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Öğe A multidimensional follicular profile integrating oxidative stress, apoptosis and PI3K/AKT/mTOR signaling in relation to oocyte developmental competence in in vitro fertilization cycles(Springer/Plenum Publishers, 2026) Korkmaz, Oya; Karabulut, Seda; Macit, Pelin; Keskin, IlknurPurpose Accurate assessment of oocyte developmental competence remains challenging in IVF, as morphology alone offers limited insight into intrinsic oocyte quality. Emerging evidence indicates that oocyte competence reflects coordinated regulation of the follicular microenvironment rather than a single biomarker. This study aimed to evaluate a multidimensional follicular marker panel integrating oxidative stress parameters, hormonal environment, granulosa cell apoptosis, chromatin integrity and PTEN/PI3K/AKT/mTOR signaling in relation to IVF outcomes. Methods Thirty women undergoing ICSI were included, yielding a total of 211 oocytes. Individual follicles were analyzed according to oocyte maturity, embryo quality and pregnancy outcome. Follicular fluid oxidative stress parameters (TAC, TOC, OSI and MDA) and hormonal mediators (FSH, AMH, melatonin, TGF-beta and beta-hCG) were assessed. Granulosa cells were evaluated for DNA fragmentation, chromatin integrity and expression of PTEN/PI3K/AKT/mTOR pathway proteins. Results Favorable IVF outcomes were associated with higher total antioxidant capacity and lower oxidative stress index and malondialdehyde levels, alongside reduced granulosa cell DNA fragmentation and improved chromatin integrity (p < 0.05). These outcomes were characterized by increased PI3K and AKT expression with concomitant mTOR suppression, while PTEN, PDK1, TSC1 and TSC2 levels remained unchanged. Follicular FSH and AMH were primarily linked to oocyte maturity, whereas melatonin, TGF-beta and beta-hCG were elevated in follicles yielding good-quality embryos and positive pregnancy outcomes (p < 0.05). Conclusions Oocyte developmental competence in IVF reflects a coordinated follicular microenvironment integrating oxidative balance, granulosa cell integrity, hormonal regulation, and PI3K/AKT/mTOR signaling, supporting a multidimensional, panel-based framework for integrated follicular assessment.Öğe Association of NOX5 Expression with Sperm Activity and Motility in Pathospermic Infertile Men(Avicenna Research Institute, 2024) Daylan, Benay; Korkmaz, Oya; Tok, Olgu Enis; Cakici, Cagri; Yigitbasi, Turkan; Karahasanoglu, Ayse; Ayla, SuleBackground: The newest NOX isoform, NOX5, has been found in mammalian spermatozoa. Many physiological and pathological situations in spermatozoa are mediated by reactive oxygen species (ROS). NOX5 is the main source of ROS in spermatozoa. Our purpose was to investigate the changes in NOX5 expression and the effect of NOX5 expression on sperm motility, chromatin integrity, and oxidative status in oligoasthenozoospermic compared to normozoospermic men. Methods: Semen samples were collected from 30 normozoospermic (NS) and 30 oligoasthenozoospermic (OAS) men. NOX5 protein expression in sperm samples was evaluated by immunohistochemistry and western blot. Oxidative stress status was evaluated by total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidative stress index (OSI) parameters. Chromatin integrity in spermatozoa was evaluated by toluidine blue staining. Results: NOX5 expression levels were significantly higher in OAS group than in NS group (p<0.001). In addition, chromatin integrity was significantly higher in the OAS group in comparison to NS group (p<0.001). TAC levels were higher in the NS group, but OSI and TOC levels were significantly higher in OAS group (p<0.001). It was found that NOX5 protein expression was positively correlated with oxidative stress and chromatin integrity and negatively correlated with motility (p<0.01). Conclusion: These results suggest that overexpression of NOX5 may be the source of excessive ROS production and oxidative stress injuries in oligoasthenozoospermic men. Considering that NOX5 expression is positively correlated with oxidative stress and chromatin integrity but negatively correlated with motility, it can be considered a biomarker to be used in assisted reproductive procedures. Copyright © 2024, Journal of Reproduction & Infertility.