422 research outputs found
New Insight on the In Vitro Effects of Melatonin in Preserving Human Sperm Quality
Spermatozoa (SPZ) are sensitive to stressful conditions, particularly oxidative stress, which alters their quality; thus, the use of protective molecules as an antioxidant is encouraged. Herein, we used melatonin (MLT) to investigate its in vitro effects on human sperm parameters under conditions of oxidative stress induced by cadmium (Cd). Fifteen human semen samples were divided into control, Cd-treated, MLT-treated, and Cd+MLT-treated groups and analyzed after 30 min, 6 h, and 24 h of exposure. Results showed a time-dependent decrease in SPZ motility, DNA integrity, and increased apoptosis induced by oxidative stress, and these effects were counteracted by MLT co-treatment. Based on these data, we further explored additional parameters just at 24 h. The induced oxidative stress, highlighted by the increased lipid peroxidation, reduced the percentage of SPZ able to undertake acrosome reaction and altered the levels and localization of some protein markers of motility (PREP, RSPH6A), morphology (DAAM1), and acrosome membrane (PTMA, IAM38); all these effects were counteracted by MLT co-treatment. Interestingly, MLT alone was able to ameliorate motility at 30 min of incubation compared to the control, while at 24 h, it prevented the physiological alteration in terms of motility, DNA integrity, and apoptosis. Collectively, the data encourage MLT use as an integrative molecule to ameliorate human gamete quality when compromised by stressful conditions
Differential Expression and Localization of EHBP1L1 during the FirstWave of Rat Spermatogenesis Suggest Its Involvement in Acrosome Biogenesis
The identification and characterization of new proteins involved in spermatogenesis is
fundamental, considering that good-quality gametes are basic in ensuring proper reproduction. Here,
we further analyzed the temporal and spatial localization during the first spermatogenic wave of rat
testis of EHBP1L1, which is involved in vesicular trafficking due to the CH and bMERB domains,
which bind to actin and Rab8/10, respectively. Western blot and immunofluorescence analyses
showed that EHBP1L1 protein expression started at 21 days post-partum (dpp) concomitantly
with the appearance of primary spermatocytes (I SPC). In subsequent stages, EHBP1L1 specifically
localized together with actin in the perinuclear cytoplasm close to the acrosomal and Golgian
regions of spermatids (SPT) during the different phases of acrosome biogenesis (AB). Moreover,
it was completely absent in elongated SPT and in mature spermatozoa, suggesting that its role
was completed in previous stages. The combined data, also supported by our previous report
demonstrating that EHBP1L1 mRNA was expressed by primary (I) and secondary (II) SPC, lead us to
hypothesize its specific role during AB. Although these results are suggestive, further studies are
needed to better clarify the underlying molecular mechanisms of AB, with the aim to use EHBP1L1
as a potential new marker for spermatogenesis
Male Reproduction: Regulation, Differentiation and Epigenetics
The production of good-quality spermatozoa (SPZ) is one of the most intricate and far from being completely understood developmental processes during postnatal life [...
Electrical Loads and Power Systems for the DEMO Nuclear Fusion Project
EU-DEMO is a European project, having the ambitious goal to be the first demonstrative
power plant based on nuclear fusion. The electrical power that is expected to be produced is in the
order of 700–800 MW, to be delivered via a connection to the European High Voltage electrical grid.
The initiation and control of fusion processes, besides the problems related to the nuclear physics,
need very complex electrical systems. Moreover, also the conversion of the output power is not
trivial, especially because of the inherent discontinuity in the EU-DEMO operations. The present
article concerns preliminary studies for the feasibility and realization of the nuclear fusion power
plant EU-DEMO, with a special focus on the power electrical systems. In particular, the first stage of
the study deals with the survey and analysis of the electrical loads, starting from the steady-state
loads. Their impact is so relevant that could jeopardy the efficiency and the convenience of the plant
itself. Afterwards, the loads are inserted into a preliminary internal distribution grid, sizing the main
electrical components to carry out the power flow analysis, which is based on simulation models
implemented in the DIgSILENT PowerFactory software
Preliminary Investigation on the Ameliorative Role Exerted by D-Aspartic Acid in Counteracting Ethane Dimethane Sulfonate (EDS) Toxicity in the Rat Testis.
Herein is reported the first evidence of the protective role of D-aspartic acid (D-Asp) in
preventing the toxic effect exerted by the alkylating agent ethane dimethane sulfonate (EDS) in the
rat testis. We confirmed that EDS treatment specifically destroyed Leydig cells (LC), resulting in the
drastic decrease of the serum testosterone level and producing morphological changes in the germinal
tubules, i.e., altered organization of the epithelium, loss of cell contacts and the consequent
presence of empty spaces between them, and a reduce number of spermatozoa. Moreover, an increase
of TUNEL-positive germ cells, other than alteration in the protein level and localization of
two LC “markers”, StAR and PREP, were observed. Interestingly, results obtained from rats pretreated
with D-Asp for 15 days before EDS-injection showed that all the considered parameters
were quite normal. To explore the probable mechanism(s) involved in the protection exerted by DAsp,
we considered the increased oxidative stress induced by EDS and the D-Asp antioxidant effects.
