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Search Results (1,857)

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19 pages, 4551 KB  
Review
Fatty Acid Amide Hydrolase Signaling and Ovarian Disorders: From Molecular Mechanism to Clinical Significance
by Qinghe Lin, Zhenghong Zhang, Defan Wang, Fan Wang and Zhengchao Wang
Molecules 2026, 31(3), 556; https://doi.org/10.3390/molecules31030556 - 5 Feb 2026
Abstract
Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology [...] Read more.
Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology is receiving increasing attention. Accumulating evidence indicates that FAAH participates in several important ovarian processes, including follicular development, steroid hormone synthesis, ovulation, and luteal function. In this review, we outline the biochemical properties of FAAH and its spatial distribution in ovarian tissues, with a particular focus on how FAAH-mediated AEA metabolism contributes to intraovarian signaling. Furthermore, we highlight the potential implications of altered FAAH activity in ovarian disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and infertility. By integrating molecular observations with clinical findings, this work provides updated perspectives on FAAH as both a physiological regulator and a potential therapeutic target in reproductive medicine. Full article
(This article belongs to the Special Issue Signaling Pathways as Targets in Disease Therapy)
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19 pages, 7165 KB  
Article
A Pseudotumorous Syndrome Associated with an As-Yet-Unidentified Eukaryotic Parasite Causing Functional Gonadal Arrest in Largefin Longbarbel Catfish (Hemibagrus macropterus)
by Yang Feng, Senyue Liu, Hongyu Ke, Huadong Li, Han Zhao, Xinyan Dang, Chengyan Mou, Jian Zhou, Zhipeng Huang, Yongqiang Deng and Qiang Li
Microorganisms 2026, 14(2), 362; https://doi.org/10.3390/microorganisms14020362 - 3 Feb 2026
Abstract
This study presents the first documented case of a disease syndrome in cultured largefin longbarbel catfish (Hemibagrus macropterus). The condition is characterized by massive abdominal pseudotumor formation, severe cachexia, and functional gonadal arrest. Comprehensive pathological investigation revealed that the pseudotumor was [...] Read more.
This study presents the first documented case of a disease syndrome in cultured largefin longbarbel catfish (Hemibagrus macropterus). The condition is characterized by massive abdominal pseudotumor formation, severe cachexia, and functional gonadal arrest. Comprehensive pathological investigation revealed that the pseudotumor was encapsulated by fibroblasts and primarily composed of host-derived, poorly differentiated hyperplastic cells, interspersed with invasive, basophilic Type III cells. These cells and associated inflammatory–fibrotic lesions were also disseminated in the gill, kidney and spleen. Systematic diagnostic approaches, including microbiology and transmission electron microscopy, found no evidence of conventional bacterial or viral pathogens. Metagenomic analysis further supported these findings and suggested a link to infection by an as-yet-unidentified eukaryotic parasite, with Microsporidia or Ichthyosporea being the primary candidates. Functional (KEGG) profiling of the pseudotumor tissue further revealed a molecular signature consistent with active cellular proliferation and metabolism. We propose that the pseudotumor acts as a metabolically active “nutrient sink,” driving the systemic catabolism that underlies the severe cachexia and reproductive arrest. This work provides the first case of a eukaryotic parasite-induced pseudotumorous syndrome in fish, which represents an emerging threat to conservation aquaculture and offering novel insights into parasite-mediated host metabolic hijacking and tumor-mimicry. Full article
(This article belongs to the Section Microbiomes)
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18 pages, 13877 KB  
Article
Oligosaccharides Reduce the Survival of Apis cerana and Disrupt the Gut Symbiont Gilliamella
by Yulong Guo, Haoyuan Zhang, Wenzheng Zhao, Yakai Tian, Dan Yue, Xueyang Gong and Kun Dong
Insects 2026, 17(2), 169; https://doi.org/10.3390/insects17020169 - 3 Feb 2026
Viewed by 36
Abstract
Honeybees are vital pollinators that contribute substantially to global ecosystem stability and agricultural productivity. Camellia reticulata, a cross-pollinated crop species, depends on honeybees for successful reproduction. Apis cerana shows reluctance to pollinate C. reticulata, yet the molecular mechanisms underlying this phenomenon [...] Read more.