Öğe Comparison of IL-1β, IL-17 and IL-18 levels in the follicular microenvironment in tubal factor and unexplained infertility cases in IVF cycles(İlker ÇAMKERTEN, 2026) Korkmaz, Oya; Karabulut, Seda; Macit, PelinThis study compares follicular fluid (FF) and serum IL-1β, IL-17, and IL-18 levels, as well as total antioxidant (TAC) and total oxidant (TOC) capacities in cases of tubal factor and unexplained infertility, and to investigate the relationship of these parameters with oocyte and embryo quality and clinical pregnancy outcomes. Seventy patients undergoing IVF cycles were divided into two groups: tubal factor (n = 35) and unexplained infertility (n = 35). IL-1β, IL-17, and IL-18 levels in FF and serum samples were measured by ELISA; TAC and TOC were measured spectrophotometrically. Intergroup differences and correlations between biochemical markers and embryological variables were statistically analysed. In the unexplained infertility group, IL-1β, IL-17, IL-18 levels were significantly higher, TAC levels were lower, and TOC and OSI values were increased, particularly in follicular fluid (p < 0.05). No significant differences were found in serum levels. In FF, positive correlations were found between cytokine levels and TOC and OSI, and negative correlations with TAC. In logistic regression analysis, FF IL- 18 (OR = 0.78, p = 0.02) and OSI (OR = 0.82, p = 0.03) were independent factors reducing the likelihood of clinical pregnancy. Cases of unexplained infertility are characterised by follicular microenvironment inflammasome-Th17 activation and redox imbalance. This condition may adversely affect oocyte and embryo quality. Analysis of IL-1β, IL-17, IL-18, TAC, TOC, and OSI levels in FF and serum may guide diagnostic differentiation and targeted treatment strategies. The findings suggest that antioxidant and inflammasome-targeted approaches may be potential adjunctive treatment options in unexplained infertility.
Öğe Distribution of indications for couples undergoing IVF treatment in Türkiye(Istanbul Medipol University, 2026) Karabulut, Seda; Korkmaz, Oya; Yilmaz, Elif; Delikara, NuriInfertility is defined as the failure to conceive after 12 months of regular, unprotected intercourse. Accurate diagnosis requires a detailed history, physical examination, ovarian reserve assessment in women, and semen analysis in men. This study evaluated the distribution of infertility indications among 2.449 couples who underwent IVF treatment at Istanbul Florence Nightingale Hospital between 2013 and 2020. Descriptive statistics and chisquare tests were used to compare infertility indications across age groups and comorbidity categories. Female factor infertility was the most common indication (46.53%), followed by male factor (31.29%), unexplained infertility (16.33%), and combined factor (5.85%). The predominance of female factor infertility is strongly associated with advanced maternal age and age-related declines in reproductive potential. These findings contribute to a clearer understanding of infertility aetiology and can support more targeted clinical management, early fertility assessment, and informed reproductive health policies, particularly for women of advanced reproductive age. © Medipol University Press.Öğe Dose- and size-dependent effects of Fe3O4 nanoparticles on bull sperm cryopreservation(Academic Press Inc Elsevier Science, 2026) Ozturk, Ali Erdem; Dadi, Seyma; Bodu, Mustafa; Korkmaz, Oya; Atay, Yunus Emre; Sariozkan, Serpil; Ocsoy, IsmailFe3O4 nanoparticles (Fe3O4 NPs) are widely used in health sciences, including reproductive biotechnology. In reproductive systems, they have been applied in sperm cryopreservation, nano-purification, drug delivery, and toxicity assessments. However, most studies have evaluated Fe3O4 NPs at only a single size and dose, even though their biological effects may vary with size-dependent characteristics. Therefore, this study aimed to investigate how magnetic Fe3O4 NPs of different sizes and concentrations influence the cryopreservation of bull sperm. Initially Fe3O4 NPs with three sizes (similar to 6, similar to 20, and similar to 80 nm) were synthesized, and two concentrations (10 and 50 mu g/mL) were added to diluted semen samples, supplemented with a commercial extender and cryopreserved. The findings showed that 6 nm Fe3O4 NPs maintained total and progressive motility at levels similar to the control group at both doses, whereas a reduction in both motility parameters was observed only in the Fe20-10 group. No statistically significant differences were found in kinematic parameters, acrosomal, or plasma membrane integrity. Conversely, the 50 mu g/mL doses of the 20 and 80 nm groups decreased mitochondrial membrane potential (MMP). Chromatin condensation improved in all experimental groups compared to the control, which correlates with reduced DNA damage across nanoparticle (NP) treatments. Zeta potential measurements demonstrated that surface charge varied with particle size, and microscopic evaluations revealed the accumulation of positively charged Fe3O4 NPs in the head region. Overall, this study showed that Fe3O4 NPs exhibit distinct size-dependent characteristics, underscoring the importance of preliminary trials to determine the optimal NP size for spermatological applications.