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16 pages, 1743 KB  
Review
Robotic-Assisted MicroTESE: A Scoping Review of Current Evidence and Future Perspectives
by Lucio Dell’Atti
Reprod. Med. 2026, 7(4), 56; https://doi.org/10.3390/reprodmed7040056 - 8 Oct 2026
Abstract
Background/Objectives: Robotic-assisted microsurgery has progressively been adopted in andrology, extending from vasectomy reversal and subinguinal varicocelectomy to more exploratory applications such as robotic-assisted microdissection testicular sperm extraction (RA-microTESE) for men with non-obstructive azoospermia (NOA). RA-microTESE has been proposed to combine the established [...] Read more.
Background/Objectives: Robotic-assisted microsurgery has progressively been adopted in andrology, extending from vasectomy reversal and subinguinal varicocelectomy to more exploratory applications such as robotic-assisted microdissection testicular sperm extraction (RA-microTESE) for men with non-obstructive azoospermia (NOA). RA-microTESE has been proposed to combine the established benefits of standard microscopic microTESE with the ergonomic and optical advantages of robotic platforms, including tremor elimination, stereoscopic three-dimensional visualisation, and multi-instrument articulation. The clinical evidence supporting this specific application, however, has never been systematically mapped. Methods: A scoping review was conducted following the PRISMA extension for Scoping Reviews (PRISMA-ScR) framework. PubMed/MEDLINE, Scopus, Web of Science and Google Scholar were searched from inception to July 2026 for sources addressing robotic-assisted microTESE, using combinations of “robot*”, “da Vinci”, “microTESE” and “testicular sperm extraction”. Original studies, case reports/series, and narrative or systematic reviews with a dedicated section on robotic microTESE were eligible; the diagnostic pathway leading to patient selection for microTESE—hormonal, genetic, histological and imaging-based predictors of sperm retrieval—was mapped separately through a targeted, purposive literature search across six predefined diagnostic domains. Results: Five sources met the inclusion criteria for robotic-assisted microTESE. Only one original clinical experience—a single-institution series of 12 robot-assisted microTESE procedures—has been reported, described across several overlapping publications, with no quantified sperm retrieval rate (SRR), operative time, or complication rate, and no comparative or randomised data against conventional microTESE. The diagnostic mapping showed that the work-up of NOA relies on an increasingly sophisticated combination of hormonal biomarkers (FSH, inhibin B, anti-Müllerian hormone), genetic testing (karyotype, Y-chromosome microdeletion), seminal molecular/proteomic markers (e.g., TEX101, ECM1), imaging (Doppler and contrast-enhanced ultrasound), artificial-intelligence/machine-learning prediction models, and testicular histopathology to predict SRR; all of these tools have been developed in conventional microTESE cohorts and none has yet been integrated into any robotic platform. Conclusions: RA-microTESE remains a technically feasible but clinically unproven adjunct to standard microTESE. Existing evidence is limited to descriptive reports from a single pioneering group, precluding conclusions on superiority, equivalence, or cost-effectiveness relative to microscope-based microTESE. The lack of integration between validated diagnostic predictors of sperm retrieval and robotic surgical platforms represents a concrete, currently unexploited research opportunity at the intersection of robotics and diagnostics in male infertility care. Full article
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21 pages, 4966 KB  
Article
Molecular Characterization and Functional Analysis of Pomacea canaliculata Mos Gene (PcMos): A Molecular Switch of Female Fecundity
by Haotian Gu, Haiyuan Teng, Tianshu Zhang and Yongda Yuan
Biology 2026, 15(19), 1774; https://doi.org/10.3390/biology15191774 - 6 Oct 2026
Viewed by 52
Abstract
The invasive Pomacea canaliculata has emerged as a notorious pest that endangers aquatic crops, ecological services and functioning. Although well-documented as a mammalian oocyte maturation factor, the biological roles of Moloney sarcoma oncogene (Mos) in invertebrates, notably P. canaliculata, remain [...] Read more.
The invasive Pomacea canaliculata has emerged as a notorious pest that endangers aquatic crops, ecological services and functioning. Although well-documented as a mammalian oocyte maturation factor, the biological roles of Moloney sarcoma oncogene (Mos) in invertebrates, notably P. canaliculata, remain unfathomed. We integrated RNA interference (RNAi)-mediated gene silencing alongside bioinformatic, molecular, biochemical and histological approaches to dissect fecundity-related functions and modulatory mechanisms of PcMos at the mRNA, protein and in silico levels. Characterized by the conserved protein kinase domain and motif, the PcMos protein sequence presented close phylogeny with its molluscan counterparts. Spatiotemporal expression profiling showed that mRNA and protein levels of PcMos were enriched in female adults and ovarian tissues. Efficient in vivo RNAi effects were induced as the transcription and translation of PcMos significantly declined by 78.2% and 79.0%, respectively, following a microinjection of 5 μg dsPcMos per female post 48 h. The downstream MAPK pathway, comprising MEK1, ERK1 and p90RSK1, was depressed when subjected to dsPcMos treatment, as reflected by pronounced decreases in mRNA and phosphorylated protein levels. Substantial diminution of E2/Pg/LH/FSH contents were noticed in the PcMos-RNAi group versus the dsEGFP group, suggesting fundamental implications of PcMos in endocrine regulation. In addition, the concurrent expression and high affinity between PcMos and VTG were visualized by the immunofluorescence and molecular docking, which may be associated with the diminished VTG content and expression upon PcMos silencing. Moreover, PcMos knockdown led to impaired ovarian development and reduced SP content, the number ofmature oocytes, egg production and egg-hatching rates. Taken together, our findings pointed to PcMos as a molecular switch pivotal for female fecundity, potentially acting through coordinated effects on MAPK signaling, endocrine hormone homeostasis and yolk deposition. This study may inspire the precision pest management and inform the design of RNAi-based sterility agents to suppress P. canaliculata populations. Full article
(This article belongs to the Special Issue Biological Invasions in Freshwater Ecosystems)
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27 pages, 1752 KB  
Systematic Review
The Therapeutic Potential of Berry-Derived and Berry-Based Interventions in Inflammatory Bowel Disease: A Comprehensive Systematic Review of Preclinical and Clinical Evidence
by Lucia Carmela Passacatini, Rosamaria Caminiti, Valeria Mazza, Saverio Nucera, Stefania Proietti, Francesca Oppedisano, Jessica Maiuolo, Roberta Macrì, Maria Serra, Valentina Malafoglia, Federica Marrelli, Andrea Soluri, Myriam Carpenito, Carlo Tomino, Vincenzo Mollace, Sara Ilari and Carolina Muscoli
Nutrients 2026, 18(19), 3280; https://doi.org/10.3390/nu18193280 - 6 Oct 2026
Viewed by 74
Abstract
Introduction: Berry-derived and berry-based interventions have gained increasing attention for their potential health benefits. Berries are rich in diverse bioactive compounds, including polyphenols and anthocyanins, which are associated with a broad range of biological activities, particularly antioxidant and anti-inflammatory effects. Over the last [...] Read more.
