Epigenetic clocks and female fertility timeline: A new approach to an old issue?

Worldwide increase in life expectancy has boosted research on aging. Overcoming the concept of chronological age, higher attention has been addressed to biological age, which reflects a person’s real health state, and which may be the resulting combination of both intrinsic and environmental factors. As epigenetics may exert a pivotal role in the biological aging, epigenetic clocks were developed. They are based on mathematical models aimed at identifying DNA methylation patterns that can define the biological age and that can be adopted for different clinical scopes (i.e., estimation of the risks of developing age-related disorders or predicting lifespan). Recently, epigenetic clocks have gained a peculiar attention in the fertility research field, in particular in the female counterpart. The insight into the possible relations between epigenetic aging and women’s infertility might glean additional information about certain conditions that are still not completely understood. Moreover, they could disclose significant implications for health promotion programs in infertile women. Of relevance here is that the impact of biological age and epigenetics may not be limited to fertility status but could translate into pregnancy issues. Indeed, epigenetic alterations of the mother may transfer into the offspring, and pregnancy itself as well as related complications could contribute to epigenetic modifications in both the mother and newborn. However, even if the growing interest has culminated in the conspicuous production of studies on these topics, a global overview and the availability of validated instruments for diagnosis is still missing. The present narrative review aims to explore the possible bonds between epigenetic aging and fertility timeline. In the “infertility” section, we will discuss the advances on epigenetic clocks focusing on the different tissues examined (endometrium, peripheral blood, ovaries). In the “pregnancy” section, we will discuss the results obtained from placenta, umbilical cord and peripheral blood. The possible role of epigenetic aging on infertility mechanisms and pregnancy outcomes represents a question that may configure epigenetic clock as a bond between two apparently opposite worlds: infertility and pregnancy

Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies

According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/β-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis

ART and the forgotten siblings: a call for research

A broader definition of infertility is the incapacity to have the intended number of children. However, most literature on ART exclusively focuses on live birth as an outcome, rather than on the capacity to fully realize the reproductive wishes of the couples. This issue has probably received scant attention because the total fertility rate is below replacement levels in affluent countries, and one may simplistically assume that only a minority of couples may be interested in more than one child. This assumption, however, is unproven and presumably erroneous. Unfortunately, evidence on the rate of return in couples who conceived their first child with ART is scant and information on the intended number of children in infertile couples is lacking. In general, we plea for more research on this subject. The documentation of an intended number of children above two and a high return rate in infertile couples may lead to changes in clinical practice, such as the storage of oocytes or embryos prior to initiating embryo transfers. This could improve the chance of conceiving the second child when the couple comes back some years later. In addition, the identification of the determinants for non-return as well as those explaining the gap between the intended and the realized number of children may reveal specific barriers and possibly how to tackle them. However, at present, available evidence is insufficient to advocate any intervention. Thorough research is warranted

Plaque quantification by coronary computed tomography angiography using intravascular ultrasound as a reference standard: a comparison between standard and last generation computed tomography scanners

AIMS: The emerging role of coronary computed tomography angiography (CCTA) as a non-invasive tool for atherosclerosis evaluation is supported by data reporting a good correlation between CCTA and intravascular ultrasound (IVUS) for plaque volume quantification. Aim of the present study was to evaluate whether a last generation CT-scanner may improve coronary plaque volume assessment using IVUS as standard-of-reference. METHODS AND RESULTS: From a registry of 1915 consecutive, all-comers, patients who underwent a clinically indicated IVUS evaluation we enrolled 59 patients who underwent CCTA with a 64-slice CT (Group 1) and 59 patients who underwent CCTA with whole-heart coverage CT scanner (Group 2). Patients who underwent CCTA with unfavourable heart rhythm were not excluded from the analysis. Image quality (4-point Likert scale) focused on plaque analysis was evaluated. Plaque volume quantification by CCTA was compared to IVUS. No difference in clinical characteristics was found between Group 1 and Group 2. Plaque volume quantification by CCTA was considered not feasible in 11 plaques of Group 1 and in 4 plaques of Group 2 (P = 0.09). Higher correlation for plaque volume quantification by CCTA vs. IVUS was demonstrated in Group 2 when compared with Group 1 (r = 0.9888 vs. 0.9499; P < 0.0001). The Bland-Altman analysis showed plaque volume overestimation by CCTA of 11.9 mm3 in Group 1 and 4 mm2 in Group 2 (P < 0.001). Effective radiation dose of CCTA was significantly lower in Group 2 vs. Group 1 (2.7 ± 0.9 vs. 8.1 ± 3.6 mSv, respectively; P < 0.001). CONCLUSIONS: CCTA using a new scanner generation showed to be an accurate non-invasive tool to assess and quantify coronary plaque volume