Öğe Effects of co-supplementation of trehalose with fetuin and taxifolin in freezing extender on quality parameters of bull spermatozoa following freeze-thaw process(Academic Press Inc Elsevier Science, 2025) Bucak, Mustafa Numan; Taravat, Morteza; Korkmaz, Oya; Soliemanzadeh, Ali; Karimpour, Mojtaba; Maroufi, Mohammad Saber; Topraggaleh, Tohid RezaeiGlycerol is commonly used as a cryoprotectant in bovine sperm cryopreservation; however, its cytotoxic effects can negatively impact sperm quality. This study aimed to reduce glycerol concentration in semen extenders by supplementing with natural antioxidants (taxifolin and fetuin) and the disaccharide trehalose. Twelve ejaculates were collected from three bulls and initially evaluated, then diluted in a tris-egg yolk (TEY) extender containing either 7 % or 4 % glycerol. The control group received 7 % glycerol (TEY), while experimental groups included G7F (TEY + fetuin), G7T (TEY + taxifolin), G7M (TEY + fetuin + taxifolin), and 4 % glycerol groups supplemented with 50 mM trehalose: G4 (TEY + trehalose), G4F (TEY + fetuin), G4T (TEY + taxifolin), and G4M (TEY + fetuin + taxifolin). Post-thaw evaluations included assessments of sperm motility, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential (MMP), DNA fragmentation, and oxidative stress markers. The G4F and G4T groups exhibited significantly higher total and progressive motility, viability, plasma membrane integrity, and MMP compared to other groups (p < 0.05). Furthermore, these groups showed significantly lower malondialdehyde (MDA) levels, indicating reduced lipid peroxidation and oxidative stress (p < 0.05). In conclusion, co-supplementation of 50 mM trehalose with 50 mu M taxifolin and 5 mg/mL fetuin in a cryopreservation extender containing 4 % glycerol may enhance the post-thaw quality of bull spermatozoa.Öğe Erkek Üreme Sisteminde Eksozomların Potansiyel Rolü(Sivas Cumhuriyet Üniversitesi, 2024) Korkmaz, Oya; Bucak, Mustafa Numanİnfertilite hem erkekler de hem de kadınlarda görülebilen bir üreme sistemi bozukluğudur ve küresel bir sağlık sorunu haline gelmiştir. İnfertil vakaların yaklaşık %50'sinin erkek üreme bozukluklarından kaynaklandığı bilinmektedir. Eksozomlar, çok çeşitli hücreler tarafından salgılanan ve semen de dahil olmak üzere biyolojik sıvılarda bol miktarda bulunan nano boyutlu membran vezikülleridir. Lipidler, proteinler, mikroRNA'lar ve mRNA'lar içerirler ve hücre içi iletişimde önemli rol oynadıkları bilinmektedir. Seminal eksozomlar esas olarak epididimozomları ve prostasomları içerir. Yapılan çalışmalar, eksozomların üreme süreçlerini düzenlemede merkezi bir rol oynadığını göstermektedir. Eksozom tedavisinin kullanımı, hastalarda infertilite tedavisinde önemli bir potansiyele sahiptir. Bu membran veziküllerin biyolojik sıvılardaki miktarı, fizyolojik ve patolojik durumlarla bağlantılı olabilir. Seminal plazmanın ve seminal eksozomların moleküler bileşimi, vezikül trafiği ve spermatozoa ile füzyonunu kimin düzenlediği ve sperm fizyolojisindeki eksozomal işlevlerin neler olduğu hala belirsizliğini korumaya devam etmektedir. Bu derleme, eksozomların erkek üreme sistemi üzerindeki etkilerini tartışmaya odaklanmaktadır. Bu konudaki güncel araştırma bulguları analiz edilerek, erkek üreme sağlığı üzerindeki eksozomların katkısı hakkındaki bilgiler vurgulanmaktadır.Öğe Eugenol attenuates paclitaxel-induced cardiotoxicity by modulating autophagy-related markers in rats(Mashhad Univ Med Sciences, 2026) Yildiz, Halime Tozak; Kucukgunay, Sadik; Korkmaz, Oya; Kocak, Seda; Bucak, Mustafa NumanObjective(s): Paclitaxel (PTX) is a commonly used chemotherapeutic agent that causes cardiotoxicity characterized by oxidative stress, inflammation, and mitochondrial dysfunction, which disrupts autophagy and apoptosis in cardiomyocytes. This study investigated the therapeutic potential of eugenol (EUG), a natural anti-oxidant and anti-inflammatory compound, against PTX-induced cardiac damage. Materials and Methods: Thirty-six male Wistar rats were randomly assigned to six groups: Control, EUG5, EUG25, PTX, PTX+EUG5, and PTX+EUG25. Hemodynamic parameters (systolic and diastolic blood pressure and heart rate), serum cardiac biomarkers (troponin T and brain natriuretic peptide), histopathological alterations, and immunohistochemical expression of autophagy-related proteins (mTOR, ULK1, and Atg13) were evaluated. Results: PTX administration significantly reduced arterial blood pressure and increased serum cardiac injury biomarkers, accompanied by marked myocardial structural damage. Histopathological analysis revealed myocardial degeneration, inflammation, edema, and tissue disorganization in the PTX group. In PTX-exposed rats treated with EUG, arterial blood pressure was higher, and serum cardiac injury biomarkers were lower than in the PTX group, accompanied by reduced histopathological scores. PTX exposure was associated with decreased mTOR expression and increased ULK1 and Atg13 immunoreactivity, while EUG-treated PTX groups showed values closer to those of the control group for these autophagy-related markers. Conclusion: EUG administration was associated with reduced biochemical and histopathological indicators of cardiac injury in PTX-exposed rats, along with changes in autophagy-related markers. These findings demonstrate that EUG treatment coincided with attenuation of PTX-induced cardiac injury at the biochemical and histopathological levels, suggesting its potential experimental value in models of chemotherapy-associated cardiotoxicity.