Higher Damage Levels Research Articles

Torpid 13-lined ground squirrel liver mitochondria resist anoxia-reoxygenation despite high levels of protein damage.

Hibernation confers resistance to ischemia-reperfusion injury in tissue, but the underlying mechanisms remain unclear. Suppression of mitochondrial respiration during torpor may contribute to this tolerance. To explore this concept, we subjected isolated liver mitochondria from torpid, interbout euthermic (IBE) and summer 13-lined ground squirrels (Ictidomys tridecemlineatus) to 5 min of anoxia, followed by reoxygenation (A/R). We also included rat liver mitochondria as a non-hibernating comparison group. Maximum respiration rates of mitochondria from torpid ground squirrels were not affected by A/R, but in IBE and summer, these rates decreased by 50% following A/R and in rats they decreased by 80%. Comparing net ROS production rates among groups, revealed seasonal differences; mitochondria from IBE and torpor produced 75% less ROS than summer ground squirrels and rats. Measurements of oxidative damage to these mitochondria, both freshly isolated, as well as pre- and post-A/R, demonstrated elevated damage to protein, but not lipids, in all groups. Hibernation likely generates oxidative stress, as freshly isolated mitochondria had greater protein damage in torpor and IBE than in summer and rats. When comparing markers of damage pre- and post-A/R, we found that when RET was active, rat macromolecules were more damaged than when RET is inhibited, but in TLGS markers of damage were similar. This result suggests that suppression of RET during hibernation, both in torpor and IBE, lessens oxidative stress produced during arousal. Taken together our study suggests that ischemia-reperfusion tolerance at the mitochondrial level is associated with metabolically suppressed oxidative phosphorylation during hibernation.

40,000 years of technological continuity and change at Matja Kuru 2, Timor-Leste

Timor-Leste is known for long-term continuity in lithic manufacturing techniques that span at least the last 44,000 years. Here we confirm this pattern of long-term continuity in stone tool manufacture at the site of Matja Kuru 2, located on Timor-Leste close to the freshwater Lake Ira Lalaro. The lithic assemblage is characterised by high reduction intensity and frequent use of bipolar, ‘core-on-flake’, discoidal and multiplatform core reduction to produce small flakes while high levels of retouch, heat damage and breakage. While continuity is an important feature of the assemblage, we also document important changes in technology, raw material selection and recycling/extension strategies over time. We posit that the long periods of absence at MK2 may coincide with drier phases when Ira Lalaro likely dried and that more extensive use of the cave occurs during wet phases with attendant lake high conditions. The lithic assemblage indicates increased mobility and individual provisioning in the transitions between these phases of site use and abandonment. The Matja Kuru 2 lithic assemblage also reveals the earliest known evidence yet found for obsidian and possible inter-island transport in Wallacea.

ENVIRONMENTAL AND SOCIAL INJUSTICE: IMPACT AND SUSTAINABILITY OF SMALL SCALE TIN MINING UNDER INDONESIA’S NEW MINERAL AND COAL REGULATION

The transformation of mining law policy in Law No. 3 of 2020 concerning Minerals and Coal has broad implications for mining law, including illegal tin mining. The high dependence of the tin extractive economy in Bangka Belitung has changed the landscape of this archipelago province as an area with a high level of natural damage and social disasters. The ability of governments through regulatory instruments to tackle illegal mining is an important ideal goal. This research was conducted using socio-legal methods, to produce a comprehensive analysis related to the environmental and social impacts of illegal tin mining after the renewal of the mineral and coal law. This study found that the transition of mining authority from the central government to the regional government directly has an impact on the proliferation of illegal mining activities. Substantive changes in the mineral and coal law have not provided a strategic solution because the tug-of-war over authority ends with the continued delegation of authority to grant community mining permits to local governments. Meanwhile, the unpreparedness of local governments has resulted in the continued marginalization of mining communities and has an impact on widespread environmental damage. The lack of fair decision-making processes for people mining licences is indicative of an immature tin mining management in Bangka Belitung. The purpose of this study is to provide a comprehensive overview of the implications of the latest mineral and coal policies on illegal tin mining activities, as a reference and consideration in strategic policy making to create an ideal and sustainable tin mining ecosystem.