Honeybees are vital pollinators that contribute substantially to global ecosystem stability and agricultural productivity. Camellia reticulata, a cross-pollinated crop species, depends on honeybees for successful reproduction. Apis cerana shows reluctance to pollinate C. reticulata, yet the molecular mechanisms underlying this phenomenon remain unexplored. In this study, we performed controlled feeding experiments in which adult worker A. cerana were supplied with stachyose, raffinose, and their combination. We assessed physiological traits including survival rate, sucrose solution consumption, and body weight gain, alongside histological changes in intestinal cell structures. We conducted RNA-seq of gut tissues as well as 16S rRNA sequencing and metabolomic profiling. Our findings revealed that the mixed oligosaccharide treatment significantly reduced the survival rate of workers, and three oligosaccharide treatments significantly reduced sucrose consumption in A. cerana. Both mixed and single-oligosaccharide treatments caused pronounced intestinal cell damage and disrupted the gut microbial community structure. Among the gut microbes, Gilliamella exhibited the most substantial decline in the stachyose group. Metabolomic analysis further demonstrated that oligosaccharide feeding significantly altered amino acid and galactose metabolism pathways, which may play critical roles in oligosaccharide utilization and directly influence honeybee survival. In summary, this study provides new insights into the molecular mechanisms underlying A. cerana mortality associated with C. reticulata pollination. These findings not only enhance our understanding of host-diet-microbiota interactions in honey bees but also offer a theoretical basis for the integrated management of A. cerana for C. reticulata pollination and the development of oligosaccharide-adapted bee diets. Full article
(This article belongs to the Section Social Insects and Apiculture)
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21 pages, 3861 KB  
Article
Achieving Lasting Umbilical Cord Decontamination and Sustainable Stem Cell Sourcing by Combining Plasma-Functionalized Liquid and Ultrasound
by Yuanyuan Pan, Alexander Pogoda, Monika Röntgen, Juergen F. Kolb and Sybille Hasse
Foods 2026, 15(3), 532; https://doi.org/10.3390/foods15030532 - 3 Feb 2026
Viewed by 45
Abstract
The growing demand for alternative meat products is accelerating research into reproductive cell sources for cell-based meat processes, also called cultured meat. Porcine umbilical cord tissue is recognized as an advantageous source of mesenchymal stem cells (MSCs). However, effective decontamination must be achieved [...] Read more.
The growing demand for alternative meat products is accelerating research into reproductive cell sources for cell-based meat processes, also called cultured meat. Porcine umbilical cord tissue is recognized as an advantageous source of mesenchymal stem cells (MSCs). However, effective decontamination must be achieved without compromising tissue integrity and cell recovery. In this study, we evaluated the decontamination of porcine umbilical cords using plasma-functionalized liquid (PFL) generated by a microwave-driven plasma source. It was applied alone and in combination with ultrasound, with the combined approach demonstrating superior performance. Specifically, the ultrasound–PFL combination treatment reduced the initial microbial load of individual tissue samples, ranging from 4.08 to 7.41 log10 CFU/g, approaching the limit of detection of the applied microbiological assays. Statistical analysis indicated a significant contribution of both PFL and ultrasound to microbial reduction, while mesenchymal stem cell yields (5.4 × 105 cells/g tissue) and cell viability (84%) remained comparable to antibiotic-rinsed controls. Recovered cells retained functional capacity, as demonstrated by successful 3D spheroid formation. These results highlight ultrasound-assisted PFL rinsing as an efficient, long-lasting, and antibiotic-free decontamination strategy without compromising tissue compatibility. This study thereby extends the application of plasma-functionalized liquids and demonstrates the feasibility of sustainable stem cell sourcing. It offers opportunities in cultured meat bioprocessing. Full article
(This article belongs to the Special Issue Non-Thermal Processing Technologies for Sustainable Food Processing)
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15 pages, 1279 KB  
Article
Reproductive Biology and Biochemical Composition of the Reared European Clam Ruditapes decussatus (Mollusca: Bivalvia) in Oualidia Lagoon, Morocco
by Mouhcine Medlouh, Ibtissam Doukilo, Ahmed Errhif, Mohamed Id Halla and Oum Keltoum Belhsen
Oceans 2026, 7(1), 13; https://doi.org/10.3390/oceans7010013 - 2 Feb 2026
Viewed by 54
Abstract
The reproductive cycle of the European clam Ruditapes decussatus reared in suspended double-net trays in the Oualidia Lagoon was investigated from October 2017 to February 2019. This study aimed to characterize gonadal development through histological analysis, gonadal index assessment, and the biochemical composition [...] Read more.