Introduction: Berry-derived and berry-based interventions have gained increasing attention for their potential health benefits. Berries are rich in diverse bioactive compounds, including polyphenols and anthocyanins, which are associated with a broad range of biological activities, particularly antioxidant and anti-inflammatory effects. Over the last decade, numerous studies have focused on berries, particularly those from the Ericaceae family (blueberry, cranberry and bilberry), the Solanaceae family (goji berry, Solanum nigrum berries) and the Elaeocarpaceae family (maqui berry). Berries are considered among the best dietary sources of bioactive compounds (BACs). Among chronic gastrointestinal disorders, inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC), both chronic inflammatory conditions of the gastrointestinal tract. The multifactorial nature of IBD significantly impairs quality of life and makes disease management particularly challenging, increasing interest in complementary approaches, in addition to pharmacological treatments, such as phytotherapeutic strategies based on plant-derived bioactive compounds and, in particular, berry-derived and berry-based interventions. Methods: A systematic literature search was conducted using PubMed, Web of Science, and Scopus databases. Specific inclusion and exclusion criteria were applied to identify relevant articles published up to July 2026. After the removal of duplicates and a thorough screening of titles, abstracts, and full texts, a total of 19 studies were included, comprising 16 studies conducted on animal models and 3 clinical studies involving patients. The 3 clinical studies corresponded to 5 publications and involved a total of 68 unique participants, as two publications were secondary analyses of the same patient cohorts. These investigations evaluated the possible effects of berry-derived and berry-based interventions in both experimental models and clinical settings. Results: Preclinical studies suggested potential protective effects against intestinal inflammation by reducing pro-inflammatory cytokines, improving epithelial barrier integrity, and restoring gut microbiota composition. The included clinical studies reported improvements in disease activity, fecal calprotectin levels, quality of life, and remission rates in patients with ulcerative colitis. Nevertheless, the available clinical evidence remains limited and heterogeneous, preventing definitive conclusions regarding clinical efficacy. Conclusions: The current clinical data should therefore be considered preliminary. Larger and more rigorous randomized controlled trials are needed to determine whether the biological effects observed in preclinical models translate into clinically relevant benefits in patients with IBD. Overall, preclinical evidence complements clinical findings by providing mechanistic insights that help contextualize and interpret outcomes observed in human studies. Full article
(This article belongs to the Section Nutritional Immunology)
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13 pages, 512 KB  
Article
The Use of the Drospirenone 4 mg-Only Pill in Overweight and Obese Women with Polyendocrine Metabolic Ovarian Syndrome: A Retrospective Cohort Study
by Klara Hofer, Selina Ebner, Rodrig Marculescu, Magdalena Boegl, Peter Frigo, Robert Krysiak and Johannes Ott
J. Clin. Med. 2026, 15(19), 7701; https://doi.org/10.3390/jcm15197701 - 5 Oct 2026
Viewed by 162
Abstract
Objective: Polycystic ovary syndrome is frequently associated with hyperandrogenemia-related hirsutism, which creates notable cosmetic concerns for many affected women. Although multiple antiandrogenic treatments exist, many patients remain dissatisfied, and combined oral contraceptives are often contraindicated due to metabolic and cardiovascular risk factors. [...] Read more.
