Cumulus extracellular matrix is an important part of oocyte microenvironment in ovarian follicles: its remodeling and proteolytic degradation

The extracellular matrix (ECM) is an essential structure with biological activities. It has been shown that the ECM influences gene expression via cytoskeletal components and the gene expression is dependent upon cell interactions with molecules and hormones. The development of ovarian follicles is a hormone dependent process. The surge in the luteinizing hormone triggers ovulatory changes in oocyte microenvironment. In this review, we discuss how proteolytic cleavage affects formation of cumulus ECM following hormonal stimulation; in particular, how the specific proteasome inhibitor MG132 affects gonadotropin-induced cytoskeletal structure, the organization of cumulus ECM, steroidogenesis, and nuclear maturation. We found that after the inhibition of proteolytic cleavage, gonadotropin-stimulated oocyte–cumulus complexes (OCCs) were without any signs of cumulus expansion; they remained compact with preserved cytoskeletal F-actin-rich transzonal projections through the oocyte investments. Concomitantly, a significant decrease was detected in progesterone secretion and in the expression of gonadotropin-stimulated cumulus expansion–related transcripts, such as HAS2 and TNFAIP6. In agreement, the covalent binding between hyaluronan and the heavy chains of serum-derived the inter-alpha-trypsin inhibitor, essential for the organization of cumulus ECM, was missing

Suicidal ideation in patients with obstructive sleep apnoea and its relationship with disease severity, sleep-related problems and social support

We aimed to assess the prevalence of suicidal ideation and to examine the relationships between obstructive sleep apnoea severity, sleep-related problems, social support and suicidal ideation in obstructive sleep apnoea patients. We included 149 patients (68% male; mean age, 48.99 +/- 9.57 years) with diagnosed obstructive sleep apnoea (Apnoea-Hypopnoea Index > 5) based on full-night polysomnography. The prevalence of suicidal ideation among obstructive sleep apnoea patients was 20.1 per cent. Structural equation modelling showed that suicidal ideation in obstructive sleep apnoea was strongly related to poor sleep quality and high fatigue levels. No relationship between social support and suicidal ideation in obstructive sleep apnoea patients was found

Re‐Thinking the Environment, Cities, and Living Spaces for Public Health Purposes, According with the COVID‐19 Lesson: The LVII Erice Charter

Urban planning is a key tool to promote health in cities. The COVID-19 emergency accelerated several social, environmental, and digital challenges, stressing the importance of some issues regarding housing, urban mobility, green areas, and health service networks, urban health policies, and actions. These issues were the subject of an intensive residential course (the 57th) held in Erice, Sicily, in June 2021 in the “International School of Epidemiology and Preventive Medicine G. D’Alessandro”, and the main findings are described here. Methods. Lectures presented the topics, subsequently developed them, and argued them in parallel practical sessions using the World Café technique, since it is well suited for the interaction of participants and the involvement of groups. Results. The World Café provides new insights into how to improve the livability and health of urban spaces, and a set of strategies and actions were proposed for each topic. Discussion and Conclusions. All attendees agreed on the importance of participation in the planning processes, but also on the need for strong political support to ensure the resources needed and a full integration of health with other local policies. A multidisciplinary approach to developing systemic operational capacities and health literacy is considered pivotal to raising awareness and participation

The psychometric properties of the subscales of the GHQ-28 in a multi-ethnic maternal sample: results from the Born in Bradford cohort

Background: Poor maternal mental health can impact on children’s development and wellbeing; however, there is concern about the comparability of screening instruments administered to women of diverse ethnic origin. Methods: We used confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) to examine the subscale structure of the GHQ-28 in an ethnically diverse community cohort of pregnant women in the UK (N = 5,089). We defined five groups according to ethnicity and language of administration, and also conducted a CFA between four groups of 1,095 women who completed the GHQ-28 both during and after pregnancy. Results: After item reduction, 17 of the 28 items were considered to relate to the same four underlying concepts in each group; however, there was variation in the response to individual items by women of different ethnic origin and this rendered between group comparisons problematic. The EFA revealed that these measurement difficulties might be related to variation in the underlying concepts being measured by the factors. Conclusions: We found little evidence to recommend the use of the GHQ-28 subscales in routine clinical or epidemiological assessment of maternal women in populations of diverse ethnicity

Gene Expression Profiling of Preovulatory Follicle in the Buffalo Cow: Effects of Increased IGF-I Concentration on Periovulatory Events