Evaluation of the impact of nanomodification on Self-Healing behavior of asphalt binders

Nanomaterials, due to their higher surface area, smaller particle size, and unique chemical characteristics, might be a potential additive to self-heal microcracks in asphalt pavement and extend pavement life. The goal of this study is to examine the self-healing potential of asphalt binder modified with nanosilica, nanoalumina, and nanoclay at three different dosages. First, factors affecting self-healing behavior (i.e., blending techniques, rest period, and damage level) were investigated following Performance grade, Surface Free Energy, Storage stability, and Fourier Transform Infrared Spectroscopy tests. 1% nanosilica exhibited the highest self-healing potential, while 3% nanoalumina also performed well at higher damage levels.

2023 Elections in Turkey within Global Context: Right Wing Populism in the Era of Global Shift

ABSTRACT Many observers predicted that the catastrophic earthquake of February 2023 and huge and unprecedent problems of high inflation and cost of living crisis would end Erdogan era and his credibility in Turkey. However, despite all ongoing deep problems, Erdogan and his AKP government, after more than 20 years in power, still managed to win the 2023 elections in the second round. It seems none of the serious economic and political problems were enough to get the majority of votes away from the governing party, AKP. Even in the cities where the earthquake costed high level of damage, AKP and Erdogan got significantly high votes, despite rampant corruption and economic mismanagement. The AKP government has not been punished either economically or politically. On the contrary, one of the most striking consequences of this election is that Turkey now has the most right-wing parliament in its recent modern history if we include the right-wing opposition parties in the composition.

RB loss sensitizes cells to replication-associated DNA damage after PARP inhibition by trapping.

The retinoblastoma tumor suppressor protein (RB) interacts physically and functionally with a number of epigenetic modifying enzymes to control transcriptional regulation, respond to replication stress, promote DNA damage response and repair, and regulate genome stability. To better understand how disruption of RB function impacts epigenetic regulation of genome stability and determine whether such changes represent exploitable weaknesses of RB-deficient cancer cells, we performed an imaging-based screen to identify epigenetic inhibitors that promote DNA damage and compromise the viability of RB-deficient cells. We found that loss of RB alone leads to high levels of replication-dependent poly-ADP ribosylation (PARylation) and that preventing PARylation by trapping PARP enzymes on chromatin enables RB-deficient cells to progress to mitosis with unresolved replication stress. These defects contribute to high levels of DNA damage and compromised cell viability. We demonstrate this sensitivity is conserved across a panel of drugs that target both PARP1 and PARP2 and can be suppressed by reexpression of the RB protein. Together, these data indicate that drugs that target PARP1 and PARP2 may be clinically relevant for RB-deficient cancers.

A rapid numerical-based vulnerability assessment method for masonry buildings subject to flood

Buildings exposed to high-intensity flood actions can experience severe damage and collapse. Rapid procedures can significantly aid in identifying the most vulnerable buildings within large flood-risk areas, enabling the implementation of retrofitting and mitigation measures. Motivated by this need, in this work we propose a simplified vulnerability assessment method that employs a mechanics-based approach. This strategy exclusively addresses the structural damage and is based on assigning a Vulnerability Index to each building. Then, considering some hazard intensity indicators, the method gives the most probable damage level. The main novelty of the proposed method lies in its calibration, which is performed on the results of a high number of numerical analyses. Results show a good agreement between the proposed simplified method and the numerical simulations, particularly in estimating high or low damage levels. Finally, the method is applied to a case study regarding the municipality of Crotone, in southern Italy.