Öğe Evaluation of AFP III-Conjugated Fe3O4 Nanoparticles on Bull Sperm Cryopreservation(Wiley, 2025) Ozturk, Ali Erdem; Dadi, Seyma; Bodu, Mustafa; Korkmaz, Oya; Atay, Yunus Emre; Sariozkan, Serpil; Ocsoy, IsmailAntifreeze proteins are naturally occurring proteins that are known for their ability to inhibit ice formation. Although effective in nature, they have failed to produce the expected results in cryobiological studies. However, the lack of a significant effect when used alone has raised the following question: Could conjugation with Fe3O4 nanoparticles (Fe3O4 NPs), which are frequently used in drug delivery studies, enable closer interaction with spermatozoa and provide cumulative protection? To address this question, bull spermatozoa were used. First, Fe3O4 NPs (similar to 6 nm) and AFP III-conjugated Fe3O4 NPs (AFP III@Fe3O4 NPs) were synthesised and characterised by dynamic light scattering, zeta potential analysis, and FTIR spectroscopy to confirm the conjugation. Then, sperm samples collected from five different Holstein bulls for five replications were diluted with AndroMed extender and divided into five groups: control, Fe3O4 NPs only, AFP III only (0.1 and 0.5 mu g/mL), and AFP III@Fe3O4 NPs (0.042 and 0.075 mu g/mL). After cryopreservation, spermatological parameters and DNA condensation were analysed. The AFP III@Fe3O4 NPs (0.075 mu g/mL) exhibited significantly higher motility and DNA integrity compared to the other treatment groups (p < 0.05). However, no statistically significant differences were observed in mitochondrial membrane potential, membrane, and acrosomal integrity. Analyses of motility and DNA damage supported the protective effect of the AFP III@Fe3O4 NPs 0.075 mu g/mL formulation. Thus, we have demonstrated the applicability of AFP III@Fe3O4 NPs, for the first time, in bull sperm cryopreservation and have introduced a novel nano-biotechnological approach for improving the success of assisted reproductive technologies in livestock.Öğe Follicular cytokine profiles and granulosa cell integrity across ovarian response during in vitro fertilisation(Churchill Livingstone, 2026) Korkmaz, Oya; Karabulut, Seda; Macit, PelinBackground: Ovarian response to controlled ovarian stimulation varies considerably among women and may be influenced by inflammatory activity within the follicular microenvironment. Objective: To examine the relationship between ovarian response and follicular inflammatory activity by evaluating IL-1 beta, IL-17, and IL-18 levels, granulosa cell expression, and markers of chromatin integrity and apoptosis in IVF cycles. Methods: A total of 150 women undergoing controlled ovarian stimulation were grouped as low, normal, or high ovarian response (n = 50 each). Follicular fluid cytokine levels were measured by ELISA/CLIA, granulosa cell cytokine expression was assessed immunohistochemically, and chromatin integrity and DNA fragmentation were evaluated using Toluidine Blue and TUNEL assays. Results: Follicular fluid levels and granulosa cell immunopositivity of IL-1 beta, IL-17, and IL-18 increased progressively from low to high ovarian response groups (p < 0.05). Chromatin integrity was best preserved in the normal responder group, whereas both Toluidine Blue-positive and TUNEL-positive granulosa cell ratios were significantly higher in low and high responders (p < 0.01). IL-18 levels showed positive correlations with oocyte number, serum estradiol levels, and MII oocyte ratio (p < 0.05). Notably, granulosa cell IL-18 expression was inversely correlated with DNA fragmentation, suggesting a potential cytoprotective role under physiological inflammatory conditions. Conclusion: These findings demonstrate that follicular cytokine balance is closely associated with ovarian response and granulosa cell integrity during IVF. IL-18 emerges as a key regulator linking physiological inflammation to oocyte competence, highlighting its potential relevance for individualized ovarian stimulation strategies.