Genotoxicity Assessment of Quinoin, a Ribosome Inactivating Protein from Quinoa Seeds, in the Teleost Danio rerio.

BACKGROUND: Ribosome inactivating proteins (RIPs) are N-glycosylases found in various plants that are able to specifically and irreversibly inhibit protein translation, thereby leading to cell death. Their cytotoxic properties have attracted attention in the medical field in the context of developing new anticancer therapies. Quinoin is a novel toxic enzyme obtained from quinoa seeds and classified as a type 1 RIP (Chenopodium quinoa Willd.). Recently, quinoin was found to be cytotoxic to normal fibroblasts and keratinocytes in vitro, as well as to several tumor cell lines. METHODS: The aim of this study was to evaluate the in vitro and in vivo genotoxicity of quinoin in a zebrafish model. We evaluated its ability to induce DNA fragmentation, genomic instability, and reactive oxygen species (ROS) generation by means of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction, randomly amplified polymorphic DNA (RAPD) Polymerase Chain Reaction (PCR) technique, and dichlorofluorescine (DCF) assay, respectively. RESULTS: Quinoin was found to cause genomic damage in zebrafish, as shown by DNA fragmentation, polymorphic variations leading to genomic instability, and oxidative stress. Interestingly, longer quinoin treatment caused less damage than shorter treatments. CONCLUSIONS: This study demonstrated ROS-mediated genotoxicity of quinoin toward the zebrafish genome. The reduced damage observed after longer quinoin treatment could indicate the activation of detoxification mechanisms, activation of repair mechanisms, or the loss of protein activity due to enzymatic digestion. In order to clarify the genotoxic actions of quinoin, further investigations of the response pathways to DNA damage are needed. Overall, the ability of quinoin to cause breaks and instability in DNA, together with its clear cytotoxicity, make it an interesting candidate for the development of new drugs for cancer treatment.

Environmental and Genetic Traffic in the Journey from Sperm to Offspring.

Recent advancements in the understanding of how sperm develop into offspring have shown complex interactions between environmental influences and genetic factors. The past decade, marked by a research surge, has not only highlighted the profound impact of paternal contributions on fertility and reproductive outcomes but also revolutionized our comprehension by unveiling how parental factors sculpt traits in successive generations through mechanisms that extend beyond traditional inheritance patterns. Studies have shown that offspring are more susceptible to environmental factors, especially during critical phases of growth. While these factors are broadly detrimental to health, their effects are especially acute during these periods. Moving beyond the immutable nature of the genome, the epigenetic profile of cells emerges as a dynamic architecture. This flexibility renders it susceptible to environmental disruptions. The primary objective of this review is to shed light on the diverse processes through which environmental agents affect male reproductive capacity. Additionally, it explores the consequences of paternal environmental interactions, demonstrating how interactions can reverberate in the offspring. It encompasses direct genetic changes as well as a broad spectrum of epigenetic adaptations. By consolidating current empirically supported research, it offers an exhaustive perspective on the interwoven trajectories of the environment, genetics, and epigenetics in the elaborate transition from sperm to offspring.

Green Synthesis and Characterization of Novel Silver Nanoparticles Using Achillea maritima subsp. maritima Aqueous Extract: Antioxidant and Antidiabetic Potential and Effect on Virulence Mechanisms of Bacterial and Fungal Pathogens.

Novel silver nanoparticles were synthesized based on a simple and non-toxic method by applying the green synthesis technique, using, for the first time, the aqueous extract of an extremophile plant belonging to the Achillea maritima subsp. maritima species. AgNP characterization was performed via UV-Visible, front-face fluorescence spectroscopy, and FTIR and XRD analyses. AgNP formation was immediately confirmed by a color change from yellow to brown and by a surface plasmon resonance peak using UV-Vis spectroscopy at 420 nm. The biosynthesized AgNPs were spherical in shape with a size ranging from approximatively 14.13 to 21.26 nm. The presented silver nanoparticles exhibited strong antioxidant activity following a DPPH assay compared to ascorbic acid, with IC50 values of about 0.089 µg/mL and 22.54 µg/mL, respectively. The AgNPs showed higher antidiabetic capacities than acarbose, by inhibiting both alpha amylase and alpha glucosidase. The silver nanoparticles could affect various bacterial mechanisms of virulence, such as EPS production, biofilm formation and DNA damage. The silver nanoparticles showed no lysozyme activity on the cell walls of Gram-positive bacteria. The AgNPs also had a strong inhibitory effect on the Candida albicans virulence factor (extracellular enzymes, biofilm formation). The microscopic observation showed abnormal morphogenesis and agglomeration of Candida albicans exposed to AgNPs. The AgNPs showed no cytotoxic effect on human cells in an MTT assay. The use of novel silver nanoparticles is encouraged in the formulation of natural antimicrobial and antidiabetic agents.