Development of [225Ac]Ac-DOTA-C595 as radioimmunotherapy of pancreatic cancer: in vitro evaluation, dosimetric assessment and detector calibration

BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy which may benefit from radioimmunotherapy. Previously, [177Lu]Lu-DOTA-C595 has been developed as a beta-emitting radioimmunoconjugate to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on PDAC. However, the therapeutic effect may be enhanced by using an alpha-emitting radionuclide such as Actinium-225 (Ac-225). The short range and high linear energy transfer of alpha particles provides dense cellular damage and can overcome typical barriers related to PDAC treatment such as hypoxia. Despite the added cytotoxicity of alpha-emitters, their clinical implementation can be complicated by their complex decay chains, recoil energy and short-range impeding radiation detection. In this study, we developed and evaluated [225Ac]Ac-DOTA-C595 as an alpha-emitting radioimmunotherapy against PDAC using a series of in vitro experiments and conducted a preliminary dosimetric assessment and cross-calibration of detectors for the clinical implementation of Ac-225.ResultsCell binding and internalisation of [225Ac]Ac-DOTA-C595 was rapid and greatest in cells with strong MUC1-CE expression. Over 99% of PDAC cells had positive yH2AX expression within 1 h of [225Ac]Ac-DOTA-C595 exposure, suggesting a high level of DNA damage. Clonogenic assays further illustrated the cytotoxicity of [225Ac]Ac-DOTA-C595 in a concentration-dependent manner. At low concentrations of [225Ac]Ac-DOTA-C595, cells with strong MUC1-CE expression had lower cell survival than cells with weak MUC1-CE expression, yet survival was similar between cell lines at high concentrations irrespective of MUC1-CE expression. A dosimetric assessment was performed to estimate the dose-rate of 1 kBq of [225Ac]Ac-DOTA-C595 with consideration to alpha particles. Total absorption of 1 kBq of Ac-225 was estimated to provide a dose rate of 17.5 mGy/h, confirmed via both detector measurements and calculations.Conclusion[225Ac]Ac-DOTA-C595 was shown to target and induce a therapeutic effect in MUC1-CE expressing PDAC cells.

Invasive Whitefly (Hemiptera: Aleyrodidae) Complex and Diversity in Coconut Landscapes in Tamil Nadu

Abstract Coconut, Cocos nucifera L., in Tamil Nadu, India, was invaded by four whitefly (Hemiptera: Aleyrodidae) species between 2016 and 2019, increasing the total to six, along with Aleurodicus dispersus Russell and Aleurocanthus arecae David and Manjunatha. We examined the complexity and diversity of whiteflies in coconut across different agroclimatic zones of Tamil Nadu and found high and low damage levels by whiteflies at Veppankulam (70.4%) and Rameswaram (11.0%), respectively. The rugose spiraling whitefly, Aleurodicus rugioperculatus Martin, was the most dominant species but was effectively managed by the parasitoids Encarsia guadeloupae Viggiani and E. dispersa Polaszek, with the highest rate parasitism of 83.8% at Aliyar Nagar and the lowest (2.9%) in the Kanchipuram district. Aleurodicus rugioperculatus and Bondar’s nesting whitefly, Paraleyrodes bondari Peracchi, have spread throughout Tamil Nadu. The population of A. rugioperculaus was high at Veppankulam and that of P. bondari was higher at Dharmapuri (28.6 and 31.1 adults/leaflet, respectively). All five invasive whitefly species in coconut were found only in 7 of 34 locations—Coimbatore, Sirumugai, Salem, Dharmapuri, Krishnagiri, Vellore, and Erode. Paraleyrodes minei Iaccarino and Aleurotrachelus atratus Hempel were distributed in the northwestern zone adjoining the western ghats of Tamil Nadu. Coconut plantations at Sirumugai (western ghats) supported the most diverse collection of whiteflies, with 0.61 and 1.09 Simpson and Shannon diversity indices. Among the 29 districts, adjoining Dindigul and Theni districts showed the highest Bray–Curtis Similarity Matrix. Butterfly palm, Dypsis lutescens H. Wendel, custard apple, Annona squamosa L., and guava, Psidium guajava L., are whitefly hosts in coconut landscapes.

