María Angeles Montoro Sánchez

Combined loss of p21 waf1/cip1 and p27 kip1 enhances tumorigenesis in mice

The cell cycle inhibitors p21Waf1/Cip1 and p27Kip1 are frequently downregulated in many human cancers, and correlate with a worse prognosis. We show here that combined deficiency in p21 and p27 proteins in mice is linked to more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The most common tumors developed in p21p27 double-null mice were endocrine, with a higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas. The combined absence of p21 and p27 proteins delays the incidence of radiation-induced thymic lymphomas with a higher apoptotic rate, measured by active caspase-3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in mice.

Expression of αv, α4, α5 and β3 integrin subunits, fibronectin and vitronectin in goat peri-implantation

Abstract Integrins are glycoprotein heterodimers located in the cell membranes that stimulate intercellular adhesion and act as extracellular matrix (ECM) protein receptors. Although integrins have been detected in the implantation sites of various species, little is known about their participation in ruminant non-invasive placentation. The objective of this study was the detection of α v , α 4 , α 5 , β 1 and β 3 integrin subunits and of two of their ligands, fibronectin and vitronectin, to determine their participation in the caprine peri-implantation process. On Day 21 post-coitum (pc), endometrial epithelium and trophoblastic cells showed an intense α v and β 3 integrin subunits expression and moderate staining for α 4 and α 5 . On Day 23 pc, integrin expression decreased noticeably and only a weak staining of α 4 and β 3 integrin subunits were observed. No β 1 integrin subunit expression was detected on either of the days studied. Fibronectin (FN) expression in trophectodermic and endometrial epithelium was weak or moderate on the days studied while vitronectin (VN) expression in the same tissues was moderate or strong on Day 21 pc but decreased on Day 23 pc. These results suggest that α v β 3 integrin, α 4 and α 5 subunits, VN and FN are expressed in caprine endometrium and blastocyst and may play a role in the cascade of the implantation process.

DETECTION OF ESTROGEN ALPHA AND PROGESTERONE RECEPTORS AND CELL PROLIFERATION IN THE UTERUS DURING EARLY PREGNANCY IN THE GOAT

The objectives of this study were to investigate in the goat uterus the expression of estrogen-alpha (ER alpha) and progesterone receptors (PR) and their relationship to proliferation indices (Ki-67) during peri-implantation on Days 22 to 30 post coitum (pc). Immunohistochemical methods were used to quantify ER alpha and PR for luminal and deep regions of the endometrium and of the myometrium. On Day 22 pc cell proliferation was only observed in the luminal epithelium. On Day 24 pc, high cell proliferation indices were seen in luminal epithelium and proliferation began in the luminal stroma and glands. There was a positive correlation between Ki-67 and total ER alpha score in the luminal epithelium (r = 0.53, P < 0.01). Levels of PR scores were highly correlated with Ki-67 indices in luminal epithelium (r = 0.74, P < 0.01) and stroma (r = 0.70, P < 0.01). No Ki-67 expression was observed in deep glands, stroma or myometrium on any of the days studied. Results indicate that patterns of ER alpha and PR expression differ markedly, and that there was a high correlation between PR expression and cell proliferation in the caprine uterus during the peri-implantation period.

Immunohistochemical localization of epidermal growth factor, transforming growth factor-α and growth factor-βs in the caprine peri-implantation period

Abstract Control over the action of steroid hormones in the uterus and conceptus during the initial period of gestation appears to be regulated locally by growth factors. This study involved immunohistochemical detection of epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and transforming growth factor-βs (TGF-βs), to determine their role in the caprine peri-implantation period. Epidermal growth factor was expressed in the luminal and glandular endometrial epithelium of goats on all days studied (Days 22 to 30 post coitum), but it was not detected in trophoblastic cells or in other embryonic structures. Between Days 22 and 30 post coitum, TGF-α was detected in the epithelial cells and superficial stroma of the uterus and in the trophoendodermic cells of the embryo. Transforming growth factor-βs expression, observed in the endometrium, embryo and extraembryonic membranes on Day 22 post coitum, decreased by Day 24 post coitum and disappeared in the embryo by Day 30 post coitum, while remaining in the other structures. The presence of these growth factors during the periimplantation period in the goat suggests their participation in proliferation and differentiation phenomena which occur during implantation and embryonic development.

