promedio fue 28.1 años, el tamaño promedio de masa residual fue de 6.7 cm. La histología de la masa residual fue teratoma en 60.9%, necrosis 26.5% y tumor viable 12.5%. El grupo pronóstico tiene asociación con la histología de la masa retroperitoneal. Las masas con histología de necrosis tuvieron menor tamaño con media 6.5 cm mientras que otras histologías tuvieron tamaño promedio de la masa residual de 10.4 cm. Conclusiones La LNDRP-PC es el estándar de tratamiento en masas residuales retroperitoneales después de quimioterapia y puede generar sobre-tratamiento hasta en 50% de los casos. El teratoma en la histología testicular está relacionado mayor tamaño de la masa residual retroperitoneal. Las características histológicas de la masa residual son comparables con otras series.

Objective The aim of the study is to describe factors and characteristics related with the post-chemotherapy residual mass histology in patients who undergoing RPLND. Methods Clinical, surgical and pathological data were retrospectively recorded from medical records of patients with diagnosis of germ cell tumor and post-chemotherapy residual retroperitoneal tumor in a cancer referral center over a period of 12 years. The association between the data collected and the post-chemotherapy residual tumor histology was assessed. Results Sixty-four patients were included with average age of 28.1 years. The mean residual mass size was 6.7 cm. The histology of the mass was teratoma in 60.9%, necrosis 26.5% and viable tumor 12.5%. Prognostic group was associated with the mass histology. Mass with necrosis histology was smaller with mean size of 6.5 cm, while other histologies had an average mass size of 10.4 cm. Conclusion PC-RPLND is the standard of management of retroperitoneal residual mass after chemotherapy and could over treat in up to 50% of cases. Teratoma component in testicular histology is related to increase size of the residual mass. Histology findings of the retroperitoneal mass are comparable with other series.

MIME-Mitosis instead of meiosis and its application in crop apomixis / 生物工程学报

Apomixis has been widely concerned because of its great potential in heterosis fixation. Artificial apomixis is an important direction of current apomixis research. Mitosis instead of Meiosis (MIME) produces diploid gametes that is identical with the maternal genetic composition and is a key step in the artificial creation of apomixes. This paper reviews the occurrence of MIME and its application in crop apomixis and the problems encountered, in an aim to provide reference for expanding the application of MIME in crop apomixis.

Ovarian dysgerminoma causing multifocal metastases in young bitch / Disgerminoma ovariano causando metástases multifocais em cadela jovem

The ovarian neoplasias are unusual in canine species, mainly originated from germinative cells. Among these, dysgerminoma is a rare neoplasm in bitches, predominantly affecting senile and small and medium breeds. They are large, rounded, smooth surface, painless and firm in consistency. The clinical signs commonly demonstrated by patients with this neoplasia are abdominal distension and secondary signs of hyperestrogenism. The diagnosis should be based on the association of history, clinical signs, radiographic, ultrasonographic, cytological, histopathological and immunohistochemical exams. The treatment is the surgical castration and metastases are uncommon. Due to the rarity in bitches, specifically the young animals, this study aimed to describe a case of left ovarian dysgerminoma, of considerable size and adherence in adjacent organs, in a Brazilian Fila, whose showed considerable increase in abdominal volume and progressive weight loss. The diagnosis was confirmed by means of complementary x-ray, ultrasound, histopathological and immunohistochemical tests. Even with the recommended surgical treatment (castration), the patient demonstrated severe respiratory symptoms and increased abdominal volume after two months, and the complementary exams suggested pulmonary and multifocal metastases and the tutor chose euthanasia. As presented by the results, although rare in bitches, dysgerminoma should be included in the differential of ovarian neoplasias, including the young ones.

As neoplasias ovarianas são de ocorrência incomum na espécie canina, principalmente as originadas de células germinativas. Dentre estas, o disgerminoma é uma neoplasia rara em cadelas, acometendo predominantemente fêmeas senis e de raças pequenas e médias. Apresentam-se como massas grandes, arredondadas, de superfície lisa, indolores e de consistência firme. Os sinais clínicos comumente demonstrados por pacientes com este tipo neoplásico incluem distensão abdominal e sinais secundários de hiperestrogenismo. O diagnóstico deve ser baseado na associação do histórico, sinais clínicos, exames radiográficos, ultrassonográficos, citológicos, histopatológicos e imunohistoquímicos. O tratamento de escolha é a castração cirúrgica, sendo que as metástases são incomuns. Perante a raridade em cadelas, em específico as jovens, este relato teve como propósito discorrer um caso de disgerminoma ovariano esquerdo, de tamanho considerável e aderência em órgãos adjacentes, em uma Fila Brasileira, cuja sintomatologia incluiu considerável aumento de volume abdominal e emagrecimento progressivo. O diagnóstico foi confirmado por meio de exames complementares de raios-x, ultrassom, histopatológico e imunohistoquímicos. Mesmo com a instituição dotratamento cirúrgico preconizado (castração), a paciente demonstrou grave sintomatologia respiratória e aumento de volume abdominal após dois meses e, como os exames complementares foram sugestivos de metástases pulmonares e multifocais, o tutor optou pela eutanásia. Diante dos resultados, pode-se admitir que apesar de raro em cadelas, o disgerminoma deve ser incluído no diferencial das neoplasias ovarianas, incluindo as jovens.

