Predicting risk of endometrial failure: a biomarker signature that identifies a novel disruption independent of endometrial timing in patients undergoing hormonal replacement cycles.

OBJECTIVE: To propose a new gene expression signature that identifies endometrial disruptions independent of endometrial luteal phase timing and predicts if patients are at risk of endometrial failure. DESIGN: Multicentric, prospective study. SETTING: Reproductive medicine research department in a public hospital affiliated with private fertility clinics and a reproductive genetics laboratory. PATIENTS: Caucasian women (n = 281; 39.4 ± 4.8 years old with a body mass index of 22.9 ± 3.5 kg/m2) undergoing hormone replacement therapy between July 2018 and July 2021. Endometrial samples from 217 patients met RNA quality criteria for signature discovery and analysis. INTERVENTION(S): Endometrial biopsies collected in the mid-secretory phase. MAIN OUTCOME MEASURE(S): Endometrial luteal phase timing-corrected expression of 404 genes and reproductive outcomes of the first single embryo transfer (SET) after biopsy collection to identify prognostic biomarkers of endometrial failure. RESULTS: Removal of endometrial timing variation from gene expression data allowed patients to be stratified into poor (n = 137) or good (n = 49) endometrial prognosis groups on the basis of their clinical and transcriptomic profiles. Significant differences were found between endometrial prognosis groups in terms of reproductive rates: pregnancy (44.6% vs. 79.6%), live birth (25.6% vs. 77.6%), clinical miscarriage (22.2% vs. 2.6%), and biochemical miscarriage (20.4% vs. 0%). The relative risk of endometrial failure for patients predicted as a poor endometrial prognosis was 3.3 times higher than those with a good prognosis. The differences in gene expression between both profiles were proposed as a biomarker, coined the endometrial failure risk (EFR) signature. Poor prognosis profiles were characterized by 59 upregulated and 63 downregulated genes mainly involved in regulation (17.0%), metabolism (8.4%), immune response, and inflammation (7.8%). This EFR signature had a median accuracy of 0.92 (min = 0.88, max = 0.94), median sensitivity of 0.96 (min = 0.91, max = 0.98), and median specificity of 0.84 (min = 0.77, max = 0.88), positioning itself as a promising biomarker for endometrial evaluation. CONCLUSION(S): The EFR signature revealed a novel endometrial disruption, independent of endometrial luteal phase timing, present in 73.7% of patients. This EFR signature stratified patients into 2 significantly distinct and clinically relevant prognosis profiles providing opportunities for personalized therapy. Nevertheless, further validations are needed before implementing this gene signature as an artificial intelligence (AI)-based tool to reduce the risk of patients experiencing endometrial failure.

Genetic stability of Solanum tuberosum L. CV. Désirée plantlets obtained from embryogenic cell suspension cultures

Se analizó la estabilidad genética de plántulas de Solanum tuberosum L. cv. Désirée obtenidas a partir del cultivo de células embriogénicas en suspensión, las que fueron inducidas a partir de callos mixoploides con abundantes células binucleadas. Las plantas regeneradas a partir de estos tejidos presentaron un número euploide de cromosomas (2n=4x=48). Este resultado indica que en este sistema las células euploides fueron seleccionadas para seguir el proceso de embryogenesis somática y regeneración de plantas. La estabilidad genotípica de las plantas regeneradas fue evaluada mediante marcadores RAPD. Los resultados indican que las nuevas poblaciones de plantas son altamente homogéneas.

Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer.

Success in breast cancer treatment depends greatly upon early detection, and in the employment of prognostic markers able to anticipate the evolution of the disease, allowing a more rational management of the patient. A fundamental cause of cancer is the alteration of the genetic material, which may modify the expression of proteins that play key roles in cell cycle progression. The aim of this study was to analyze the expression of cyclins D1, E, and B1 and of the CDKIs p16 and p21 in a population of uniformly treated patients with stage I or II breast tumors (n=56) compared with patients with benign breast pathology (n=23). Malignant breast tumors showed higher cyclin E and lower p21 expression than benign breast pathology (NS), determined by immunohistochemistry (IHC). In breast cancer patients, overexpression of cyclins D1 and E was associated with the presence of ER and stage respectively independently of other prognostic variables (multivariate analysis). Kaplan-Meier curves demonstrated that only overexpression of cyclin E was associated with a longer recurrence-free survival. Cox analysis showed that neither cyclins nor CDKIs were independent prognostic markers. We demonstrated that several regulators of cell cycle progression were altered in a large number of breast tumor cases, however, these abnormalities were not indicators of a worse outcome in breast cancer patients of stages I and II.

Estudios anatomicos y morfologicos de la iniciacion de embriones somaticos obtenidos a partir de apices meristematicos de Musa sp / Anatomic and morphological studies on the initiation of somatic embryos obtained from meristematic apexes of Musa sp

El origen de embriones somáticos obtenidos de ápices meristemáticos del clon de Musa (AAA) 'Gran enano', fue analizado mediante estudios histológicos y morfológicos durante las diferentes fases de desarrollo del proceso. La investigación reveló que los embriones somáticos se originaron directamente de células del parénquima perivascular de las hojas. Secciones histológicas de los embriones globulares mostraron una disposición radial de las células y la presencia de una epidermis que rodea completamente al embrión. Con la adición de citocinina (Z o BA), algunos embriones permanecieron en estado globular, con ligeros signos de agrandamiento sin un posterior desarrollo de la invaginación. Otros lograron alcanzar el estado de embrión globular con invaginación; otros el estado alargado, con una clara diferenciación entre el extremo apical y basal y con tejidos fotosintéticamente activos, pero no se logró la regeneración de plantas completas. Tratamientos adicionales, como es el someter a los embriones a un "shock osmótico" o la adición de GA3, fueron también probados sin éxito. Al presente, no tenemos una explicación para la no regeneración de las plantas, por lo tanto sugerimos que se deben realizar experimentos adicionales, como lo son estudios histológicos y bioquímicos en estados tempranos, intermedios y tardíos de la embriogénesis somática, para tratar de entender en que momento y porque, son interrumpidos los procesos fisiológicos normales del desarrollo del embrión.