Polymorphic Rearrangements of Human Chromosome 9 and Male Infertility: New Evidence and Impact on Spermatogenesis.

Chromosomal polymorphisms are structural variations in chromosomes that define the genomic variance of a species. These alterations are recurrent in the general population, and some of them appear to be more recurrent in the infertile population. Human chromosome 9 is highly heteromorphic, and how its rearrangement affects male fertility remains to be fully investigated. In this study, we aimed to investigate the association between the polymorphic rearrangements of chromosome 9 and male infertility via an Italian cohort of male infertile patients. Cytogenetic analysis was carried out, along with Y microdeletion screening, semen analysis, fluorescence in situ hybridization, and TUNEL assays using spermatic cells. Chromosome 9 rearrangements were observed in six patients: three of them showed a pericentric inversion, while the others showed a polymorphic heterochromatin variant 9qh. Of these, four patients exhibited oligozoospermia associated with teratozoospermia, along with a percentage of aneuploidy in the sperm of above 9%, in particular, an increase in XY disomy. Additionally, high values for sperm DNA fragmentation (≥30%) were observed in two patients. None of them had microdeletions to the AZF loci on chromosome Y. Our results suggest that polymorphic rearrangements of chromosome 9 might be associated with abnormalities in sperm quality due to incorrect spermatogenesis regulation.

Production and Characterization of New Biosurfactants/Bioemulsifiers from Pantoea alhagi and Their Antioxidant, Antimicrobial and Anti-Biofilm Potentiality Evaluations.

The present work aimed to develop rapid approach monitoring using a simple selective method based on a positive hemolysis test, oil spreading activity and emulsification index determinations. It is the first to describe production of biosurfactants (BS) by the endophytic Pantoea alhagi species. Results indicated that the new BS evidenced an E24 emulsification index of 82%. Fourier-transform infrared (FTIR) results mentioned that the described BS belong to the glycolipid family. Fatty acid profiles showed the predominance of methyl 2-hyroxydodecanoate in the cell membrane (67.00%) and methyl 14-methylhexadecanoate (12.05%). The major fatty acid in the BS was oleic acid (76.26%), followed by methyl 12-methyltetradecanoate (10.93%). Markedly, the BS produced by the Pantoea alhagi species exhibited antimicrobial and anti-biofilm activities against tested human pathogens. With superior antibacterial activity against Escherchia coli and Staphylococcus aureus, a high antifungal effect was given against Fusarium sp. with a diameter of zone of inhibition of 29.5 mm, 36 mm and 31 mm, obtained by BS dissolved in methanol extract. The DPPH assay indicated that the BS (2 mg/mL) showed a higher antioxidant activity (78.07 inhibition percentage). The new BS exhibited specific characteristics, encouraging their use in various industrial applications.

Polycystic Ovary Syndrome: An Updated Overview Foregrounding Impacts of Ethnicities and Geographic Variations.

Polycystic ovary syndrome (PCOS) is one of the most common heterogeneous conditions of the endocrine reproductive system in women of childbearing age. Hyperandrogenism and oligomenorrhea are the two core characteristics of PCOS, a complicated and multifaceted illness. The condition is also linked to several major side effects, which include type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. There are few facts and statistics available on PCOS prevalence internationally due to the significant degree of geographic and ethnic variance and inconsistency caused by different diagnosis standards. Limited (n = 179) explorations have been made in the context of the prevalence of this complicated illness so far, and out of these, only 55 studies have discussed its association with race and/or ethnicity. However, those studies remain restricted due to the small sample size, biased selection, and the lack of comparative studies. Variations in PCOS prevalence frequency also arise due to different diagnostic criteria, as well as racial and ethnic differences, associated lifestyle factors, and subsequent illnesses that affect the accuracy of the diagnosis. The main objective behind this systematic review is to provide comprehensive epidemiological data on PCOS that is organized geographically. This evidence-based study also provides an overview of the clinical management of PCOS to instigate further research on this complex endocrinological condition and the subsequent development of preventive treatment strategies.