Öğe Follicular fluid oxidative stress and antioxidant defense in relation to maternal age, ovarian reserve, and in vitro fertilization outcomes(Taylor & Francis Ltd, 2026) Korkmaz, Oya; Karabulut, Seda; Macit, Pelin; Cakici, CagriOxidative stress within the follicular microenvironment plays a critical role in oocyte quality and reproductive outcomes. This prospective study examines the association between follicular fluid redox status, maternal age, ovarian reserve, and clinical outcomes in women undergoing in vitro fertilization. Follicular fluid samples were obtained from women undergoing fresh embryo transfer cycles and analyzed for oxidative damage markers (malondialdehyde (MDA), nitric oxide, ischemia-modified albumin, and sialic acid) and antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiol-disulfide homeostasis). Participants were stratified according to maternal age (<= 35 vs. >35 years), serum estradiol levels on the day of human chorionic gonadotropin trigger (<= 90th vs. >90th percentile), and clinical pregnancy outcome. Anti-M & uuml;llerian hormone (AMH) and follicle-stimulating hormone (FSH) levels were recorded as indicators of ovarian reserve. Women aged >35 years exhibited significantly higher MDA and sialic acid levels, accompanied by reduced antioxidant enzyme activities. Cycles resulting in clinical pregnancy showed lower oxidative stress and higher antioxidant capacity compared with non-pregnant cycles. Malondialdehyde levels correlated positively with age and FSH, while antioxidant parameters correlated positively with AMH and pregnancy outcome. Receiver operating characteristic analysis demonstrated moderate discriminative ability of MDA, SOD, CAT, and GSH for clinical pregnancy. These findings indicate that age-related redox imbalance in follicular fluid is associated with diminished ovarian reserve and reduced in vitro fertilization success. Assessment of follicular fluid oxidative stress parameters may provide clinically relevant insights into female reproductive potential.Öğe Impact of Fucoidan on Methotrexate-Induced Oxidative and Apoptotic Responses in Ishikawa Endometrial Cancer Cells(Sivas Cumhuriyet Üniversitesi, 2026) Korkmaz, OyaMethotrexate (MTX) primarily kills tumor cells through its antifolate activity, but emerging evidence shows that its cytotoxicity also involves disruption of cellular redox homeostasis and activation of apoptosis pathways. The use of antioxidant supplements during chemotherapy remains controversial, as they may modulate reactive oxygen species (ROS) levels and thereby influence treatment-related cellular damage. This study explored the effects of fucoidan on MTX-induced redox imbalance and apoptosis-related gene expression changes in ER-positive Ishikawa endometrial carcinoma cells. Experimental groups received MTX, fucoidan, or co-treatment for 24 and 48 hour incubation periods. The MTX IC₅₀ was determined using the MTT viability assay, and a sub-IC₅₀ concentration was selected for combination experiments. Cellular viability was assessed via MTT, oxidative membrane damage was evaluated by measuring malondialdehyde (MDA) levels, and at 24 hours, mRNA levels of Bax and Bcl-2 was quantified by qRT-PCR to calculate the Bax/Bcl-2 ratio as an indicator of mitochondrial apoptotic balance. MTX treatment significantly lower cell viability at both 24 and 48 hours and markedly elevated MDA concentrations compared to controls (p < 0.001). It also strongly upregulated Bax, downregulated Bcl-2, and increased the Bax/Bcl-2 ratio (p < 0.001), reflecting a shift toward pro-apoptotic signaling. Fucoidan alone caused no significant changes in viability, lipid peroxidation, or apoptotic gene expression. However, co-administration of fucoidan with MTX significantly reduced the MTX-induced rise in MDA levels and partially attenuated the rise in the Bax/Bcl-2 ratio relative to MTX alone (p < 0.05). These results demonstrate that MTX disrupts redox balance and promotes mitochondrial apoptosis in Ishikawa cells. Fucoidan partially mitigates MTX-triggered oxidative stress and apoptosis-related transcriptional changes without fully abolishing the drug's cytotoxic effects. This suggests that concurrent antioxidant use can modulate chemotherapy-associated cellular stress responses, emphasizing the need for careful evaluation of antioxidant supplementation during anticancer treatment.Öğe Impact of Maternal Age on the Repairing Capacity of Oocytes on Paternal DNA Damage(Springer Heidelberg, 2025) Karabulut, Seda; Kutlu, Pelin; Korkmaz, Oya; Oria, LimaSperm DNA fragmentation is a primary cause of male infertility, affecting ART outcomes and success rates. Sperm has no DNA repair mechanisms because it is transcriptionally quiet. Oocytes' repairing capacity is one of the suggested methods to overcome the situation. However, based on the hypothesis that oocyte age may also have an impact on this talent, we aimed to reveal the role of female age in repairing sperm DNA damage in our study. A total of 540 couples undergoing ICSI were grouped based on the maternal age, and the groups were further divided into two groups based on the severity of DNA damage rates, as the low (< 30% SDF) and high DNA fragmentation (>= 30% SDF). Laboratory and clinical outcomes were compared between the groups. No significant differences were observed in younger patients (<= 36 y) and patients between 37-40 years. However, when maternal age was > 40, significantly lower embryo and blastocyst quality, blastocyst development, pregnancy, and implantation rates were observed. Our findings suggest that older oocytes may have a reduced ability to repair sperm DNA damage, as demonstrated by poorer IVF outcomes of couples with higher SDF scores and advanced maternal age (>= 40).