Thiobarbiturc acid-reactive species (TBARS) levels increased following EDS-injection, while
no change was observed in the D-Asp + EDS treated rats. Our results showed that D-Asp may be
used as a strategy to mitigate the toxic effects exerted by environmental pollutants, as endocrine
disrupters, in order to preserve the reproductive function
Evidence of melatonin ameliorative effects on the blood-testis barrier and sperm quality alterations induced by cadmium in the rat testis.
Herein, we further document the protective action of melatonin (MLT) in mitigating cadmium (Cd)-induced toxicity on male adult rat testis. Cd treatment provoked testicular injury, that was documented by histological and biomolecular alterations, i.e., decrease of serum and testicular testosterone concentration and modified sperm parameters. Mainly, both the cytoarchitecture of the blood-testis barrier (BTB) and germ cell morphology were perturbed, as highlighted by impairment in structural (OCN, VANGL, Cx43) and regulative (Src and FAK) protein levels and/or activation. The study focused on the involvement of the autophagy pathway, that was enhanced especially in the Sertoli cells, probably in response to the disorganization of the BTB. Results obtained with the MLT co-treatment demonstrated that its administration decreased the level of oxidative damage caused by Cd, with reversal of all the observed changes. Moreover, the beneficial effects of MLT alone were evidenced by an increase of sperm quality, in term of motility and DNA integrity. The combined results, obtained in rat, strongly encourage to consider a role for MLT in improving also human testicular health, not only in men exposed to Cd, but also in those having fertility disorders, to ameliorate sperm quality and, consequently, reproductive success
Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity is Counteracted by Melatonin in the Rat Testis.
Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells, provoked testicular injury, as documented by biomolecular and histo-logical alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration effects in mitigating Cd-induced toxicity on adult rat testis, as demon-strated by the reduction of oxidative stress and apoptosis, with reversal of the observed histolog-ical changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, involved in the germ cells differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT at-tenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity, acting on DAAM1 and PREP expression, encouraging further studies to prove its effec-tiveness in human health
Environmental microplastics (EMPs) exposure alter the differentiation potential of mesenchymal stromal cells
Humans are exposed to environmental microplastic (MPs) that can be frequent in surrounding environment. The mesenchymal stromal cells are a heterogeneous population, which contain fibroblasts and stromal cells, progenitor cells and stem cells. They are part of the stromal component of most tissue and organs in our organisms. Any injury to their functions may impair tissue renewal and homeostasis. We evaluated the effects of different size MPs that could be present in water bottles on human bone marrow mesenchymal stromal cells (BMMSCs) and adipose mesenchymal stromal cells (AMSCs). MPs of polyethylene terephthalate (MPs-PET) (<1 μm and <2.6 μm) were tested in this study. PET treatments induced a reduction in proliferating cells (around 30%) associated either with the onset of senescence or increase in apoptosis. The AMSCs and BMMSCs exposed to PET showed an alteration of differentiation potential. AMSCs remained in an early stage of adipocyte differentiation as shown by high levels of mRNA for Peroxisome Proliferator Activated Receptor Gamma (PPARG) (7.51 vs 1.00) and reduction in Lipoprotein Lipase (LPL) mRNA levels (0.5 vs 1.0). A loss of differentiation capacity was also observed for the osteocyte phenotype in BMMSCs. In particular, we observed a reduction in Bone Gamma-Carboxy glutamate Protein (BGLAP) (0.4 for PET1 and 0.6 for PET2.6 vs 0.1 CTRL) and reduction in Osteopontin (SPP1) (0.3 for PET 1 and 0.64 for PET 2.6 vs 0.1 CTRL). This pioneering mesenchymal cell response study demonstrated that environmental microplastic could be bioavailable for cell uptake and may further lead to irreversible diseases
Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: A novel class of irreversible inhibitors of histone demethylase KDM1A
Measurement of the very rare decay
The decay K+→π+νν¯
, with a very precisely predicted branching ratio of less than 10−10
,
is among the best processes to reveal indirect effects of new physics.
The NA62 experiment at CERN SPS is designed to study the K+→π+νν¯
decay and to measure its branching ratio using a decay-in-flight technique.
NA62 took data in 2016, 2017 and 2018, reaching the sensitivity of the Standard Model
for the K+→π+νν¯
decay by the analysis of the 2016 and 2017 data,
and providing the most precise measurement of the branching ratio to date
by the analysis of the 2018 data.
This measurement is also used to set limits on BR(K+→π+X
), where X
is a scalar
or pseudo-scalar particle.
The final result of the BR(K+→π+νν¯
) measurement and its interpretation in terms
of the K+→π+X
decay from the analysis of the full 2016-2018 data set is presented, and future plans and prospects are reviewed
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