Faktor Pengelolaan Operasi dan Pemeliharaan Irigasi Di Kabupaten Tanah Datar

In recent years, the Tanah Datar district government has focused more on the physical implementation of irrigation area development and has not prioritized the budget for operating and maintenance costs so that there are still many Irrigation Areas (DI) whose irrigation infrastructure is not functioning properly with a high level of network damage that requires high costs. In addition, low awareness of the provision of operational and maintenance (OP) funds, limited human resources for OP staff, and the participation of groups of farmers using water (P3A) or a combination of groups of farmers using water (GP3A) is also not optimal. In order to function optimally and can be used for a long time, the irrigation that has been built needs to be maintained and managed systemically and to develop an optimal operating and maintenance management framework. The purpose of this study was to identify the dominant factors and factors that influence the operation and maintenance of irrigation networks in Tanah Datar District, as well as to optimize the operation and maintenance of the network. This study used a quantitative method by distributing questionnaires to respondents. The results of the research conducted revealed that there were 2 factors that influenced the operation and maintenance of irrigation networks in Tanah Datar Regency, namely the condition of physical infrastructure and supporting facilities and P3A Personnel Organization and Institutions..

Regular Sport Activity Is Able to Reduce the Level of Genomic Damage.

Regular physical activity is considered one of the most valid tools capable of reducing the risk of onset of many diseases in humans. However, it is known that intense physical activity can induce high levels of genomic damage, while moderate exercise can elicit a favorable adaptive response by the organism. We evaluated, by the buccal micronuclei assay, the frequencies of micronuclei, nuclear buds and binucleated cells in a sample of amateur athletes practicing different disciplines, comparing the obtained data with those of subjects who practiced sports just occasionally and subjects that did not practice sport at all. The aim was to evaluate whether physical activity affects background levels of genomic damage and whether the different sports disciplines, as well as some gene polymorphisms, differentially affect these levels. A total of 206 subjects, 125 athletes and 81 controls, were recruited. Athletes showed significantly lower values of micronuclei, nuclear buds and binucleated cells with respect to controls. Sprinters and Martial Artists displayed significantly higher frequencies of micronuclei than other categories of athletes. Finally, neither sex nor gene polymorphisms seemed to influence the levels of genomic damage, confirming that the observed genomic damage is probably due to the nature of the sport activity.

Failure analysis of a cracked tram axle

The subject of the paper is the results of the material analysis of the cracked axle of the tram. Fractographic analysis of the fracture surface was performed, the microstructure of the damaged part was observed, hardness profiles were measured and local chemical composition was determined by the EDX method. The failure occurred through a fatigue mechanism. The crack was initiated from surface defects of the welded material on the surface of the axle. The cause of the accident was the interplay of several negative factors: poor welding repair technology, unsuitable consumables, high levels of residual stresses and mechanical damage during assembly.

THE ATTACK OF THE WEEVIL Sitophilus granarius L. ON VARIETIES NEW WHEAT STORED

Stored cereal products suffer year after year from the attack of various insects, mainly due to the short period in which the grains are used. Instead, by delaying grain utilization, and especially in winter wheat, storage pests follow their biological cycle. This is also the case with the Sitophilus weevil whose attack causes a high level of damage every year. In this experiment, two series of batches of three varieties of winter wheat were analyzed. From the data obtained, it was found the existence of significant differences depending on the analyzed factor, namely, distinctly significant in the case of the group of varieties formed by Trivale, Ursita and Linia A4-10, significant in the variety FLD Caro, FDL Concurent, Șimnic 1619. At the same time, a significant connection was found between the first group of varieties with the four lots analyzed and insignificant in the case of the second group of winter wheat varieties

Actionable loss of SLF2 drives B‐cell lymphomagenesis and impairs the DNA damage response

The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. Exploiting the impaired DDR can be a promising therapeutic strategy; however, the mechanisms of inactivation and corresponding biomarkers are incompletely understood. Starting from an unbiased screening approach, we identified the SMC5‐SMC6 Complex Localization Factor 2 (SLF2) as a regulator of the DDR and biomarker for a B‐cell lymphoma (BCL) patient subgroup with an adverse prognosis. SLF2‐deficiency leads to loss of DDR factors including Claspin (CLSPN) and consequently impairs CHK1 activation. In line with this mechanism, genetic deletion of Slf2 drives lymphomagenesis in vivo. Tumor cells lacking SLF2 are characterized by a high level of DNA damage, which leads to alterations of the post‐translational SUMOylation pathway as a safeguard. The resulting co‐dependency confers synthetic lethality to a clinically applicable SUMOylation inhibitor (SUMOi), and inhibitors of the DDR pathway act highly synergistic with SUMOi. Together, our results identify SLF2 as a DDR regulator and reveal co‐targeting of the DDR and SUMOylation as a promising strategy for treating aggressive lymphoma.