Teratocarcinoma gigante de mediastino anterosuperior / Giant teratocarcinoma of anterosuperior mediastinum

RESUMEN Los tumores de células germinales no son tan frecuentes, dentro de ellos se encuentra el teratoma como el más usual en ubicación mediastinal, es más habitual en hombres jóvenes cuando es maligno (teratocarcinoma), con una relación por género de 13,5:1, y una edad promedio de 26 años. Se describe la evolución de un hombre de 19 años de edad con un tumor mediastinal, con metástasis pulmonares e infiltración intracardíaca, resecado satisfactoriamente, cuyos síntomas más frecuentes fueron: disnea, dolor retroesternal, fiebre, tos, pérdida de peso y síndrome de vena cava superior. El diagnóstico se realizó por radiografía de tórax y tomografía axial computarizada. Se logró realizar la excéresis total del tumor y las metástasis, así como la tumoración intracardíaca, con reparación de la válvula tricúspide. El paciente ha tenido una evolución satisfactoria durante el primer año de seguimiento.

ABSTRACT Germ cell tumors are not so frequent; among them, teratomas are most common in the mediastinal location. Teratomas in young men are usually malignant (teratocarcinoma), with a gender ratio of 13.5:1, and an average age of 26 years. We describe the evolution of a 19-year-old man with a mediastinal tumor, with pulmonary metastases and intracardiac infiltration, successfully removed; whose most frequent symptoms were: dyspnea, retrosternal pain, fever, cough, weight loss and superior vena cava syndrome. The diagnosis was made by chest x-ray and computed tomography. Total removal of the tumor and metastases was achieved, as well as the intracardiac tumor, with tricuspid valve repair. The patient had a satisfactory outcome during the first follow-up year.

Effects of paternal age on human embryo development in in vitro fertilization with preimplantation genetic screening / 대한생식의학회지

OBJECTIVE: As paternal age increases, the quality of sperm decreases due to increased DNA fragmentation and aneuploidy. Higher levels of structural chromosomal aberrations in the gametes ultimately decrease both the morphologic quality of embryos and the pregnancy rate. In this study, we investigated whether paternal age affected the euploidy rate. METHODS: This study was performed using the medical records of patients who underwent in vitro fertilization (IVF) procedures with preimplantation genetic screening (PGS) from January 2016 to August 2017 at a single center. Based on their morphological grade, embryos were categorized as good- or poor-quality blastocysts. The effects of paternal age were elucidated by adjusting for maternal age. RESULTS: Among the 571 total blastocysts, 219 euploid blastocysts were analyzed by PGS (38.4%). When the study population was divided into four groups according to both maternal and paternal age, significant differences were only noted between groups that differed by maternal age (group 1 vs. 3, p=0.031; group 2 vs. 4, p=0.027). Further analysis revealed no significant differences in the euploidy rate among the groups according to the morphological grade of the embryos. CONCLUSION: Paternal age did not have a significant impact on euploidy rates when PGS was performed. An additional study with a larger sample size is needed to clarify the effects of advanced paternal age on IVF outcomes.

Beta-carotene prevents the spermatogenic disorders induced by exogenous scrotal hyperthermia through modulations of oxidative stress, apoptosis, and androgen biosynthesis in mice / 대한수의학회지

We investigated whether β-carotene (β-CA) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of β-CA or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at 43℃ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and HIF-1α mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, NF-κB, and TGF-β1 mRNAs), and androgen biosynthesis (serological testosterone concentration and 3β-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by β-CA treatment, but only slightly improved by EA treatment. These findings indicate that β-CA, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.

Recovery of Spermatogenesis Following Cancer Treatment with Cytotoxic Chemotherapy and Radiotherapy

The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

C-Type Natriuretic Peptide/Natriuretic Peptide Receptor 2 Is Involved in Cell Proliferation and Testosterone Production in Mouse Leydig Cells

PURPOSE: This study investigated the role of natriuretic peptide receptor 2 (NPR2) on cell proliferation and testosterone secretion in mouse Leydig cells. MATERIALS AND METHODS: Mouse testis of different postnatal stages was isolated to detect the expression C-type natriuretic peptide (CNP) and its receptor NPR2 by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Leydig cells isolated from mouse testis were cultured and treated with shNPR2 lentiviruses or CNP. And then the cyclic guanosine monophosphate production, testosterone secretion, cell proliferation, cell cycle and cell apoptosis in mouse Leydig cells were analyzed by ELISA, RT-qPCR, Cell Counting Kit-8, and flow cytometry. Moreover, the expression of NPR2, cell cycle, apoptosis proliferation and cell cycle related gene were detected by RT-qPCR and Western blot. RESULTS: Knockdown of NPR2 by RNAi resulted in S phase cell cycle arrest, cell apoptosis, and decreased testosterone secretion in mouse Leydig cells. CONCLUSIONS: Our study provides more evidences to better understand the function of CNP/NPR2 pathway in male reproduction, which may help us to treat male infertility.