Objective: Polycystic ovary syndrome is frequently associated with hyperandrogenemia-related hirsutism, which creates notable cosmetic concerns for many affected women. Although multiple antiandrogenic treatments exist, many patients remain dissatisfied, and combined oral contraceptives are often contraindicated due to metabolic and cardiovascular risk factors. This study evaluates whether a drospirenone-only pill improves hormonal profiles and hirsutism in PMOS compared to cyclic dydrogesterone. Methods: This retrospective cohort study assessed hyperandrogenemia and hirsutism using the modified Ferriman–Gallwey score in 60 overweight or obese women with PMOS who were treated at the Clinical Division of Gynecologic Endocrinology and Reproductive Medicine of the Medical University of Vienna, Austria. Patients underwent follow-up examinations after three and six months of treatment. Thirty women chose treatment with drospirenone-only and were age-matched with 30 women receiving cyclic dydrogesterone. Results: After 3 months, women in the drospirenone group showed significant improvements, including reductions in LH (p < 0.001), FSH (p < 0.001), testosterone (p = 0.001), FAI (p < 0.001) and AMH (p = 0.005). Ferriman–Gallwey scores were significantly lower after 3 months (p < 0.001) and 6 months (p = 0.001). At follow-up, the drospirenone group exhibited lower LH (5.4 vs. 8.8 mIU/mL; p = 0.004) and lower FAI (2.9 vs. 4.0; p = 0.045) compared with controls. Among women with baseline hirsutism (FGS ≥ 8), scores decreased from 14 to 12 (p < 0.001) after 3 months and to 10 (p = 0.002) after 6 months in the drospirenone group. Conclusions: Drospirenone-only treatment resulted in a modest reduction in Ferriman–Gallwey score, with more pronounced improvements observed in women with baseline hirsutism. This was accompanied by hormonal changes, suggesting a potentially beneficial option for women with hyperandrogenic PMOS for whom combined oral contraceptives are not suitable. Full article
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27 pages, 15555 KB  
Article
Effects of Chronic Paroxetine Exposure and Irisin Treatment on Sexual Motivation, Reproductive Endocrine Profile, and Vaginal Histological and Immune-Inflammatory Outcomes in Adult Female Rats
by Ahmet Yardimci, Tugrul Ertugrul, Nazife Ulker Ertugrul and Sinan Canpolat
Biology 2026, 15(19), 1767; https://doi.org/10.3390/biology15191767 - 4 Oct 2026
Viewed by 145
Abstract
Selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, are frequently associated with sexual dysfunction, yet their effects on female reproductive endocrine regulation and the local vaginal tissue environment remain incompletely characterized. Irisin is an exercise-responsive adipomyokine with reported reproductive and immunomodulatory actions, but its [...] Read more.
Selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, are frequently associated with sexual dysfunction, yet their effects on female reproductive endocrine regulation and the local vaginal tissue environment remain incompletely characterized. Irisin is an exercise-responsive adipomyokine with reported reproductive and immunomodulatory actions, but its influence during chronic paroxetine exposure is unknown. This study evaluated the behavioral, endocrine, histological, and immune-related effects of chronic paroxetine treatment and examined whether irisin changed responses. Forty regularly cycling female Sprague–Dawley rats were allocated to sham control, paroxetine, irisin, or paroxetine + irisin groups (n = 10/group). Paroxetine was administered orally at 20 mg/kg/day for 8 weeks, while irisin was delivered continuously by subcutaneous mini-osmotic pumps at 100 ng/kg/day during the final 4 weeks. Sexual incentive motivation and active investigation behaviors, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and anti-Müllerian hormone (AMH), vaginal fibroblast and plasma cell numbers, Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) immunoreactivity, and periodic acid–Schiff (PAS) reactivity were evaluated. Paroxetine did not significantly affect sexual incentive motivation parameters or circulating reproductive hormone concentrations (p > 0.05), but both paroxetine-treated groups showed a lower duration of investigation directed toward the female and a higher male investigation preference ratio than the sham control (p < 0.05). Irisin alone reduced locomotor activity (p < 0.01). Paroxetine increased vaginal fibroblast counts (p = 0.0001) and NF-κB immunoreactivity (p = 0.003) compared with the sham control, whereas TLR4 immunoreactivity remained unchanged. Plasma cell counts were elevated in all treatment groups compared with the sham control (p < 0.0001). Irisin co-treatment reduced fibroblast counts relative to paroxetine group and reduced plasma cell counts relative to both single-treatment groups (all p < 0.001). Vaginal epithelial PAS reactivity was severe (+++) in sham control, weak (+) after paroxetine, and moderate (++) in both irisin-treated groups. Overall, chronic paroxetine exposure produced selective behavioral and local vaginal stromal, immune-inflammatory, and epithelial alterations without significant changes in the measured reproductive hormonal profile. Irisin influenced several vaginal tissue responses but did not change the paroxetine-associated alterations in active investigation behavior. Full article
(This article belongs to the Section Developmental and Reproductive Biology)
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32 pages, 624 KB  
Review
CARTPT and FSH Signaling in Ovarian Follicle Development as an Emerging Link to Oocyte Quality and Female Infertility
by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Diamantis Athanasiou, Antonia Athanasiou, Aikaterini Athanasiou, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis
Curr. Issues Mol. Biol. 2026, 48(10), 1024; https://doi.org/10.3390/cimb48101024 - 3 Oct 2026
Viewed by 91
Abstract
Not all ovarian follicles respond to follicle-stimulating hormone (FSH) in the same way. This difference is usually attributed to FSH receptor expression and local ovarian factors, but the role of CARTPT has received far less attention. Studies in granulosa cells have shown that [...] Read more.