The reproductive cycle of the European clam Ruditapes decussatus reared in suspended double-net trays in the Oualidia Lagoon was investigated from October 2017 to February 2019. This study aimed to characterize gonadal development through histological analysis, gonadal index assessment, and the biochemical composition of key macromolecules (proteins, lipids, and carbohydrates) over an annual cycle. The results revealed that R. decussatus undergoes a prolonged spawning period from April to December, with a peak in October when 100% of the population reached the maturation stage (stage IIIA). A sexual rest phase was observed between November 2017 and December 2017. An overall sex ratio of 1:0.8 was observed, indicating a slight female bias, with no significant deviations. Statistical analyses highlighted a correlation between the gonadal index and seawater temperature, suggesting that temperature plays a crucial role in regulating reproductive activity. Biochemical analyses showed that proteins were the predominant macromolecule in clam tissues, followed by lipids and carbohydrates. Seasonal variations in biochemical composition were observed; however, no direct correlation was found between biochemical compound levels and the gonadal index (p > 0.05). These findings provide valuable insights into the reproductive biology of R. decussatus under suspended aquaculture conditions, contributing to improved management and optimization of farming practices. Full article
22 pages, 1834 KB  
Review
Therapeutic Effects of Vitamins in Endometriosis Patients: A Systematic Review of Randomized Controlled Trials
by Sophia Tsokkou, Alkis Matsas, Ioannis Konstantinidis, Evaggelia Karopoulou, Theodora Papamitsou and Eleni Stamoula
Int. J. Mol. Sci. 2026, 27(3), 1476; https://doi.org/10.3390/ijms27031476 - 2 Feb 2026
Viewed by 142
Abstract
Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, which frequently results in dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. While hormonal medications [...] Read more.
Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, which frequently results in dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. While hormonal medications and surgical procedures are common treatments, they are often constrained by adverse effects and high recurrence rates. The aim was to systematically identify, critically appraise, and synthesize randomized controlled trials evaluating vitamin D, C, and E supplementation in women with endometriosis, focusing on their effects on pelvic pain, dysmenorrhea, dyspareunia, quality of life, oxidative and inflammatory biomarkers, and fertility-related outcomes, and to highlight methodological gaps that can inform future research and integrated therapeutic strategies. Following PRISMA guidelines, seven eligible RCTs were identified from databases including PubMed, Scopus, and ScienceDirect. The quality of these studies was assessed using the Jadad Scoring System and Cochrane RoB 2 tool. High-dose supplementation of vitamin D (50,000 IU) was found to significantly reduce pelvic pain and improve biochemical markers such as hs-CRP and total antioxidant capacity (TAC). Vitamin D appears to modulate endometrial pathways by reducing active β-catenin protein activity, which may disrupt signaling associated with lesion invasion and survival. Additionally, combined Vitamin C and E therapy (typically 1000 mg/day of Vitamin C and 800 IU/day of Vitamin E) acts synergistically to scavenge free radicals. This intervention significantly decreased oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS). Patients reported significant improvements in symptoms, including a 43% reduction in daily pelvic pain and a 37% reduction in dysmenorrhea. Despite physiological improvements, there was no statistically significant increase in pregnancy rates observed across the trials. Vitamin supplementation with D, C, and E represents a safe, low-cost adjunct therapy that can effectively mitigate endometriosis-related oxidative stress and pelvic pain. While these vitamins show promise for symptom relief, further research with larger sample sizes is required to determine their long-term impact on fertility outcomes and lesion regression. Full article
(This article belongs to the Special Issue Macro- and Micronutrients in Health and Diseases)
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20 pages, 3317 KB  
Article
Study on the Effect of N-Carbamylglutamate (NCG) on Reproductive Performance and Regulation Mechanism of Primary Lake Sheep
by Tianli Gao, Chunyang Li, Juanshan Zheng, Yingpai Zhaxi, Yuan Cai, Rongxin Zang, Huixia Liu, Yanmei Yang, Sai Li, Xiaodi Shi and Chen Huang
Animals 2026, 16(3), 464; https://doi.org/10.3390/ani16030464 - 2 Feb 2026
Viewed by 98
Abstract
The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually [...] Read more.