Host–parasite coevolution and the stability of genetic kin recognition

Crozier's paradox suggests that genetic kin recognition will not be evolutionarily stable. The problem is that more common tags (markers) are more likely to be recognized and helped. This causes common tags to increase in frequency, eliminating the genetic variability that is required for genetic kin recognition. Two potential solutions to this problem have been suggested: host-parasite coevolution and multiple social encounters. We show that the host-parasite coevolution hypothesis does not work as commonly assumed. Host-parasite coevolution only stabilizes kin recognition at a parasite resistance locus if parasites adapt rapidly to hosts and cause intermediate or high levels of damage (virulence). Additionally, when kin recognition is stabilized at a parasite resistance locus, this can have an additional cost of making hosts more susceptible to parasites. However, we show that if the genetic architecture is allowed to evolve, meaning natural selection can choose the recognition locus, genetic kin recognition is more likely to be stable. The reason for this is that host-parasite coevolution can maintain tag diversity at another (neutral) locus by genetic hitchhiking, allowing that other locus to be used for genetic kin recognition. These results suggest a way that host-parasite coevolution can resolve Crozier's paradox, without making hosts more susceptible to parasites. However, the opportunity for multiple social encounters may provide a more robust resolution of Crozier's paradox.

Evaluating the genotoxicity of salinity stress and secondary products gene manipulation in lime, Citrus aurantifolia, plants.

Salinity is a significant abiotic stress that has a profound effect on growth, the content of secondary products, and the genotoxicity of cells. Lime, Citrus aurantifolia, is a popular plant belonging to the family Rutaceae. The interest in cultivating this plant is due to the importance of its volatile oil, which is included in many pharmaceutical industries, but C. aurantifolia plants are affected by the NaCl salinity levels. In the present study, a comet assay test has been applied to evaluate the genotoxic impact of salinity at 0, 50, 100, and 200 mM of NaCl on C. aurantifolia tissue-cultured plants. Furthermore, terpene gene expression was investigated using a semi-quantitative real-time polymerase chain reaction. Results from the two analyses revealed that 200 mM of NaCl stress resulted in high levels of severe damage to the C. aurantifolia plants' DNA tail 21.8%, tail length 6.56 µm, and tail moment 3.19 Unit. The relative highest expression of RtHK and TAT genes was 2.08, and 1.693, respectively, when plants were exposed to 200 mM of NaCl, whereas pv4CL2RT expressed 1.50 in plants subjected to 100 mM of NaCl. The accumulation of transcripts for the RTMYB was 0.951 when plants were treated with NaCl at 50 mM, and RtGPPS gene was significantly decreased to 0.446 during saline exposure at 100 mM. We conclude that the comet assay test offers an appropriate tool to detect DNA damage as well as RtHK, TAT, and pv4CL2RT genes having post-transcriptional regulation in C. aurantifolia plant cells under salinity stress. Future studies are needed to assess the application of gene expression and comet assay technologies using another set of genes that show vulnerability to different stresses on lime and other plants.