Not all ovarian follicles respond to follicle-stimulating hormone (FSH) in the same way. This difference is usually attributed to FSH receptor expression and local ovarian factors, but the role of CARTPT has received far less attention. Studies in granulosa cells have shown that cocaine- and amphetamine-regulated transcript (CART) can reduce FSH-induced cAMP production, aromatase expression, and estradiol synthesis. CARTPT expression has also been found to be higher in subordinate and atretic follicles in several animal models. Its regulation by leptin suggests a possible connection between metabolic status and follicular function. Early human findings have linked follicular CART expression with ovarian response and oocyte yield. In cattle and buffalo, CART suppressed FSH-stimulated cAMP production, aromatase expression, and estradiol output in granulosa cells and marked follicles destined for atresia, a pattern not confirmed in the one available porcine study. The receptor mediating these effects in the ovary remains unidentified, though a CART receptor was recently confirmed in another endocrine tissue. Human evidence linking CARTPT to ovarian response and oocyte quality remains preliminary and correlative. CARTPT therefore emerges as a mechanistically well-supported but clinically unproven contributor to FSH resistance and impaired oocyte quality, and this review outlines the loss-of-function and prospective human studies needed to establish its clinical relevance. Full article
(This article belongs to the Special Issue Hormonal Regulation in Developmental Biology)
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12 pages, 1371 KB  
Article
Association Between High-Risk Human Papillomavirus Positivity and Ovarian Reserve Markers in Women with Unexplained Oligomenorrhea: A Retrospective Comparative Study
by Ertugrul Sen
Life 2026, 16(10), 1642; https://doi.org/10.3390/life16101642 - 30 Sep 2026
Viewed by 132
Abstract
Aim: to evaluate the association between high-risk human papillomavirus (HR-HPV) positivity and ovarian reserve markers, particularly the anti-Müllerian hormone (AMH), in reproductive-age women presenting with unexplained oligomenorrhea. Methods: this single-center retrospective comparative study included women aged 25–35 years with unexplained oligomenorrhea, categorized into [...] Read more.
Aim: to evaluate the association between high-risk human papillomavirus (HR-HPV) positivity and ovarian reserve markers, particularly the anti-Müllerian hormone (AMH), in reproductive-age women presenting with unexplained oligomenorrhea. Methods: this single-center retrospective comparative study included women aged 25–35 years with unexplained oligomenorrhea, categorized into an HR-HPV-positive group (n = 257) and an HPV-negative control group (n = 1164). Ovarian reserve was assessed using serum AMH, basal follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and antral follicle count (AFC), with AMH measured irrespective of cycle day and other hormones on cycle days 2–5, while AFC was determined by transvaginal ultrasonography. Clinical and lifestyle variables were recorded, and multivariable logistic regression was used to identify factors independently associated with low AMH (<0.5 ng/mL). Results: the groups were comparable in age, body mass index, and parity. AMH was lower in HR-HPV-positive women than in controls (median 2.2 [IQR 1.0–3.8] vs. 2.7 [1.5–4.4] ng/mL; p < 0.001), as was AFC (10 [8–13] vs. 11 [9–14]; p < 0.001); the absolute differences were small (Cohen’s d ≤ 0.19). Low AMH was approximately twofold more frequent among HR-HPV-positive women (11.7% vs. 6.3%), and age (OR 1.36, 95% CI 1.26–1.47) and HR-HPV positivity (OR 2.07, 95% CI 1.24–3.47) were independently associated with low AMH; the association persisted at an alternative threshold of <1.1 ng/mL (adjusted OR 2.25, 95% CI 1.57–3.23). Conclusion: HR-HPV positivity was associated with lower AMH and AFC values in women with unexplained oligomenorrhea. These findings indicate a group-level association rather than a causal relationship and require confirmation in prospective studies incorporating HPV persistence and reproductive outcomes. Full article
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18 pages, 2795 KB  
Article
The Relevance of Follicle Number and Androgens in Metabolic Alterations in Polycystic Ovary Syndrome: A Cross-Sectional Study
by Nicoletta Cera, Joana Pinto, Marica Tina Maccarone and Duarte Pignatelli
J. Pers. Med. 2026, 16(10), 512; https://doi.org/10.3390/jpm16100512 - 30 Sep 2026
Viewed by 178
Abstract
Background/Objectives: Polycystic Ovary Syndrome (PCOS) is characterized by reproductive and metabolic disturbances, including insulin resistance and altered ovarian morphology. The clinical manifestations of PCOS include metabolic, reproductive, and psychological issues that negatively affect quality of life, making PCOS a significant public health concern. [...] Read more.
Background/Objectives: Polycystic Ovary Syndrome (PCOS) is characterized by reproductive and metabolic disturbances, including insulin resistance and altered ovarian morphology. The clinical manifestations of PCOS include metabolic, reproductive, and psychological issues that negatively affect quality of life, making PCOS a significant public health concern. The relationship between follicle number and metabolic alterations across PCOS phenotypes still remains unclear. Methods: We conducted a retrospective cross-sectional study of 289 PCOS patients and 50 controls, assessing insulin resistance, lipid profiles, ovarian volume, and follicle count across phenotypes A, B, and C. We compared the three PCOS phenotypes and identified differences in follicle number, ovarian volume, insulin-related biomarkers, androgens, and LH and FSH. Results: Phenotype A exhibited higher insulin resistance and adverse lipid profiles compared to controls. The follicle number significantly discriminated between phenotypes and is associated with insulin-related alterations, one of the most clinically relevant aspects of PCOS. It is also correlated negatively with insulin resistance, most notably in phenotype B. Ovarian volume even differed among phenotypes but showed weaker metabolic associations. There is also a significant relevance of ovarian dysmorphology in PCOS and its association with hyperinsulinemia and insulin resistance. Conclusions: There is a complex interplay among the ovarian morphology, androgen and metabolic patterns in the different PCOS phenotypes. Follicle number is a relevant marker linked to insulin resistance in PCOS, particularly in phenotype B, supporting its role in clinical phenotyping and potential for guiding personalized management strategies. Full article
(This article belongs to the Section Disease Biomarkers)
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31 pages, 5727 KB  
Article
Effects of Ficus carica L. Leaf Extract on Ipsilateral and Contralateral Testes After Testicular Torsion/Detorsion Injury: Evaluation of Oxidative Stress, Inflammation, and Apoptosis
by Zeynep Yığman, Saadet Özen Akarca Dizakar, Metin Yığman, Mürşide Ayşe Demirel, İpek Süntar, Ali Doğan Dursun, Ayhan İbrahim Aysal, Ayşe Köylü and Suna Ömeroğlu
Int. J. Mol. Sci. 2026, 27(19), 8678; https://doi.org/10.3390/ijms27198678 - 28 Sep 2026
Viewed by 231
Abstract
The current study aimed to investigate the dose-dependent effects of Ficus carica leaf extract on oxidative, inflammatory, and apoptotic processes contributing to ischemia–reperfusion injury in bilateral testes following testicular torsion–detorsion. Forty-eight male Wistar Albino rats were assigned into six groups (n= [...] Read more.
