1. Bisphenol A in the urine : association with urinary creatinine, impaired kidney function, use of plastic food and beverage storage products but not with serum anti-müllerian hormone in ovarian malignanciesMateja Sladič, Špela Smrkolj, Gorazd Kavšek, Senka Imamović-Kumalić, Ivan Verdenik, Irma Virant-Klun, 2025, izvirni znanstveni članek Povzetek: Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits.
Ključne besede: anti-Müllerian hormone, kidney function, lifestyle habits, ovarian cancer, thrombocytes, urine, female exposure
Objavljeno v DiRROS: 03.12.2025; Ogledov: 912; Prenosov: 157
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2. Nontargeted urinary profiling strategy for endocrine-disrupting chemicals in women with ovarian malignanciesHelena Plešnik, Žan Rekar, Stefanela Stevanović, Irma Virant-Klun, Senka Imamović-Kumalić, Mateja Sladič, Darja Mazej, Janja Snoj Tratnik, Milena Horvat, Tina Kosjek, 2025, izvirni znanstveni članek Povzetek: Endocrine-disrupting chemicals (EDCs), includingknown and unknown parent compounds, their metabolites, andtransformation products, are pervasive in daily life, posingincreasing risks to human health and the environment. Thisstudy employed a high-resolution mass spectrometry-basednontargeted screening approach, integrating polar (HILIC) andreversed-phase separations to expand the chemical space coverageand, supported by open-science tools and resources, evaluatedurinary chemical profiles to assess internal EDC exposure. Among106 annotated biomarkers of exposure, six exhibited significantlyhigher normalized intensities in patients with ovarian malignanciescompared to healthy controls (p < 0.05). This suggests theirgreater exposure to phthalates (diethylhexyl phthalate and diethylphthalate), pesticides (metolachlor metabolite and 4-nitrophenol), a UV filter (benzophenone-1), and an industrial byproduct (4-methyl-2-nitrophenol). These compounds may interfere with hormonal regulation, potentially contributing to cancer development.While these findings highlight potential differences in internal EDC exposure, the study primarily demonstrates the applicability ofnontargeted urinary profiling for chemical exposure assessment. By providing new insights into EDCs burden and its pathologicalimplications, this work contributes to advancing next-generation chemical risk assessment within the European Partnership for theAssessment of Risks from Chemicals initiative and supports the development of preventive strategies to mitigate environmentalcancer risks
Ključne besede: ovarian cancer, biomarkers, exposure, nontargeted screening, high-resolution mass spectrometry, analytical coverage, reversed-phase, HILIC
Objavljeno v DiRROS: 02.12.2025; Ogledov: 452; Prenosov: 170
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3. Bisphenol a disrupts steroidogenesis and induces apoptosis in human granulosa cells cultured in vitroDominika Celar Šturm, Tadeja Režen, Nina Jančar, Irma Virant-Klun, 2025, izvirni znanstveni članek Povzetek: Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 µM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 µM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 µM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations.
Ključne besede: bisphenol A, human granulosa cells, steroidogenesis, apoptosis, steroid hormones
Objavljeno v DiRROS: 13.11.2025; Ogledov: 342; Prenosov: 173
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4. Associations of essential and non-essential trace elements’ levels in the blood, serum, and urine in women with premature ovarian insufficiencyTina Kek, Ksenija Geršak, Nataša Karas Kuželički, Dominika Celar Šturm, Darja Mazej, Janja Snoj Tratnik, Ingrid Falnoga, Milena Horvat, Irma Virant-Klun, 2025, izvirni znanstveni članek Povzetek: Premature ovarian insufficiency (POI) is poorly understood, with causes identified in only 25% of cases. Emerging evidence suggests links between trace elements (TEs) and POI. This study is the first to compare concentrations of manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) across urine, serum, and whole blood in women with POI compared to healthy controls (HC), aiming to explore their distribution and potential associations with POI. This cross-sectional-case-control study enrolled 81 participants (40 POI patients and 41 healthy controls) at the University Medical Centre Ljubljana, Slovenia. Blood and urine samples were collected to quantify basic biochemical parameters using standard clinical chemistry methods and concentrations of Mn, Cu, Zn, Se, Mo, As, Cd, Hg, and Pb using inductively coupled plasma-mass spectrometry (ICP-MS). Participants also completed questionnaires on socio-demographics, medical history, lifestyle, and nutrition. Data was analyzed using the Mann–Whitney U test, Student's t-tests, Fisher exact test, logistic regression models adjusted on body mass index (BMI), age, hematocrit, and Kendall's tau correlation. Women with POI had significantly higher BMI and red blood cell (RBC) indices, including hemoglobin, hematocrit, and red cell distribution width (RDW), compared to controls. A larger proportion of POI patients resided in rural agricultural areas. Liver and kidney function assessments showed no significant differences between the groups. Adjusted models revealed that POI patients had significantly lower urinary levels of Cu, Zn, Se, Mo, Cd, Hg, and Pb than controls, while whole blood Mn levels were higher. Serum Cu levels were significantly elevated in POI patients, whereas Pb, Cd, and Hg were lower. No significant differences were observed for As. Correlation analysis showed several strong to moderate associations among TEs across biofluids, but only weak correlations were found between TEs and demographic or biochemical factors. This study suggests potential associations between TEs and POI in women. Notably, most TEs (Zn, Se, Cu, Mo, Cd, Hg, Pb) were significantly lower in the urine of the POI group, while Cu, Cd, Hg, and Pb showed significant differences in both urine and serum.