Öğe Molecular Extremes of Ovarian Response: Divergent PI3K/AKT/mTOR Signaling and Oxidative Stress Patterns in Low and High Responders Undergoing In Vitro Fertilization(Wiley, 2026) Korkmaz, Oya; Karabulut, Seda; Macit, Pelin; Keskin, IlknurOvarian response extremes are associated with distinct alterations in the follicular microenvironment, yet the underlying molecular mechanisms remain incompletely understood. This study investigated oxidative stress, antioxidant responses, apoptosis, and PI3K/AKT/mTOR signaling in granulosa cells from women undergoing intracytoplasmic sperm injection, stratified into poor (POR), normal (NOR), and high ovarian response (HOR) groups (n = 30). Follicular fluid oxidative stress markers, antioxidant systems, and regulatory factors were analyzed, while intracellular reactive oxygen species, DNA fragmentation, and chromatin integrity were evaluated in granulosa cells. In addition, PI3K/AKT/mTOR pathway activity was assessed using immunohistochemistry and immunofluorescence. Compared with NOR, both POR and HOR groups exhibited increased oxidative stress, reflected by elevated MDA levels (p < 0.05), accompanied by divergent antioxidant responses, including reduced GSH levels in POR and a progressive increase in SOD activity from NOR to HOR (p < 0.05). Although melatonin and TGF-beta levels did not differ significantly, melatonin showed a trend toward lower levels in POR and higher levels in HOR. Granulosa cell ROS production and apoptosis-related markers were significantly increased in both response extremes, particularly in POR (p < 0.05). Consistently, PI3K/AKT/mTOR signaling displayed differential regulation, with reduced activation in POR and enhanced activation in HOR compared to NOR (p < 0.05). Overall, NOR appears to reflect a balanced redox and molecular state, whereas both poor and high responses are characterized by oxidative stress, cellular damage, and dysregulated PI3K/AKT/mTOR signaling. These findings suggest that deviation from physiological equilibrium, rather than response magnitude alone, is a key determinant of granulosa cell dysfunction and impaired follicular competence.Öğe Protective effects of rutin against docetaxel-induced testicular damage in rats: Effects on antioxidant defence, apoptosis and autophagy(Pergamon-Elsevier Science Ltd, 2026) Kucukgunay, Sadik; Yildiz, Halime Tozak; Korkmaz, Oya; Bolacali, Memis; Bucak, Mustafa Numan; Cay, Hasan Ali; Guler, SohretDocetaxel (DTX), a widely used chemotherapeutic agent, is known for its effectiveness in cancer treatment but also for its toxic effects on healthy tissues, particularly the male reproductive system. This study aimed to investigate the protective role of rutin, a natural flavonoid with known antioxidant and anti-apoptotic properties, against DTX-induced testicular damage in rats. Thirty-six adult male Wistar rats were randomly divided into six groups: Control, Rutin 50 mg/kg (R50), Rutin 100 mg/kg (R100), DTX, DTX+R50, and DTX+R100. A single dose of DTX (30 mg/kg, i.p.) was administered, while rutin was given orally for 7 days. On day eight, all animals were sacrificed. Sperm parameters (concentration, motility, morphology, chromatin integrity), serum testosterone and inhibin B levels, and testicular MDA and SOD levels were assessed. Histological evaluations were conducted using hematoxylin-eosin staining, Johnsen scoring, and tubule diameter measurements. Immunohistochemical analysis of Caspase-3, Bax, Bcl-2, mTOR, ULK1, and Atg13 was performed. Data were analyzed, and p < 0.05 was considered statistically significant. DTX significantly impaired sperm motility and hormone levels, increased oxidative stress, and caused histological damage in the testes (p < 0.001). Rutin, especially at 100 mg/kg, ameliorated these effects, restoring sperm function, hormonal balance, and testicular architecture. Furthermore, rutin reduced DTX-induced apoptosis and autophagy marker expression while preserving Bcl-2 levels (p < 0.001). DTX induces structural and functional impairments in testicular tissue via oxidative stress, apoptosis, and autophagy. Rutin demonstrated a dose-dependent protective effect, suggesting its potential as a supportive agent against chemotherapy-induced gonadotoxicity.