Effects of oestrus induction with progestagens or prostaglandin analogues on ovarian and pituitary function in sheep.

The aim of the current study was to determine possible differences in ovarian and pituitary features explaining lower fertility rates in sheep with oestrus induced with intravaginal progestagens or prostaglandin analogues (group FGA and PGF, n=8 in both) when compared to a control group (group C, n=8). The growth profiles and the mean individual sizes of preovulatory follicles were similar between groups; however, the number of preovulatory follicles per ewe and, consequently, the number of ovulations were higher in groups FGA and PGF (2.3±0.3 and 2.0±0.1, respectively) than in group C (1.4±0.1, P<0.05). However, plasma oestradiol concentrations were similar between groups suggesting a defective function in some preovulatory follicles of groups FGA and PGF. In group FGA, the basal LH levels during the follicular phase were lower (0.21±0.0 ng/mL, P<0.005) than in groups C (0.41±0.1 ng/mL) and PGF (0.55±0.1 ng/mL); the onset of preovulatory discharge being later (21.0±2.3h vs. 12.8±1.5 in C and 14.5±1.5 in PGF; P<0.05 for both). Finally, luteal activity was also found to be affected in group FGA; the rate of progesterone secretion per total luteal tissue was lower (range: 0.46-0.65 ng/mL/cm(2)) than in ewes treated with cloprostenol (2.1-3.3 ng/mL/cm(2)) and control sheep (2.0-3.4 ng/mL/cm(2)).

Fibroblastic growth factor receptor (FGF-R) expression during uterine involution in goat

To investigate the possible participation of fibroblastic growth factors (FGFs) in endometrial involution, 20 multiparous goats, slaughtered on days 0, 1, 4, 10, 16 and 22 postpartum (pp), were used. Samples of different parts of the previous pregnant horns were taken and processed using streptoavidin-biotin-peroxidase complex method to analyse FGF receptor (FGF-R) expression. The percentage of positive cells in luminal epithelium, superficial and deep glands and stroma was evaluated. Epithelial, glandular and stromal cells exhibited FGF-R immunoreactivity. No differences between caruncular and inter-caruncular epithelium were observed and staining was most evident in the superficial glands. The greatest degree of FGF-R expression was seen on days 10 and 16 pp, coinciding with epithelial and stromal cellular regeneration. These results suggest that caprine uterine involution is associated with variations in the expression of FGF-R.

Progestogen treatments for cycle management in a sheep model of assisted conception affect the growth patterns, the expression of luteinizing hormone receptors, and the progesterone secretion of induced corpora lutea

OBJECTIVE To determine, in a sheep model, the effect of a short-term progestative treatment on growth dynamics and functionality of induced corpora lutea. DESIGN Observational, model study. SETTING Public university. PATIENT(S) Sixty adult female sheep. INTERVENTION(S) Synchronization and induction of ovulation with progestogens and prostaglandin analogues; ovarian ultrasonography, blood sampling, and ovariectomy. MAIN OUTCOME MEASURE(S) Determination of pituitary function and morphologic characteristics, expression of luteinizing hormone (LH) receptors, and progesterone secretion of corpora lutea. RESULT(S) The use of progestative pretreatments for assisted conception affect the growth patterns, the expression of LH receptors, and the progesterone secretion of induced corpora lutea. CONCLUSION(S) The current study indicates, in a sheep model, the existence of deleterious effects from progestogens on functionality of induced corpora lutea.

La centralización y el conflicto en las empresas del sector químico español

The goal of this paper is to empirically analyze the effect of centralization on functinal and dysfunctional conflict in organizations. To do this we have used a sample of firms from the spanish chemestry industry. Resuls have allowed to analyze the hierarchy of authority and the participation in taking decisions. Additionally, the dysfunctional and functional nature of the organizational conflict has been studied.

El efecto de la centralización/descentralización de una organización sobre su nivel de conflicto: un análisis teórico

A lo largo de este trabajo se presenta un marco teorico que pretende identificar y estudiar en profundidad la relacion entre dos areas o campos de estudio, el diseno organizativo y el comportamiento organizativo. Para ello, se han seleccionado unicamente dos dimensiones objeto de estudio, una por cada area respectivamente. El articulo presenta una relacion que permite estudiar el efecto de la centralizacion / descentralizacion de una organizacion sobre su nivel de conflicto, tanto funcional como disfuncional