The current study aimed to investigate the dose-dependent effects of Ficus carica leaf extract on oxidative, inflammatory, and apoptotic processes contributing to ischemia–reperfusion injury in bilateral testes following testicular torsion–detorsion. Forty-eight male Wistar Albino rats were assigned into six groups (n= 8): Intact, Sham, Torsion/Detorsion (T/D), T/D + 125, T/D + 250, and T/D + 500. Sixty minutes of left testicular torsion was followed by 56-day reperfusion in all T/D, T/D + 125, T/D + 250, and T/D + 500 groups, and rats in these groups were daily administered with vehicle, 125 mg/kg, 250 mg/kg, and 500 mg/kg F. carica leaf extract, respectively. Sperm, serum, and bilateral testes tissue samples were examined. Sperm count of the contralateral epididymis and serum follicle-stimulating hormone (FSH) level in the T/D + 250 group were higher than in the T/D and T/D + 125 groups. FSH level in the T/D + 500 group was higher compared to the T/D, T/D + 125, and T/D + 250 groups. Total Oxidant Status (TOS) level in the ipsilateral testis of the T/D + 500 group was lower than that of the T/D, T/D + 125, and T/D + 250 groups. The Oxidative Stress Index (OSI) value in the ipsilateral testis was lower in the T/D + 500 group compared to the T/D, T/D + 125, and T/D + 250 groups. Total Antioxidant Status (TAS) level in the contralateral testis of the T/D + 125, T/D + 250, and T/D + 500 groups was elevated compared to the T/D group. TOS level of the contralateral testis in the T/D + 500 group was lower than that in the T/D and T/D + 125 groups. OSI value of the contralateral testis was lower in the T/D + 125, T/D + 250, and T/D + 500 groups than that in the T/D group. TNF-α and IL-10 immunostaining intensities were improved in bilateral testes of the treatment groups compared to the T/D group. Johnsen’s score of the ipsilateral testis in the T/D + 250 and T/D + 500 groups was greater compared to the T/D group. BAX and CASP3 immunostaining intensities were lower in the bilateral testes of the treatment groups than in the T/D group. BCL-2 immunostaining intensity in bilateral testes of the T/D + 250 and T/D + 500 groups was higher than in the T/D group. By exerting antioxidative, anti-inflammatory, and antiapoptotic effects, F. carica leaf extract emerges as a promising therapeutic candidate in testicular ischemia–reperfusion injury. Further studies may help clarify the optimal dosage, potential adverse effects, and fertility outcomes. Full article
(This article belongs to the Special Issue Molecular Research on Ischemia-Reperfusion Injury)
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15 pages, 1117 KB  
Article
Reduced Granulosa Cell AKT2 mRNA Expression in Women with Unexplained Infertility: A Prospective Case–Control Study of ICSI Cycles
by Özgür Uzun, Belgin Devranoğlu, Enis Özkaya, Huri Demirci, Gülden Tunalı, Zehra Sezer, Fatma Beyza Sağ and Emine Elif Güzel Meydanlı
Biomedicines 2026, 14(9), 2108; https://doi.org/10.3390/biomedicines14092108 - 18 Sep 2026
Viewed by 200
Abstract
Background/Objectives: Unexplained infertility (UI) is defined by the absence of detectable abnormality on standard evaluation, which raises the possibility that the causative defect lies at the level of intracellular signaling rather than at the level of gamete number or hormone concentration. The [...] Read more.