The preovulatory follicle in response to gonadotropin surge undergoes dramatic biochemical, and morphological changes orchestrated by expression changes in hundreds of genes. Employing well characterized bovine preovulatory follicle model, granulosa cells (GCs) and follicle wall were collected from the preovulatory follicle before, 1, 10 and 22 h post peak LH surge. Microarray analysis performed on GCs revealed that 450 and 111 genes were differentially expressed at 1 and 22 h post peak LH surge, respectively. For validation, qPCR and immunocytochemistry analyses were carried out for some of the differentially expressed genes. Expression analysis of many of these genes showed distinct expression patterns in GCs and the follicle wall. To study molecular functions and genetic networks, microarray data was analyzed using Ingenuity Pathway Analysis which revealed majority of the differentially expressed genes to cluster within processes like steroidogenesis, cell survival and cell differentiation. In the ovarian follicle, IGF-I is established to be an important regulator of the above mentioned molecular functions. Thus, further experiments were conducted to verify the effects of increased intrafollicular IGF-I levels on the expression of genes associated with the above mentioned processes. For this purpose, buffalo cows were administered with exogenous bGH to transiently increase circulating and intrafollicular concentrations of IGF-I. The results indicated that increased intrafollicular concentrations of IGF-I caused changes in expression of genes associated with steroidogenesis (StAR, SRF) and apoptosis (BCL-2, FKHR, PAWR). These results taken together suggest that onset of gonadotropin surge triggers activation of various biological pathways and that the effects of growth factors and peptides on gonadotropin actions could be examined during preovulatory follicle development

Comparison of the effects of sub-hypnotic concentrations of propofol and halothane on the acute ventilatory response to hypoxia.

To compare the effects of sub-anaesthetic concentrations of propofol and halothane on the respiratory control system, we have studied the acute ventilatory response to isocapnic hypoxia (AHVR) in 12 adults with and without three different concentrations of propofol and halothane. Target doses for propofol were 0, 0.05, 0.1 and 0.2 of the effective plasma concentration (EC50 = 8.1 micrograms ml-1). Target doses for halothane were 0, 0.05, 0.1 and 0.2 minimum alveolar concentration (MAC = 0.77%). The doses achieved experimentally were 0.01, 0.06, 0.13 and 0.26 of the EC50 for propofol and 0, 0.05, 0.11 and 0.20 MAC for halothane. During the experiment subjects breathed via a mouthpiece from an end-tidal forcing system. End-tidal PO2 (PE'O2) was held at 13.3 kPa for 5 min, and then at 6.7 kPa for 5 min. End-tidal PCO2 (PE'CO2) was held constant at 0.13-0.27 kPa greater than the subject's natural level throughout. The mean values for AHVR with propofol were: 12.8 (SEM 2.4) litre min-1 (0.01 EC50), 10.0 (1.9) litre min-1 (0.06 EC50), 9.8 (2.3) litre min-1 (0.13 EC50) and 4.9 (1.2) litre min-1 (0.26 EC50). The values for AHVR with halothane were: 11.9 (2.4) litre min-1 (0 MAC), 7.8 (1.6) litre min-1 (0.05 MAC), 5.9 (1.2) litre min-1 (0.11 MAC) and 3.2 (1.6) litre min-1 (0.2 MAC). The decline in AHVR with increasing dose for both drugs was statistically significant (ANOVA, P < 0.001); there was no significant difference between the two drugs with respect to this decline. Normoxic ventilation with propofol declined from 13.2 (1.6) litre min-1 (0.01 EC50) to 8.3 (0.9 litre min-1 (0.26 EC50), and with halothane declined from 13.5 (2.0) litre min-1 (0 MAC) to 11.8 (1.6) litre min-1 (0.2 MAC). This was significant for both drugs (ANOVA, P < 0.001)

Versican G1 Fragment Establishes a Strongly Stabilized Interaction with Hyaluronan-Rich Expanding Matrix during Oocyte Maturation

In the mammalian ovary, the hyaluronan (HA)-rich cumulus extracellular matrix (ECM) organized during the gonadotropin-induced process of oocyte maturation is essential for ovulation of the oocyte-cumulus complex (OCC) and fertilization. Versican is an HA-binding proteoglycan that regulates cell function and ECM assembly. Versican cleavage and function remain to be determined in ovarian follicle. We investigated versican expression in porcine ovarian follicles by real-time (RT)-PCR and western blotting. The aims of the present work were to determine whether 1) versican was produced and cleaved by porcine OCCs during gonadotropin stimulation; 2) these processes were autonomous or required the participation of mural granulosa cells (MGCs); and 3) versican cleavage was involved in the formation or degradation of expanded cumulus ECM. We demonstrate two cleavage products of G1 domain of versican (V1) accumulated in the HA-rich cumulus ECM. One of them, a G1-DPEAAE N-terminal fragment (VG1) of similar to 70 kDa, was generated from V1 during organization of HA in in vivo and in vitro expanded porcine OCCs. Second, the V1-cleaved DPEAAE-positive form of similar to 65 kDa was the only species detected in MGCs. No versican cleavage products were detected in OCCs cultured without follicular fluid. In summary, porcine OCCs are autonomous in producing and cleaving V1; the cleaved fragment of similar to 70 kDa VG1 is specific for formation of the expanded cumulus HA-rich ECM