The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level. Full article
(This article belongs to the Section Animal Reproduction)
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21 pages, 506 KB  
Review
Women with Endometriosis: A Narrative Review of Adiposity and Metabolic Function from a Biopsychosocial and Intersectional Perspective
by Carmen M. Galvez-Sánchez, Julio A. Camacho-Ruiz, Ana M. Contreras-Merino and Rosa M. Limiñana-Gras
Women 2026, 6(1), 12; https://doi.org/10.3390/women6010012 - 2 Feb 2026
Viewed by 72
Abstract
Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. [...] Read more.
Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. This narrative review synthesized current evidence on the relationship between adiposity, metabolic and inflammatory markers, and endometriosis from a biopsychosocial and intersectional perspective. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for peer-reviewed studies published in English over the past decade.: Results pointed out that endometriosis significantly affects inflammatory activity within adipose tissue, especially in visceral adipose tissue. Studies also reported reduced adipocyte size and altered adipose tissue function. The endometriosis cytokine profile exhibited a pattern of systemic and tissue-specific inflammatory activation (i.e., elevated levels of interleukin-6 and monocyte chemoattractant protein-1). Sociodemographic factors (i.e., age, race/ethnicity, socioeconomic status, and educational level) also play a significant role in differences in symptomatology, disease course, and healthcare access. To sum up, endometriosis need to be considered as a multisystem condition related to metabolic, inflammatory, and psychosocial factors. It is necessary to adopt a biopsychosocial and intersectional perspective to improve diagnosis and support more equitable and personalized therapeutic approaches. Full article
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17 pages, 2700 KB  
Review
Reproductive Toxicity of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer: A Case Report with a Literature Review
by Cristina Tanase-Damian, Nicoleta Zenovia Antone, Diana Loreta Paun, Ioan Tanase and Patriciu Andrei Achimaș-Cadariu
Diseases 2026, 14(2), 51; https://doi.org/10.3390/diseases14020051 - 30 Jan 2026
Viewed by 83
Abstract
Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the [...] Read more.
Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic–pituitary–gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity. Full article
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23 pages, 2541 KB  
Review
Artificial Intelligence in Endometriosis Imaging: A Scoping Review
by Rawan AlSaad, Thomas Farrell, Ali Elhenidy, Shima Albasha and Rajat Thomas
AI 2026, 7(2), 43; https://doi.org/10.3390/ai7020043 - 29 Jan 2026
Viewed by 221
Abstract
Endometriosis is a chronic gynecological condition characterized by endometrium-like tissue outside the uterus. In clinical practice, diagnosis and anatomical mapping rely heavily on imaging, yet performance remains operator- and modality-dependent. Artificial intelligence (AI) has been increasingly applied to endometriosis imaging. We conducted a [...] Read more.