Öğe Resveratrol, Ishikawa Endometriyal Kanser Hücrelerinde Apoptoz ve Hücre Döngüsü ile İlişkili Gen Ekspresyonunu Modüle Eder(Dicle Üniversitesi, 2026) Korkmaz, OyaGiriş: Bu çalışma, ER-pozitif endometriyal kanser hücre hattı Ishikawa’da resveratrolün hücre canlılığı, apoptoz, proliferasyon ve östrojen reseptörü/PTEN ile ilişkili yolaklar üzerindeki etkilerini incelemeyi amaçlamıştır. Yöntemler: Ishikawa hücrelerine farklı konsantrasyonlarda resveratrol uygulanmış ve hücre canlılığı 24, 48 ve 72 saatlerde MTT testi ile değerlendirilmiştir. Doz–yanıt sonuçlarına dayanarak moleküler analizler için sub-sitotoksik dozlar (15 ve 30 μM) seçilmiştir. Apoptoz ile ilişkili genlerin (BAX, BCL-2, CASP3), proliferasyon belirteci CCND1’in, östrojen reseptör geni ESR1’in ve tümör baskılayıcı PTEN’in mRNA ekspresyon düzeyleri qRT-PCR yöntemi kullanılarak kantitatif olarak belirlenmiştir. Bulgular: Resveratrol uygulaması Ishikawa hücre canlılığında doza ve zamana bağlı, progresif bir azalmaya yol açmıştır. qRT-PCR analizleri, pro-apoptotik BAX ve CASP3 genlerinde artış; anti-apoptotik BCL-2 ve proliferasyonla ilişkili CCND1 genlerinde azalma; ESR1 ekspresyonunda belirgin baskılanma ve PTEN ekspresyonunda doza bağlı artış olduğunu göstermiştir. Artmış BAX/BCL-2 oranı, hücresel dengenin pro-apoptotik yönde değiştiğini göstermektedir. Sonuç: Bu bulgular, resveratrolün pro-apoptotik transkripsiyonel yanıtları desteklediğini ve hücre canlılığını azalttığını; bu etkilerin östrojen reseptörü sinyallemesi ve PTEN ile ilişkili genlerde meydana gelen değişikliklerle ilişkili olabileceğini göstermektedir. Sub-sitotoksik konsantrasyonlarda gözlenen etkiler, resveratrolün ER-pozitif endometriyal kanser modellerinde deneysel adjuvan tedavi için umut verici bir aday olabileceğini düşündürmektedir.Öğe Size-dependent cryoprotective effects of curcumin nanoparticles on DNA integrity and motility in cryopreserved Angora buck sperm(Frontiers Media Sa, 2026) Ozturk, Ali Erdem; Sariozkan, Serpil; Bodu, Mustafa; Atay, Yunus Emre; Sahin, Derya; Korkmaz, Oya; Ocsoy, IsmailCurcumin is a potent antioxidant and anti-inflammatory agent derived from the Curcuma longa plant. However, its low water solubility and limited bioavailability restrict its effectiveness in cryopreservation applications. In this study, curcumin nanoparticles (CNp) were produced in two different sizes (20 and 80 nm) to increase bioavailability, and their effects on the freezing of Angora buck sperm were investigated. Semen was collected a total of six times from five Angora bucks (aged 2-3 years). The collected semen was pooled in equal volumes, diluted with a Tris-based egg yolk diluent, and distributed among the experimental groups. Experimental groups set as: control, CNp 20-1 (20 nm CNp at 1 mu g/ml), CNp 20-5 (20 nm CNp at 5 mu g/ml), CNp 80-1 (80 nm CNp at 1 mu g/ml), and CNp 80-5 (80 nm CNp at 5 mu g/ml), and were drawn into 0.25 ml straws and frozen. After thawing, motility, kinematic parameters, plasma membrane and acrosomal integrity (PMAI), mitochondrial membrane potential (MMP), and DNA integrity analyses were performed. The highest motility value was observed in the CNp 20-1 group (p < 0.05), but the groups containing 80 nm CNp reduced MMP (p < 0.01). There was no statistical difference between groups in PMAI. DNA integrity remained within acceptable limits in all groups and was better preserved compared to the control group (p < 0.05). In addition to these findings, dynamic light scattering (DLS) analyses revealed that CNps exhibited increased water-absorbing capacity and aggregation. The hydrodynamic diameters of 20 and 80 nm CNps were found to be 223.3 and 289.3 nm, respectively. The findings indicate that the size of curcumin nanoparticles significantly affects aggregation behavior, motility, and DNA integrity parameters. These results suggest that curcumin nanoparticles with a 20 nm size may offer a more effective strategy for the cryopreservation of Angora buck sperm.Öğe The Association Between Mature Oocyte Proportion and IVF Success: A Retrospective Analysis of 2,565 ICSI Cycles(Avicenna Research Institute, 2025) Korkmaz, Oya; Karabulut, Seda; Yılmaz, Elif; Delikara, NuriBackground: IVF/ICSI success depends on the proportion of fertilizable metaphase II (MII) oocytes, yet direct evidence linking mature-oocyte rate to clinical outcomes remains limited. This study aimed to assess the impact of mature oocyte rate on clinical pregnancy outcomes in a large retrospective cohort of women undergoing ICSI. Methods: A total of 2,565 women who underwent ICSI cycles at a single IVF center in Türkiye were retrospectively analyzed. Patients were stratified into three groups according to mature oocyte proportion: Group 1 (0-50%), Group 2 (51-75%), and Group 3 (76-100%). Data were analyzed per initiated ICSI cycle. Embryo transfer was performed on day 3 or day 5 post-fertilization, depending on