Ključne besede: premature ovarian insufciency, essential, non-essential trace elements, biofuids, reproductive health
Objavljeno v DiRROS: 12.11.2025; Ogledov: 375; Prenosov: 164
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5. Clinical and structural features of sperm head vacuoles in men included in the in vitro fertilization programmeNina Fekonja, Jasna Štrus, Magda Tušek-Žnidarič, Katja Knez, Eda Vrtačnik-Bokal, Ivan Verdenik, Irma Virant-Klun, 2014, izvirni znanstveni članek Povzetek: The human sperm head vacuoles and their role in male infertility are still poorly understood. The aim of this study was to identify the clinical and ultrastructural features of human sperm head vacuoles in men included in the in vitro fertilization programme: men with normal (normozoospermia) and impaired sperm morphology (teratozoospermia). The sperm samples were observed under 6000-time magnification using motile sperm organelle morphology examination (MSOME). The proportion of sperm with head vacuoles was evaluated and related to the outcome of in vitro fertilization. The sperm of men with impaired sperm morphology was characterized by a higher proportion of sperm head vacuoles. The sperm head vacuoles were related to impaired semen quality (sperm concentration, motility, and morphology) but were not influenced by male factors (semen volume, height, age, weight, or body mass index). Moreover, sperm head vacuoles were related to impaired fertilization rate merely after classical in vitro fertilization (IVF), while there was no relation to pregnancy. In a subgroup of men, the sperm was fixed and observed by transmission electron microscopy (TEM). The ultrastructural study revealed that sperm head vacuoles are large nuclear indentations of various sizes and positions, packed with membranous material organized in membrane whorls (MW).
Ključne besede: human sperm head vacuoles, male infertility
Objavljeno v DiRROS: 04.03.2025; Ogledov: 697; Prenosov: 780
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7. Effect of the oral intake of astaxanthin on semen parameters in patients with oligo-astheno-teratozoospermia : a randomized double-blind placebo-controlled trialSenka Imamović-Kumalić, Irma Virant-Klun, Eda Vrtačnik-Bokal, Bojana Pinter, 2021, izvirni znanstveni članek Povzetek: Background Higher concentrations of seminal reactive oxygen species may be related to male infertility. Astaxanthin with high antioxidant activity can have an impact on the prevention and treatment of various health conditions, including cancer. However, efficacy studies on astaxanthin in patients with oligospermia with/without astheno- or teratozoospermia (O+-A+-T) have not yet been reported. Our aim was to evaluate the effect of the oral intake of astaxanthin on semen parameters. Patients and methods In a randomized double-blind trial, 80 men with O+-A+-T were allocated to intervention with 16 mg astaxanthin orally daily or placebo. At baseline and after three months basic semen parameters, sperm deoxyribonucleic acid (DNA) fragmentation and mitochondrial membrane potential (MMP) of spermatozoa and serum follicle-stimulating hormone (FSH) value were measured. Results Analysis of the results of 72 patients completing the study (37 in the study group, 35 in the placebo group) did not show any statistically significant change, in the astaxanthin group no improvements in the total number of spermatozoa, concentration of spermatozoa, total motility of spermatozoa, morphology of spermatozoa, DNA fragmentation and mitochondrial membrane potential of spermatozoa or serum FSH were determined. In the placebo group, statistically significant changes in the total number and concentration of spermatozoa were determined. Conclusions The oral intake of astaxanthin did not affect any semen parameters in patients with O+-A+-T.
Ključne besede: DNA fragmentation, antioxidant, cancer
Objavljeno v DiRROS: 17.07.2024; Ogledov: 1091; Prenosov: 656
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