Endometriosis is a chronic gynecological condition characterized by endometrium-like tissue outside the uterus. In clinical practice, diagnosis and anatomical mapping rely heavily on imaging, yet performance remains operator- and modality-dependent. Artificial intelligence (AI) has been increasingly applied to endometriosis imaging. We conducted a PRISMA-ScR-guided scoping review of primary machine learning and deep learning studies using endometriosis-related imaging. Five databases (MEDLINE, Embase, Scopus, IEEE Xplore, and Google Scholar) were searched from 2015 to 2025. Of 413 records, 32 studies met inclusion and most were single-center, retrospective investigations in reproductive-age cohorts. Ultrasound predominated (50%), followed by laparoscopic imaging (25%) and MRI (22%); ovarian endometrioma and deep infiltrating endometriosis were the most commonly modeled phenotypes. Classification was the dominant AI task (78%), typically using convolutional neural networks (often ResNet-based), whereas segmentation (31%) and object detection (3%) were less explored. Nearly all studies relied on internal validation (97%), most frequently simple hold-out splits with heterogeneous, accuracy-focused performance reporting. The minimal AI-method quality appraisal identified frequent methodological gaps across key domains, including limited reporting of patient-level separation, leakage safeguards, calibration, and data and code availability. Overall, AI-enabled endometriosis imaging is rapidly evolving but remains early-stage; multi-center and prospective validation, standardized reporting, and clinically actionable detection–segmentation pipelines are needed before routine clinical integration. Full article
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39 pages, 4336 KB  
Systematic Review
Hodgkin Lymphoma—The Effect of Chemotherapy on Gonadal Function and Fertility Is Strongly Related to the Treatment Regimen, Age, and Sex: A Systematic Review and Meta-Analysis
by Mareike Roth-Hochreutener, Maria Karakitsiou, Angela Vidal, Susanna Weidlinger, Janna Pape, Tanya Karrer, Karolin Behringer and Michael von Wolff
Cancers 2026, 18(3), 425; https://doi.org/10.3390/cancers18030425 - 28 Jan 2026
Viewed by 103
Abstract
Background/Objectives: Hodgkin lymphoma (HL) primarily affects individuals of reproductive age, making gonadal dysfunction after chemotherapy a critical survivorship concern. While fertility preservation options including gamete and gonadal tissue cryopreservation are available before treatment, evidence-based counseling requires regimen-specific risk estimates accounting for patient [...] Read more.
Background/Objectives: Hodgkin lymphoma (HL) primarily affects individuals of reproductive age, making gonadal dysfunction after chemotherapy a critical survivorship concern. While fertility preservation options including gamete and gonadal tissue cryopreservation are available before treatment, evidence-based counseling requires regimen-specific risk estimates accounting for patient age and sex. Therefore, a meta-analysis was performed to assess presumed infertility in HL patients, stratified by chemotherapy regimen, age, and sex. Methods: This systematic review and meta-analysis, conducted within the FertiTOX project, included studies published between 2000 and February 2024. Eligible studies reported gonadal function outcomes ≥ 1 year after chemotherapy, excluding patients who received pelvic radiotherapy or stem cell transplantation, or had recurrent disease. Presumed infertility was defined by surrogate markers, including amenorrhea, premature ovarian failure, or abnormal hormonal levels in women, and azoospermia, oligozoospermia, or abnormal hormonal levels in men. Results: Of 2376 screened studies, 50 were included (meta-analysis: 43 studies; 5564 female and 1631 male patients). Overall presumed infertility prevalence was 21% in women (95% CI: 0.14–0.29) and 45% in men (95% CI: 0.29–0.62). The highest prevalence occurred after BEACOPP (women 38%; men 81%), while ABVD was associated with the lowest (6% each in women and men). Childhood/adolescent HL treatment resulted in lower prevalence in women (8%) but remained high in men (67%). Conclusions: Fertility risk depends on regimen, age, and sex, requiring tailored counseling. For female children/adolescents and all patients receiving ABVD, post-treatment fertility evaluation and treatment may suffice. However, pre-treatment fertility preservation is strongly recommended for male adolescents and patients receiving other regimens. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
23 pages, 625 KB  
Review
The Gut–Extracellular Vesicle–Mitochondria Axis in Reproductive Aging: Antioxidant and Anti-Senescence Mechanisms
by Efthalia Moustakli, Christina Messini, Anastasios Potiris, Athanasios Zikopoulos, Ioannis Arkoulis, Alexios Kozonis, Theodoros Karampitsakos, Pavlos Machairoudias, Nikolaos Machairiotis, Panagiotis Antsaklis, Periklis Panagopoulos, Sofoklis Stavros and Ekaterini Domali
Antioxidants 2026, 15(2), 174; https://doi.org/10.3390/antiox15020174 - 28 Jan 2026
Viewed by 240
Abstract
Cellular senescence, mitochondrial dysfunction, and cumulative oxidative stress (OS) are the main causes of the progressive decreases in oocyte and sperm quality that define reproductive age. There is growing evidence that these processes are controlled by systemic variables, such as metabolites produced from [...] Read more.