In Vitro Combination of Ascorbic and Ellagic Acids in Sperm Oxidative Damage Inhibition.

It is known that an altered redox balance interferes with normal spermatic functions. Exposure to genotoxic substances capable of producing oxidative stress (OS) can cause infertility in humans. The use of antioxidants to reduce oxidative stress contributes to the improvement in reproductive function. This study focused on an antigenotoxic evaluation of ellagic acid (EA) and ascorbic acid (AA) in combination against benzene genotoxic action on human spermatozoa in vitro. In addition to the evaluation of sperm parameters, damage in sperm genetic material and intracellular ROS quantification were assessed after AA, EA and benzene co-exposure using the TUNEL technique and DCF assay. The results showed that the combination of the two antioxidants generates a greater time-dependent antigenotoxic action, reducing both the sperm DNA fragmentation index and the oxidative stress. The genoprotective effect of AA and EA association in sperm cells lays the foundations for a more in-depth clinical study on the use of antioxidants as a therapy for male infertility.

First Report of the Biosynthesis and Characterization of Silver Nanoparticles Using Scabiosa atropurpurea subsp. maritima Fruit Extracts and Their Antioxidant, Antimicrobial and Cytotoxic Properties.

Candida and dermatophyte infections are difficult to treat due to increasing antifungal drugs resistance such as fluconazole, as well as the emergence of multi-resistance in clinical bacteria. Here, we first synthesized silver nanoparticles using aqueous fruit extracts from Scabiosa atropurpurea subsp. maritima (L.). The characterization of the AgNPs by means of UV, XRD, FTIR, and TEM showed that the AgNPs had a uniform spherical shape with average sizes of 40-50 nm. The biosynthesized AgNPs showed high antioxidant activity when investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The AgNPs displayed strong antibacterial potential expressed by the maximum zone inhibition and the lowest MIC and MBC values. The AgNPs revealed a significant antifungal effect against the growth and biofilm of Candida species. In fact, the AgNPs were efficient against Trichophyton rubrum, Trichophyton interdigitale, and Microsporum canis. The antifungal mechanisms of action of the AgNPs seem to be due to the disruption of membrane integrity and a reduction in virulence factors (biofilm and hyphae formation and a reduction in germination). Finally, the silver nanoparticles also showed important cytotoxic activity against the human multiple myeloma U266 cell line and the human breast cancer cell line MDA-MB-231. Therefore, we describe new silver nanoparticles with promising biomedical application in the development of novel antimicrobial and anticancer agents.

Evaluation of Zebrafish DNA Integrity after Individual and Combined Exposure to TiO2 Nanoparticles and Lincomycin.

Environmental contamination by nanoparticles (NPs) and drugs represents one of the most debated issues of the last years. The aquatic biome and, indirectly, human health are strongly influenced by the negative effects induced by the widespread presence of pharmaceutical products in wastewater, mainly due to the massive use of antibiotics and inefficient treatment of the waters. The present study aimed to evaluate the harmful consequences due to exposure to antibiotics and NPs, alone and in combination, in the aquatic environment. By exploiting some of their peculiar characteristics, such as small size and ability to bind different types of substances, NPs can carry drugs into the body, showing potential genotoxic effects. The research was conducted on zebrafish (Danio rerio) exposed in vivo to lincomycin (100 mg/L) and titanium dioxide nanoparticles (TiO2 NPs) (10 µg/L) for 7 and 14 exposure days. The effects on zebrafish were evaluated in terms of cell viability, DNA fragmentation, and genomic template stability (GTS%) investigated using Trypan blue staining, TUNEL assay, and the random amplification of polymorphic DNA PCR (RAPD PCR) technique, respectively. Our results show that after TiO2 NPs exposure, as well as after TiO2 NPs and lincomycin co-exposure, the percentage of damaged DNA significantly increased and cell viability decreased. On the contrary, exposure to lincomycin alone caused only a GTS% reduction after 14 exposure days. Therefore, the results allow us to assert that genotoxic effect in target cells could be through a synergistic effect, also potentially mediated by the establishment of intermolecular interactions between lincomycin and TiO2 NPs.