Background/Objectives: Unexplained infertility (UI) is defined by the absence of detectable abnormality on standard evaluation, which raises the possibility that the causative defect lies at the level of intracellular signaling rather than at the level of gamete number or hormone concentration. The PI3K/Akt pathway governs primordial follicle activation, granulosa cell survival, and the acquisition of oocyte competence, but AKT2 transcript abundance in the somatic follicular compartment has not been characterized clinically in UI. We compared cumulus/granulosa cell AKT2 transcript levels and follicular fluid Akt and phospho-Akt (Ser473) protein levels between women with UI and women undergoing intracytoplasmic sperm injection (ICSI) for isolated male factor infertility.  Methods: This was a prospective case–control study of 128 women (64 UI, 64 male factor) aged 23–35 years, all stimulated with a GnRH antagonist protocol and recruited December 2020–May 2021. AKT2 expression in cumulus/granulosa cells recovered at denudation was quantified using RT-qPCR (ΔΔCt, GAPDH reference). Total Akt and phospho-Akt (Ser473) were measured in follicular fluid using ELISA and normalized to the number of oocytes retrieved. Oocyte maturation, fertilization, day 3 embryo quality, and day 5 blastocyst quality were assessed using Alpha/ESHRE Istanbul consensus criteria. Correlation analyses were exploratory and reported with Benjamini–Hochberg false discovery rate (FDR) adjustment. Results: Baseline characteristics, including age, body mass index, antral follicle count, AMH, FSH, LH, oocytes retrieved, and duration of infertility, were comparable between groups. Granulosa cell AKT2 ΔCt was higher in the UI group (3.46 ± 1.47 versus 2.68 ± 1.18; p = 0.001), corresponding to a 1.72-fold lower AKT2 transcript level (ΔΔCt 0.78; Cohen’s d = 0.59); the difference persisted after adjustment for age, body mass index, AMH, basal estradiol levels, and previous IVF attempts (adjusted ΔCt difference 0.74, 95% CI 0.25–1.24; p = 0.004). Follicular fluid total Akt (11.55 ± 4.08 versus 11.75 ± 3.60 relative units; p = 0.78) and phospho-Akt (21.05 ± 7.14 versus 19.81 ± 7.24; p = 0.34) did not differ, nor did values normalized per oocyte. Oocyte maturation rate (0.72 ± 0.25 versus 0.76 ± 0.18), fertilization rate (44.6 ± 29.5% versus 42.2 ± 25.6%), day 3 good-quality embryo rate (25.0 ± 25.8% versus 26.6 ± 23.8%), and good-quality blastocyst rate (30.2 ± 25.8% versus 20.5 ± 18.5%) were all comparable. Of 24 exploratory correlations, only two survived FDR adjustment. Both correlations were in the male factor comparison group and both involved the small blastocyst subgroup: total Akt per oocyte (ρ = 0.738) and phospho-Akt per oocyte (ρ = 0.728) versus good-quality blastocyst rate (n = 17; FDR p = 0.011). AKT2 ΔCt did not correlate with any embryological endpoint in either group. Conclusions: Cumulus and granulosa cell AKT2 mRNA was reduced approximately 1.7-fold in women with unexplained infertility, despite indistinguishable ovarian reserve, ovarian response, and embryological performance and despite unchanged follicular fluid Akt protein. Because the comparison group consisted of women from couples undergoing ICSI for male factor infertility rather than women of proven fertility, the difference cannot be attributed specifically to unexplained infertility, and the findings describe transcript abundance rather than pathway activity. Confirmation against a fertile comparison group, with protein-level assessment in the same cells and clinical pregnancy endpoints, is required. Full article
(This article belongs to the Special Issue Female Fertility: Insights from Molecular Perspective)
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23 pages, 647 KB  
Article
Abdominal Obesity, Testosterone Deficiency and Sedentary Lifestyle in Young Men from the General Population: The Relationship with Semen Quality, Hormonal and Metabolic Status
by Ludmila Osadchuk and Alexander Osadchuk
Biomedicines 2026, 14(9), 2097; https://doi.org/10.3390/biomedicines14092097 - 17 Sep 2026
Viewed by 307
Abstract
Background: The demographic crisis observed in industrialized countries has been accompanied by a decline in the reproductive potential of human populations. One of the causes for the global deterioration in men’s reproductive health is adiposity and sedentary lifestyle, leading to reduced fertility and [...] Read more.
Background: The demographic crisis observed in industrialized countries has been accompanied by a decline in the reproductive potential of human populations. One of the causes for the global deterioration in men’s reproductive health is adiposity and sedentary lifestyle, leading to reduced fertility and a decrease in androgen status. The aim of the study was to assess the association between abdominal obesity and semen parameters, including sperm DNA fragmentation, as well as key indicators of hormonal and metabolic status in young men from the general population. Methods: Our cross-sectional study was conducted among Russian and Belarusian men living in six cities. The examination of men (n = 1283, median age 23 years) included questionnaires, anthropometry, and the collection of peripheral blood and semen samples. Semen analysis was conducted according to WHO guidelines. Sperm DNA fragmentation index (DFI) was evaluated using the SCSA method. The serum and seminal zinc concentration was determined using spectrophotometry and direct calorimetry. Hormonal and metabolic levels were measured using commercial kits. Waist circumference (WC) was used as a surrogate marker of abdominal adiposity. Participants were allocated to three phenotypes: non-obese (control, WC < 94 cm), excess abdominal fat (94 ≤ WC < 102 cm) and abdominal obesity (WC ≥ 102 cm). Results: In our study population, 85.8% of participants were young (under 30 years of age), 8.6% had excess abdominal fat, 5.7% had abdominal obesity (AO), and 65.2% had normozoospermia. Men with AO were characterized by a decrease in semen volume, total sperm count, sperm concentration and progressive motility compared to the non-obese control. DFI was significantly higher in obese compared to non-obese men. Obese participants had significantly lower testosterone and inhibin B levels, but higher FSH and leptin levels compared to non-obese men. Men with AO had elevated serum zinc levels but reduced seminal zinc content. Abdominal obesity was also associated with significant metabolic changes, in particular, with increased levels of triglycerides, total cholesterol, low-density lipoproteins, fasting glucose and uric acid. AO-related testosterone deficiency (serum testosterone level ≤ 12.1 nmol/L) was detected in 38.7% of obese men and was accompanied by elevated DFI, levels of FSH, and zinc, as well as unfavorable changes in metabolic indicators. Physically active AO men (who engaged in recreational sports or physical labor) demonstrated reduced anthropometric indicators of AO and leptin levels, increased LH and testosterone levels, and improved carbohydrate and lipid metabolism compared to sedentary AO men. Conclusions: AO is accompanied by a decrease in the activity of Leydig and Sertoli cells, as well as an imbalance of the hypothalamic–pituitary–testicular axis and metabolic status. AO, associated with testosterone deficiency or a sedentary lifestyle, is a potential risk factor for the weakening of male reproductive health. However, physically active stout men showed more favorable anthropometric, hormonal, and metabolic indicators compared with sedentary stout men. In the long term, obese men who ignore a correction of sedentary lifestyle are not protected from a decline in reproductive health. Full article
(This article belongs to the Special Issue Molecular Research in Obesity, 2nd Edition)
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15 pages, 1207 KB  
Article
Body Mass Index-Related Alterations in Gonadotropin Secretion Among Women with Polycystic Ovary Syndrome Compared with Healthy Controls
by Saad Al-Fawaeir
Diseases 2026, 14(9), 341; https://doi.org/10.3390/diseases14090341 - 16 Sep 2026
Viewed by 280
Abstract
Aim: To investigate the association between body mass index (BMI) and gonadotropin secretion, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH/FSH ratio, among women with polycystic ovary syndrome (PCOS), and to compare these parameters with healthy women. Patients and Methods: [...] Read more.