embryo quality and patient characteristics. Logistic regression analysis was performed to assess the independent effect of mature oocyte rate on pregnancy outcomes. Statistical significance was set at p<0.05. Results: Clinical pregnancy rates were significantly lower in Group 1 (10.23%) compared to Group 2 (28.96%) and Group 3 (29.99%) (p<0.001). Live birth and implantation rates increased in the higher maturity groups (7.5% vs. 21.5% vs. 22.9% and 12.1% vs. 24.3% vs. 26.0%, respectively), whereas miscarriage rates decreased (18.9% vs. 13.4% vs. 12.8%). Logistic regression analysis confirmed that a higher mature oocyte proportion was an independent predictor of clinical preg-nancy (Group 2: OR=3.4, 95%CI: 2.5-4.6; Group 3: OR=3.5, 95%CI: 2.6-4.7; p<0.001). Conclusion: This large-scale retrospective cohort analysis demonstrates that mature oocyte proportion is an important prognostic factor of IVF success. Mature oocyte proportion should be considered an essential parameter in clinical practice and patient counseling. © 2025, Journal of Reproduction & Infertility.Öğe The Blood-Follicle Barrier(Nova Science Publishers, Inc., 2025) Korkmaz, OyaOocyte and granulosa cells engage in tight and intricate communication during the process of follicular formation. Insufficient signalling between these two cell types leads to infertility. Follicular fluid is an intricate fluid that makes up the environment in which follicles form. It contains substances generated by the surrounding cells and compounds from the blood plasma that pass over the blood-follicle barrier (BFB). The BFB is a type of blood-tissue barrier found throughout the mammalian body and serves to maintain the balance of the oocyte environment by separating blood from follicular fluid. The BFB functions as a molecular sieve, selectively allowing molecules to pass through based on their size and charge within the ovarian follicles. The BFB is primarily formed by the tight junction-permeability barrier of the endothelial cells in the microvessels surrounding the developing follicle. Additionally, the basement membrane of the developing follicle plays a significant role in the BFB by undergoing rapid changes in its composition during follicle development. The pharmacodynamics of the BFB are intricate, and there is difficulty in overcoming physiological barriers that impact different local and systemic methods of delivery. Although the BFB and its ultrastructure were explained over sixty years ago, there are few reports in the literature that specifically explore the biology, regulation, and function of the BFB in both healthy and diseased states. The objective of this chapter is to offer the latest information on the crucial BFB. To improve ovarian function, it is important to comprehensively understand the blood follicle barrier and to investigate this area further. © 2025 Nova Science Publishers, Inc. All rights reserved.Öğe The Effects of Graphene Oxide Nanoparticles on the Cryopreservation of Angora Buck Sperm(Mdpi, 2026) Ozturk, Ali Erdem; Bodu, Mustafa; Atay, Yunus Emre; Sariozkan, Serpil; Sahin, Derya; Korkmaz, Oya; Hitit, MustafaNano-graphene oxide (NGO) is a nanomaterial that has been frequently used in the fields of health and bioengineering in recent years. However, its potential use in semen cryopreservation is still in the exploratory phase. In this study, Angora bucks, a breed with low resistance to cold shock, were used. Sperm was collected from five different Angora bucks, pooled, diluted with a Tris-based egg yolk diluent, and frozen with the addition of NGO at two different sizes (50 and 500 nm) and doses (10 and 50 & micro;g/mL). Nanoparticle characterization was performed using field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR). Post-thaw sperm analyses were evaluated based on motility and kinematic parameters, mitochondrial membrane potential (MMP), plasma membrane and acrosome integrity (PMAI), and DNA fragmentation. Applying 50 nm NGO at a dose of 50 & micro;g/mL led to statistically significant improvements in motility and PMAI (p < 0.05). The same dose of 500 nm NGO, however, only showed a statistically significant improvement in the PMAI parameter (p < 0.05). No significant differences were observed between the groups for MMP and kinematic parameters (p > 0.05). Conversely, it was found that all sizes and doses of NGO significantly protected post-thaw sperm regarding DNA integrity (p < 0.05). These findings indicate that the NGO, at a size of 50 nm and a dose of 50 & micro;g/mL, improves the post-thaw quality of Angora buck sperm and provides a cryoprotective effect that depends on size and dose. This study provides preliminary data on the potential effects of NGO; however, comprehensive mechanistic and in vivo validation studies are required to establish the biological and clinical validity of these findings.
