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Biomarkers of ovarian ageing
Get PDFThe ovary is the main regulator of female fertility, and its biologic clock is set to ensure reproductive success during a definite life stage. According to the evolutionary concept that organisms maximize fitness by promoting production of progeny, allocation of resources between reproductive and somatic functions is finely regulated during life. Thus, it has been speculated that the premature ageing of the ovary when compared with somatic organs might result from increased energy demand for maintenance and repair processes in the soma compartment during ageing.
According to the human biologic clock, the gradual loss of female fertility becomes more dramatic in the late 30s with a steep decrease beginning after age 35, ending in menopause at mean age of 51 years. This would preserve women from the physical stress of pregnancy in advanced age and maximize the length of time they can bear children. As a result, increasing postponement of the first pregnancy represents a crucial factor in the widespread of subfertility in industrialized societies. Given the intrapopulation variability of the reproductive life span, it is generally accepted that coping with this issue requires a careful reproductive counselling based on accurate predictive markers.
Ovarian functional decline with ageing has been so far extensively characterized in terms of gradual depletion of ovarian follicles and reduced ability to produce oocytes competent for fertilization and further development. The analysis of the
molecular and cellular aspects of follicle ageing would require careful consideration.
In fact, oocytes and granulosa cells of primordial follicles might remain in ‘resting’ phase for a long time, thus behaving as post-mitotic cells which can be required to start growing after 10–50 years. Furthermore, both primordial and growing follicles become exposed to environmental factors related to the ageing of the ovarian somatic compartment, and finally, the development of a competent oocyte intimately depends on the crosstalk between all compartments in the ovary.
For decades, research on reproductive ageing has been focusing on the so-called quantitative aspect of ovarian ageing, which has led to mathematical models predicting follicle loss on the basis of chronologic age without taking into account
biologic markers. When the concept of oocyte ageing as the main determinant of fertility decline has become clear, researchers have begun to expand investigations into the whole ovarian microenvironment in search of age-related changes with potential effects on follicle and oocyte competence.
Although it is generally accepted that ageing is a result of both inborn and environmental factors, most of the numerous theories of ageing share the concept that age-associated malfunction results from physiological accumulation of irreparable damage to biomolecules as an unavoidable side effect of normal metabolism and underline the importance of the capability of defensive repair.
More than a decade after the free radical theory of ovarian ageing first proposed by Tarin, biological and clinical research has provided numerous evidence that increased reactive oxygen species (ROS), which are among the most important physiological inducers of cellular injury associated with ageing, is a main determinant to follicle ageing. ROS generated by mitochondrial dysfunction is considered the main cause for telomere shortening, chromosomal segregation disorders, maturation and fertilization failures or oocyte/embryo fragmentation. Looking for ROS aetiology and widespread, a relevant role has been ascribed to advanced glycation end products (AGEs) , factors that may hamper ovarian stroma vessels, follicular growth, assembly of an efficient system of antioxidant enzymatic defence as well as development of an efficient perifollicular vascularization. Further evidence for ROS in the ovarian follicle was obtained by research on stress signalling pathways in aged granulosa and cumulus cells. Enzymatic activity and protein level of superoxide dismutase (SOD), the enzyme that reacts with superoxide anion radicals to form oxygen and H2 O2 , were found to decrease with age, and lower levels of SOD activity are associated with unsuccessful IVF outcomes. Nevertheless, there are poor evidences for possible benefits from antioxidant treatments in humans, suggesting that further actors are involved in modulating stress adaptive response in the ovary during agein
Gene expression in cumulus cells and oocyte quality
Get PDFInfertility is a worldwide growing issue, and female factors account for about 30 % of the total cases of infertility. The majority of couples affected by infertility undergo in vitro fertilization (IVF) protocols following women hormonal hyperstimulation cycles to obtain mature oocytes to fertilize in vitro. Nowadays, the oocyte/embryo quality is mainly assessed by morphokinetic parameters even if these approaches have low objective prediction value. The rate of live newborns after IVF is relatively low, ranging from about 30 % in younger women to 10 % in the older ones. Aging, in fact, is a well-known critical factor for the success of IVF protocols. As a consequence, a primary goal in older women is to increase the pregnancy rate, with a crucial point represented by the selection of the oocytes to fertilize in vitro and transfer in women.
In this view, transcriptomic information about granulosa cells (GCs) might shed light on the oocyte viability, thereby providing a non-invasive method of oocyte/embryo selection.
The nutritional support and trafficking of macromolecules that this system allows may be particularly important for oocytes due to the avascular nature of the granulose layer. The signaling between GCs and oocyte via cytoplasmic processes penetrating the zona pellucid and forming gap junctions at the oocyte surface is a key means of disseminating local and endocrine signals to the oocyte. In fact, GCs functionality is a key determinant of the oocyte quality and competence, since GCs are the somatic cells strictly connected to the growing oocyte by a bidirectional communication ensuring the environment for its correct development. It is clear that the role of the oocyte extends far beyond its functions in the transmission of genetic information and supply of raw materials to the early embryo. It also has a critical part to play in mammalian follicular control and the regulation of oogenesis, ovulation rate, and fecundity.
This chapter is aimed to explore the GCs gene activity in physiological and pathological conditions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Pregnancy outcome in women with uterine anomalies
No full textAims: To review the impact of female genital malformations as well as their different types on pregnancy outcome.Methods: Pertinent studies were identified through a computer Medline, Embase and Cochrane Library search. Uterine defects were grouped into five classes, according to the new ESHRE/ESGE Classification of Female Genital Malformations. Only data on untreated congenital uterine anomalies, apart for metroplasty in bicornuate uterus, were taken into account in accordance to the objective of the issue.Clinical implications: Those uterine malformations that cannot be surgically treated (Hemi-uterus and Bicorporeal uterus with double cervix AFS Unicornuate and Didelphys uteri) are associated with poor reproductive performances, increased abortion rates and lower live birth rates, eventhough a successful pregnancy is possible. On the opposite, septate uterus, hypoplastic uterus (AFS “T-shaped”) and partial unification defects (AFS bicornuate uterus) are associated to the worst reproductive outcomes when untreated and to the higher reproductive performances after surgery.Open issue: The hypoplastic uterus (T-shaped/Uterus Infantilis) is an old/new congenital pathology to be taken into account, both for its increasing incidence and damage of reproductive outcome and for the promising results of hysteroscopic surgery in those patients.Further researches concerning new clinical and diagnostic parameters are also advisable, in order to individuate those subpopulations of patients with uterine congenital anomalies, i.e. women with septate uterus, that will benefit of surgical procedure.Finally, focusing again on septate uterus, further controlled trials are needed in order to get to a definite conclusion on the issue of the length of the septum into the uterine cavity and the impairment of pregnancy. © Springer-Verlag London 2015
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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