Aim: To investigate the association between body mass index (BMI) and gonadotropin secretion, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH/FSH ratio, among women with polycystic ovary syndrome (PCOS), and to compare these parameters with healthy women. Patients and Methods: This comparative cross-sectional analytical study included 400 women aged 18–35 years recruited from outpatient gynecology and endocrinology clinics at private-sector medical centers in Irbid, Jordan, between June 2025 and April 2026. The study included 200 women diagnosed with PCOS according to the Rotterdam criteria and 200 age-comparable healthy controls. The PCOS group was stratified into four BMI categories (<25, 25–<28, 28–<31, and ≥31 kg/m2), with 50 women in each category. Clinical and anthropometric characteristics were assessed, and serum LH and FSH concentrations were measured. The LH/FSH ratio was calculated for each participant. Differences between groups were evaluated using appropriate statistical tests, while one-way analysis of variance was used to compare PCOS subgroups according to BMI. Pearson’s correlation analysis was used to assess associations between BMI and gonadotropin parameters. Results: The mean age was comparable between women with PCOS and healthy controls (26.31 ± 5.36 vs. 26.47 ± 5.16 years; p = 0.23). Women with PCOS had significantly higher BMI than controls (27.85 ± 3.47 vs. 22.81 ± 2.29 kg/m2; p < 0.001). Among women with PCOS, menstrual irregularity, hirsutism, acne, infertility, and polycystic ovarian morphology were observed in 87.5%, 79.5%, 78.5%, 70.0%, and 100%, respectively. Serum LH was significantly higher in women with PCOS than in controls (8.44 ± 2.61 vs. 6.53 ± 1.16 IU/L; p < 0.001), whereas FSH was significantly lower (4.64 ± 0.98 vs. 7.96 ± 1.18 IU/L; p < 0.001), resulting in a higher LH/FSH ratio (1.84 ± 0.50 vs. 0.83 ± 0.20; p < 0.001). Within the PCOS group, LH progressively decreased across increasing BMI categories, from 11.58 ± 1.26 IU/L in women with BMI < 25 kg/m2 to 5.40 ± 1.29 IU/L in those with BMI ≥ 31 kg/m2 (p < 0.001). Similarly, the LH/FSH ratio decreased from 2.46 ± 0.18 to 1.28 ± 0.23 across these BMI categories (p < 0.001), whereas FSH did not differ significantly (p = 0.07). BMI showed strong inverse correlations with LH (r = −0.870, p < 0.001) and the LH/FSH ratio (r = −0.869, p < 0.001), but not with FSH (r = −0.126, p = 0.075). Conclusions: Women with PCOS demonstrated a distinct gonadotropin profile characterized by higher LH and LH/FSH ratio and lower FSH compared with healthy controls. Among women with PCOS, increasing BMI was strongly associated with lower LH concentrations and LH/FSH ratios. These findings highlight the importance of considering BMI when interpreting gonadotropin profiles in PCOS, although prospective studies are required to determine whether changes in body weight directly influence gonadotropin secretion and reproductive outcomes. Full article
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18 pages, 506 KB  
Article
The Impact of Chemotherapy on Gonadal Function in Female Patients with Hodgkin and Non-Hodgkin Lymphoma: A Comprehensive Analysis of Hormonal Kinetics and Implications for Fertility and Contraceptive Planning
by Angeliki N. Georgopoulou, Theodoros P. Vassilakopoulos, Andreas Giannakou, Neoklis A. Georgopoulos, Sophia Kalantaridou, Konstantinos Keramaris, Eleni Lalou, Eleni Loukari, Konstantinos Konstantopoulos, Marina P. Siakantaris, Anastasia Kopsaftopoulou, Chrysovalanto Chatzidimitriou, Maria Arapaki, Marina Belia, Iliana Konstantinou, Ioannis Asimakopoulos, Irene Mammali and Maria K. Angelopoulou
Cancers 2026, 18(17), 2855; https://doi.org/10.3390/cancers18172855 - 3 Sep 2026
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Abstract
Background/Objectives: Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL) affect young women, with cure rates exceeding 80%. Treatment-related gonadal insufficiency is recognized for its impact on fertility, yet fertility preservation remains underutilized, and prospective data are limited. The aim of this [...] Read more.