Adaptability and damage capacity of Spodoptera frugiperda J.E Smith (Lepidoptera: Noctuidae) on various Gramineae: a laboratory study

Spodoptera frugiferda is a pest that initially attacks corn plants in tropical and subtropical regions such as America. At the beginning of 2019, the S. frugiperda entered Indonesia and was first found to attack corn plants in Sumatra. In the same year 2019, the pest was also found attacking corn plants in Bali. Until now, the presence of these pests has spread to various parts of the world and is not limited to corn plants but also to other Graminae plants. This study aims to determine the type of alternative host plant S. frugiperda in other graminae families. This study used a Randomized Block Design (RBD) using six 5 types of host plants as treatments and five replications. Research on the adaptation of S. frugiperda to host plants was carried out in the laboratory, while observations of the level of damage to plants were carried out using the scoring method based on the percentage of attack area on the leaves. The results showed that S. frugiperda was only able to adapt to the four host plants tested, namely hybrid corn, sorghum and local rice, while hybrid rice and rice varieties of Ciherang were not selected, which was indicated by their preference for not choosing these plants as spawning sites. S. frugiperda showed the best selectivity level for hybrid maize as host. In general, the characteristics of the damage caused by S. frugiperda were almost the same in each of the test plants. The highest level of damage was found during the fourth observation on Hybrid Corn in the heavy category. Attacks and leaf damage were not found in Hybrid Rice and Ciherang Rice Varieties. The findings of this study are useful in predicting population dynamics of S. frugiperda especially in areas cultivating Graminae crops, to develop sustainable integrated pest management strategies for this pest.

Investigation of XPD, miR-145 and miR-770 expression in patients with end-stage renal disease.

The effective maintenance of genome integrity and fidelity is vital for the normal function of our tissues and organs, and the prevention of diseases. DNA repair pathways maintain genome stability, and the adequacy of genes acting in these pathways is essential for disease suppression and direct treatment responses. Chronic kidney disease is characterized by high levels of genomic damage. In this study, we examined the expression levels of the xeroderma pigmentosum group D (XPD) gene, which plays a role in the nucleotide excision repair (NER) repair mechanism, and the expression levels of miR-145 and miR-770 genes, which play a role in the regulation of the expression of the XPD gene, in hemodialysis patients with (n = 42) and without malignancy (n = 9) in pre- and post-dialysis conditions. We also evaluated these values with the clinical findings of the patients. Gene expression analysis was performed by real-time polymerase chain reaction (qRT-PCR). Compared to the individuals with normal kidney function (2.06 ± 0.32), the XPD gene expression was lower in the pre-dialysis condition both in hemodialysis patients without cancer (1.24 ± 0.18; p = 0.02) and in hemodialysis patients with cancer (0.82 ± 0.114; p = 0.001). On the other hand, we found that miR-145 and miR-770 expression levels were high in both groups. We also found that expression levels were affected by dialysis processes. A statistically significant positive correlation was found between miR-145 and mir770 expression levels in the pre-dialysis group of patients with (r=-0.988. p = 0.0001) and without (r=-0.934. p = 0.0001) malignancy. Studies on DNA damage repair in the kidney will help develop strategies to protect kidney function against kidney diseases.

The impact of TP53 activation and apoptosis in primary hereditary microcephaly.

Autosomal recessive primary microcephaly (MCPH) is a constellation of disorders that share significant brain size reduction and mild to moderate intellectual disability, which may be accompanied by a large variety of more invalidating clinical signs. Extensive neural progenitor cells (NPC) proliferation and differentiation are essential to determine brain final size. Accordingly, the 30 MCPH loci mapped so far (MCPH1-MCPH30) encode for proteins involved in microtubule and spindle organization, centriole biogenesis, nuclear envelope, DNA replication and repair, underscoring that a wide variety of cellular processes is required for sustaining NPC expansion during development. Current models propose that altered balance between symmetric and asymmetric division, as well as premature differentiation, are the main mechanisms leading to MCPH. Although studies of cellular alterations in microcephaly models have constantly shown the co-existence of high DNA damage and apoptosis levels, these mechanisms are less considered as primary factors. In this review we highlight how the molecular and cellular events produced by mutation of the majority of MCPH genes may converge on apoptotic death of NPCs and neurons, via TP53 activation. We propose that these mechanisms should be more carefully considered in the alterations of the sophisticated equilibrium between proliferation, differentiation and death produced by MCPH gene mutations. In consideration of the potential druggability of cell apoptotic pathways, a better understanding of their role in MCPH may significantly facilitate the development of translational approaches.