State of the art on the physical mapping of the Y-chromosome in the Bovidae and comparison with other species - A review.

The next generation sequencing has significantly contributed to clarify the genome structure of many species of zootechnical interest. However, to date, some portions of the genome, especially those linked to a heterogametic nature such as the Y chromosome, are difficult to assemble and many gaps are still present. It is well known that the fluorescence in situ hybridization (FISH) is an excellent tool for identifying genes unequivocably mapped on chromosomes. Therefore, FISH can contribute to the localization of unplaced genome sequences, as well as to correct assembly errors generated by comparative bioinformatics. To this end, it is necessary to have starting points; therefore, in this study, we reviewed the physically mapped genes on the Y chromosome of cattle, buffalo, sheep, goats, pigs, horses and alpacas. A total of 208 loci were currently mapped by FISH. 89 were located in the malespecific region of the Y chromosome (MSY) and 119 were identified in the pseudoautosomal region (PAR). The loci reported in MSY and PAR were respectively: 18 and 25 in Bos taurus, 5 and 7 in Bubalus bubalis, 5 and 24 in Ovis aries, 5 and 19 in Capra hircus, 10 and 16 in Sus scrofa, 46 and 18 in Equus caballus. While in Vicugna pacos only 10 loci are reported in the PAR region. The correct knowledge and assembly of all genome sequences, including those of genes mapped on the Y chromosome, will help to elucidate their biological processes, as well as to discover and exploit potentially epistasis effects useful for selection breeding programs.

Comprehensive Analysis of Global Research on Human Varicocele: A Scientometric Approach.

PURPOSE: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. MATERIALS AND METHODS: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software. RESULTS: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature. CONCLUSIONS: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele's impact on men's health and male fertility.

TiO2-NPs and cadmium co-exposure: in vitro assessment of genetic and genomic DNA damage on Dicentrarchus labrax embryonic cells.

The increased titanium dioxide nanoparticles (TiO2-NPs) spread and their interaction with organic and inorganic pollutants arouses concern for the potential hazards for organisms and environment. This study tested in vitro the genotoxic effects of TiO2-NPs (1 µg/mL) and cadmium (Cd) (0.1 µg/mL) co-exposure using Dicentrarchus labrax embryonic cells (DLEC) as experimental model. The genotoxicity tests (Comet assay, Diffusion Assay and Random Amplification of Polymorphic DNA (RAPD-PCR) were conducted after 3, 24 and 48 hours of exposure to TiO2-NPs and Cd alone and in combination. The results showed that the percentage of DNA damage and apoptotic cells increases following 48 hours TiO2-NPs exposure, while DNA instability was detected for all the times tested. Cd induced genotoxic effects starting from 3 hour-exposure and for all the treatment times. Cd + TiO2-NPs co-exposure did not cause any genomic damage or apoptosis for all the exposure times. The possibility that Cd and TiO2-NPs form aggregates no longer able of penetrating the nucleus and damaging the genetic material is discussed.

Biosynthesis and Characterization of Silver Nanoparticles from the Extremophile Plant Aeonium haworthii and Their Antioxidant, Antimicrobial and Anti-Diabetic Capacities.