Background/Objectives: Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL) affect young women, with cure rates exceeding 80%. Treatment-related gonadal insufficiency is recognized for its impact on fertility, yet fertility preservation remains underutilized, and prospective data are limited. The aim of this study is to prospectively evaluate gonadal function in women ≤40 years old with lymphoma undergoing chemotherapy. Methods: Ovarian reserve and endocrine ovarian function were evaluated by sequential measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, and estradiol at diagnosis, during, and after chemotherapy. Results: 81 female patients ≤40 years old were enrolled, including 53 with HL and 28 with NHL (16 with PMBCL). HL patients had significantly lower AMH values for their respective age group compared to all other diagnoses (p = 0.05), which was more striking for patients ≤30 years old (p = 0.039), indicating pre-existing reduced ovarian reserve in HL. In HL, both FSH and AMH levels indicate gonadal dysfunction for at least six months post-chemotherapy, with AMH serving as a more sensitive biomarker than FSH. For PMBCL patients treated with R-DA-EPOCH, AMH suppression was noticed, with no evidence of recovery up to 18 months post-treatment. At all time points, the PMBCL patients had significantly lower AMH values compared to the HL patients (AMH6: p = 0.03, AMH12 and AMH18: p = 0.05). AMH emerged as the most sensitive marker of ovarian damage, with pretreatment levels <7 pmol/L predicting impaired ovarian reserve in HL patients. Conclusions: For HL, the pretreatment cut-off of 7 pmol/L could discriminate patients with ovarian insufficiency post-treatment, whereas no statistically significant predictive association was identified in PMBCL. These findings require validation in larger cohorts. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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12 pages, 1388 KB  
Communication
Circulating GnRH, FSH, and LH Levels in Keratoconus and Down Syndrome: A Cross-Sectional Comparison
by Pawan Shrestha, Paulina Escandon, Jesper Hjortdal, Lito Ramirez, Rajesh Nandy, Melissa Petersen and Dimitrios Karamichos
Appl. Sci. 2026, 16(17), 8745; https://doi.org/10.3390/app16178745 - 3 Sep 2026
Viewed by 270
Abstract
Down syndrome (DS) is a common genetic disorder that has been strongly associated with keratoconus (KC). However, the underlying mechanism linking these conditions remains unexplored. KC is a corneal disorder characterized by corneal steepening, thinning, and scarring. The primary objective of this study [...] Read more.
Down syndrome (DS) is a common genetic disorder that has been strongly associated with keratoconus (KC). However, the underlying mechanism linking these conditions remains unexplored. KC is a corneal disorder characterized by corneal steepening, thinning, and scarring. The primary objective of this study was to determine the role of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the context of DS and KC. A total of 58 healthy (29 male, 29 female), 227 KC (167 male, 60 female), and 80 DS participants (44 male, 36 female) were recruited. Hormone levels from plasma were analyzed using enzyme-linked immunosorbent assays, and differences between disease status, sex, and age were examined. GnRH was reduced in KC compared to healthy and DS participants, particularly in males. In contrast, FSH was elevated across both sexes in DS participants compared to healthy and KC participants. LH was also significantly elevated in DS, particularly among females and among participants from 30–45 age group, mirroring the pattern seen for FSH. These cross-sectional findings reveal distinct hormonal patterns across KC and DS cohorts while providing novel descriptive data on hypothalamic–pituitary–gonadal axis hormones. Further studies are warranted to determine the relationship between gonadotropins and the phenotypic manifestations in these populations. Full article
(This article belongs to the Special Issue Trends and Prospects in Retinal and Corneal Diseases)
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16 pages, 24169 KB  
Article
Combined Metabolomic and Transcriptomic Analysis Identifies Metabolic Signatures and Networks Associated with Semen Quality in Geese
by Lei Zhang, Guobo Sun, Rui Zhu, Gansheng Zhang, Qingyi Zhou, Yue Wang and Xiujun Duan
Animals 2026, 16(17), 2763; https://doi.org/10.3390/ani16172763 - 2 Sep 2026
Viewed by 354
Abstract
Semen quality is a critical determinant of male fertility in poultry, yet the testicular metabolic and molecular mechanisms underlying seminal traits in geese remain poorly understood. This study aimed to characterize the testicular metabolomic and transcriptomic profiles of Zhedong white geese with divergent [...] Read more.
Semen quality is a critical determinant of male fertility in poultry, yet the testicular metabolic and molecular mechanisms underlying seminal traits in geese remain poorly understood. This study aimed to characterize the testicular metabolomic and transcriptomic profiles of Zhedong white geese with divergent semen quality, and to identify key regulatory pathways and candidate genes influencing semen quality. Untargeted metabolomics and RNA sequencing were performed on testicular tissues from geese with high (H) and low (L) semen quality. Serum hormone measurements revealed significantly increased testosterone (T) and decreased follicle-stimulating hormone (FSH) levels in the H group compared with the L group (p < 0.05). Metabolomic analysis identified 207 differential metabolites (DEMs), which were significantly enriched in glycosylphosphatidylinositol (GPI)-anchor biosynthesis, the citrate (TCA) cycle, and alanine, aspartate, and glutamate metabolism. Integrated transcriptomic and metabolomic analyses, combined with KEGG Markup Language (KGML) network analysis, revealed a candidate regulatory network involving potential metabolites (arachidonic acid, pyruvic acid, fumaric acid, malic acid and beta-alanine), signaling pathways (the citrate (TCA) cycle, arginine biosynthesis, ABC transporters, glycine/serine/threonine metabolism, and efferocytosis), and candidate genes (PLCB1, PLCB2, NT5C1A, TAT, LOC106042968 and ABCG8). Notably, PLCB1, which was significantly up-regulated in the H group, emerged as a candidate gene of particular interest that may be implicated in the regulation of metabolic pathways underlying semen quality in ganders. These findings provide novel insights into the testicular metabolic and transcriptomic determinants of semen quality in geese, and implicate PLCB1 and associated pathways as potential targets for improving male fertility in poultry. Full article
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