O-299 Sperm DNA fragmentation by TUNEL influences live birth in egg recipients after euploid embryo transfer

Abstract Study question Does sperm DNA fragmentation (SDF) by TUNEL affect reproductive success measured as live birth rate (LBR) in egg recipients after euploid embryo transfer? Summary answer SDF increases miscarriage rates in egg recipients with PGT-A. Therefore, live birth rates depends on sperm DNA damage in egg recipients after euploid embryo transfer. What is known already Sperm DNA integrity is important for optimal fertilisation, implantation and pregnancy. Although controversial, several studies have shown that sperm DNA fragmentation correlates with adverse pregnancy outcomes in infertile men. Ooplasmic sperm DNA fragmentation repair mechanisms may occur in female gametes, mainly in young women. However, research on the impact of DNA fragmentation on LBR are limited. Also, chromosomally normal embryos analysed by PGT-A offers opportunity to isolate female factor and study male factor. The aim of this study is to assess whether high level of semen DNA damage has an impact on reproductive outcomes in terms of live birth rate. Study design, size, duration This is a retrospective study of 467 PGT-A cycles in egg recipients. The study population consists of infertile couples for euploid embryo transfer (February 2017-November 2022). Semen samples were obtained to measure DNA damage from 447 men. PGT-A was performed in 1831 blastocysts. Trophectoderm biopsies (d5/d6 blastocysts) were analysed by NGS (Veriseq Illumina). Embryos were frozen and 568 blastocysts transferred in the subsequent cycle. Conventional hormone replacement was used for endometrial preparation in recipient patients. Participants/materials, setting, methods Cohort study with 447 infertile couples attending to private fertility clinic undergoing ART with their autologous semen, donated oocytes and PGT-A. SDF was measured by Terminal-deoxyribonucleotidyl-ARTSferase-mediated dUTP Nodule End Labelling (TUNEL) assay using the FITC-labelled-dUTP in situ cell death detection kit (Roche). The cohort was divided into two groups according the DNA fragmentation index (DFI): high SDF group (DFI>20%) and normal SDF group (DFI≤20%). To evaluate reproductive outcomes Chi-square and Linear regression tests were used. Main results and the role of chance Of the 447 couples included (average paternal age 41.29 + 7.32 years), 66.5% of male partners had normal semen parameters. We reported high sperm DNA fragmentation in 8% of patients. Overall, the embryo aneuploidy rate was 31.7%. For the further statistical analysis confounding factors such as, female and male age, embryo quality, day of embryo biopsy were included. PGT-A analysis showed an aneuploidy rate of 32.1% in the high DNA fragmentation group and 30.3% in the normal DNA fragmentation group (p = 0.453). Regarding clinical data, the overall implantation rate was 34.9%. There was no significant difference between elevate DNA fragmentation and normal DNA fragmentation with respect to biochemical miscarriage rate (4.3% vs 7.6%, p = 0.799). Although not significant differences between groups, a lower implantation rate near to reach significance was found in the high SDF group (20.0% vs 34.4%, p = 0.050). Pregnancy and clinical pregnancy rates were significantly lower in the high DNA fragmentation group (26.1% vs 44.9%, p = 0.042; 21.7% vs 31.3%, p = 0.044;), respectively. Also, miscarriage rate was significantly higher in the high SDF group (40% vs 12.5%, p = 0.014). Therefore, the live birth rate was significantly lower in the high SDF group (13.0% vs 32.6%, p = 0.024). Limitations, reasons for caution Larger studies including a higher number of samples are needed to confirm the correlation observed between LBR in eggs recipients with semen DNA fragmentation. Those patients with a DFI higher than control values should be treated with antioxidants. The pregnancy outcomes should be analyzed after treatment of DNA fragmentation. Wider implications of the findings Our findings suggest that autologous semen DNA fragmentation influence in live birth rate in egg recipients. Our data show that live birth rates decreased in patients with a high DFI after PGT-A. This study confirms published studies in the literature showing that ART outcomes are affected by sperm DNA fragmentation. Trial registration number Not Applicable