The present paper described the first green synthesis of silver nanoparticles (AgNPs) from the extremophile plant Aeonium haworthii. The characterization of the biosynthesized silver nanoparticles was carried out by using UV-Vis, FTIR and STM analysis. The antioxidant, antidiabetic and antimicrobial properties were also reported. The newly described AgNPs were spherical in shape and had a size of 35-55 nm. The lowest IC50 values measured by the DPPH assay indicate the superior antioxidant behavior of our AgNPs as opposed to ascorbic acid. The silver nanoparticles show high antidiabetic activity determined by the inhibitory effect of α amylase as compared to the standard Acarbose. Moreover, the AgNPs inhibit bacterial growth owing to a bactericidal effect with the MIC values varying from 0.017 to 1.7 µg/mL. The antifungal action was evaluated against Candida albicans, Candida tropicalis, Candida glabrata, Candida sake and non-dermatophytic onychomycosis fungi. A strong inhibitory effect on Candida factors' virulence was observed as proteinase and phospholipase limitations. In addition, the microscopic observations show that the silver nanoparticles cause the eradication of blastospores and block filamentous morphogenesis. The combination of the antioxidant, antimicrobial and antidiabetic behaviors of the new biosynthesized silver nanoparticles highlights their promising use as natural phytomedicine agents.

DNA Damage in Human Amniotic Cells: Antigenotoxic Potential of Curcumin and α-Lipoic Acid.

Oxidative imbalances in the gestational phase are responsible for certain complications during pregnancy and for foetal and neonatal genetic disorders. In this work, using human amniocytes, we aimed to evaluate the protection provided to foetal DNA by two concentrations of antioxidant molecules, α-lipoic acid (LA) and curcumin (Cur), against hydrogen peroxide (H2O2)-induced damage. Genotoxicity tests, performed by the random amplification of polymorphic DNA (RAPD-PCR) technique and TUNEL tests, showed that the lowest concentration of LA-protected cells and DNA from H2O2 insults. However, a greater ability to protect the amniocytes' DNA against H2O2 was observed following co-treatment with the highest concentration of Cur with H2O2. In fact, a genomic template stability (GTS%) similar to that of the negative control and a statistically significant reduction in the DNA fragmentation index (DFI) were revealed. Moreover, following a combined treatment with both antioxidants and H2O2, no statistical difference from controls was observed, in terms of both induced mutations and DNA breaks. Furthermore, no effect on morphology or cell viability was observed. The results demonstrate the ability of LA and Cur to protect the genetic material of amniocytes against genotoxic insults, suggesting their beneficial effects in pathologies related to oxidative stress.

Protective Effects of Curcumin on the Outcome of Cryopreservation in Human Sperm.

Cryopreservation causes decreased sperm fertility potential due to reactive oxygen species (ROS) production and physical-chemical damage, resulting in reduced sperm viability and motility. The addition of antioxidants to freezing media could protect sperm from cryo-damage, counteracting the harmful effects of ROS. The aim of this study was to assess the effects of curcumin supplementation in freezing medium on preventing cryo-damage in human semen. Semen samples collected from fertile men were cryopreserved in freezing medium supplemented with different concentrations of curcumin (2.5, 5, 10, and 20 µM). After freezing-thawing, sperm parameters, DNA fragmentation, intracellular ROS, and glutathione peroxidase 4 (GPX4) gene expression were evaluated. Supplementation with 20 µM curcumin in freezing medium caused increases in progressive and nonprogressive motility and significant reductions in intracellular ROS and DNA fragmentation in frozen-thawed sperm cells. Following cryopreservation, GPX4 mRNA expression was significantly upregulated in thawed semen supplemented with 20 µM curcumin compared to the control. The results showed that curcumin supplementation in freezing medium was protective against human sperm parameters and sperm DNA, counteracting oxidative damage induced by the freeze-thaw process.

In vitro ameliorative effects of ellagic acid on vitality, motility and DNA quality in human spermatozoa.

Oxidative stress (OS) plays a significant role in the etiology of male infertility, resulting in the impairment of male reproduction. This condition, characterized by an imbalance in the levels of oxidizing and antioxidant species in the seminal fluid, has a harmful impact on sperm functions and DNA integrity. The present study aimed to evaluate the anti-genotoxic action of ellagic acid, a polyphenolic molecule of natural origin having a powerful antigenotoxic, anti-inflammatory and antiproliferative role. An OS condition was induced in vitro by incubating normozoospermic human semen samples in benzene for 45, 60 and 90 min. DNA integrity was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay, RAPD-PCR was performed to calculate the genome template stability, while the percentage of intracellular reactive oxygen species (ROS) was assessed by the 2', 7'-dichlorofluorescein assay. Our results showed that ellagic acid has a consistent protective effect on DNA integrity, as well as on sperm vitality and motility, by counteracting generation of intracellular ROS. The results of this study suggest ellagic acid as a suitable molecule to protect sperm DNA from oxidative stress, with a potentially significant translational impact on the management of the male infertility.

Adsorption of Cd to TiO2-NPs Forms Low Genotoxic AGGREGATES in Zebrafish Cells.

The aquatic environment is involved in the pollutants spreading mechanisms, including nanomaterials and heavy metals. The aims of this study were to assess the in vivo genotoxicity of Cd (1 mg/L) and to investigate the genomic effects generated by its co-exposure with TiO2-NPs (10 µg/L). The study was performed using zebrafish as a model for 5, 7, 14, 21, and 28 days of exposure. The genotoxic potential was assessed by three experimental approaches: DNA integrity, degree of apoptosis, and molecular alterations at the genomic level by genomic template stability (% GTS) calculation. Results showed an increased in DNA damage after Cd exposure with a decrease in % GTS. The co-exposure (TiO2-NPs + Cd) induced a no statistically significant loss of DNA integrity, a reduction of the apoptotic cell percentage and the recovery of genome stability for prolonged exposure days. Characterization and analytical determinations data showed Cd adsorption to TiO2-NPs, which reduced free TiO2-NPs levels. The results of our study suggest that TiO2-NPs could be used for the development of controlled heavy metal bioremediation systems.

Impact of Alcohol Consumption on Male Fertility Potential: A Narrative Review.

Alcohol abuse disorder is a serious condition, implicating more than 15 million people aged 12 years and older in 2019 in the United States. Ethanol (or ethyl alcohol) is mainly oxidized in the liver, resulting in the synthesis of acetaldehyde and acetate, which are toxic and carcinogenic metabolites, as well as in the generation of a reductive cellular environment. Moreover, ethanol can interact with lipids, generating fatty acid ethyl esters and phosphatidylethanol, which interfere with physiological cellular pathways. This narrative review summarizes the impact of excessive alcohol consumption on male fertility by describing its metabolism and how ethanol consumption may induce cellular damage. Furthermore, the impact of alcohol consumption on hormonal regulation, semen quality, and genetic and epigenetic regulations is discussed based on evidence from animal and human studies, focusing on the consequences on the offspring. Finally, the limitations of the current evidence are discussed. Our review highlights the association between chronic alcohol consumption and poor semen quality, mainly due to the development of oxidative stress, as well as its genotoxic impact on hormonal regulation and DNA integrity, affecting the offspring's health. New landscapes of investigation are proposed for the identification of molecular markers for alcohol-associated infertility, with a focus on advanced OMICS-based approaches applied to the analysis of semen samples.

In Vitro Effects of Titanium Dioxide Nanoparticles (TiO2NPs) on Cadmium Chloride (CdCl2) Genotoxicity in Human Sperm Cells.

The environmental release of titanium dioxide nanoparticles (TiO2NPs) associated with their intensive use has been reported to have a genotoxic effect on male fertility. TiO2NP is able to bind and transport environmental pollutants, such as cadmium (Cd), modifying their availability and/or toxicity. The aim of this work is to assess the in vitro effect of TiO2NPs and cadmium interaction in human sperm cells. Semen parameters, apoptotic cells, sperm DNA fragmentation, genomic stability and oxidative stress were investigated after sperm incubation in cadmium alone and in combination with TiO2NPs at different times (15, 30, 45 and 90 min). Our results showed that cadmium reduced sperm DNA integrity, and increased sperm DNA fragmentation and oxidative stress. The genotoxicity induced by TiO2NPs-cadmium co-exposure was lower compared to single cadmium exposure, suggesting an interaction of the substances to modulate their reactivity. The Quantitative Structure-Activity Relationship (QSAR) computational method showed that the interaction between TiO2NPs and cadmium leads to the formation of a sandwich-like structure, with cadmium in the middle, which results in the inhibition of its genotoxicity by TiO2NPs in human sperm cells.