Cellular senescence, mitochondrial dysfunction, and cumulative oxidative stress (OS) are the main causes of the progressive decreases in oocyte and sperm quality that define reproductive age. There is growing evidence that these processes are controlled by systemic variables, such as metabolites produced from the gut microbiome and extracellular vesicle (EV)-mediated intercellular communication, rather than being exclusively regulated at the tissue level. Antioxidant enzymes, regulatory microRNAs, and bioactive lipids that regulate mitochondrial redox balance, mitophagy, and inflammatory signaling are transported by EVs derived from reproductive organs, stem cells, immune cells, and the gut microbiota. Concurrently, microbiome-derived metabolites such as urolithin A, short-chain fatty acids, and polyphenol derivatives enhance mitochondrial quality control, activate antioxidant pathways, and suppress senescence-associated secretory phenotypes. This narrative review integrates the most recent research on the relationship between redox homeostasis, mitochondrial function, gut microbiota activity, and EV signaling in the context of male and female reproductive aging. We propose an emerging gut–EV–mitochondria axis as a unified framework through which systemic metabolic and antioxidant signals affect gamete competence, reproductive tissue function, and fertility longevity. Finally, we discuss therapeutic implications, including microbiome modulation, EV-based interventions, and senotherapeutic strategies, highlighting key knowledge gaps and future research directions necessary for clinical translation. Full article
(This article belongs to the Special Issue Oxidative Stress and Human Reproduction)
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19 pages, 3013 KB  
Article
Dynamic Transcriptome Profiling Reveals Key Regulatory Networks Underlying Curd Development in Cauliflower (Brassica oleracea L. botrytis)
by Shuting Qiao, Xiaoguang Sheng, Mengfei Song, Huifang Yu, Jiansheng Wang, Yusen Shen, Sifan Du, Jiaojiao Li, Liang Sun and Honghui Gu
Int. J. Mol. Sci. 2026, 27(3), 1308; https://doi.org/10.3390/ijms27031308 - 28 Jan 2026
Viewed by 202
Abstract
Cauliflower (Brassica oleracea var. botrytis) curd formation is a highly complex developmental process governed by tightly coordinated genetic and physiological regulation. Here, we performed transcriptome sequencing of curd and peduncle tissues across multiple developmental stages, generating 171.52 Gb of high-quality data. [...] Read more.
Cauliflower (Brassica oleracea var. botrytis) curd formation is a highly complex developmental process governed by tightly coordinated genetic and physiological regulation. Here, we performed transcriptome sequencing of curd and peduncle tissues across multiple developmental stages, generating 171.52 Gb of high-quality data. Genes associated with photosynthesis and glucosinolate biosynthesis were strongly upregulated in the shoot apical meristem (SAM), highlighting substantial metabolic investment during the pre-initiation phase of curd morphogenesis. Key floral transition regulators, particularly AP2 and MADS-box transcription factors, were activated to drive the vegetative-to-reproductive switch and initiate curd primordia, ultimately giving rise to the arrested inflorescence architecture characteristic of cauliflower. Furthermore, hormone signaling pathways—including auxin (AUX), jasmonic acid (JA), and brassinosteroid (BR)—showed marked activation during SAM proliferation and peduncle elongation, underscoring their crucial roles in structural patterning. Collectively, our findings delineate an integrated regulatory network that links metabolic activity, hormone signaling, and developmental programs, providing novel molecular insights into curd formation and identifying potential breeding targets for the genetic improvement of Brassicaceae crops. Full article
(This article belongs to the Topic Genetic Breeding and Biotechnology of Garden Plants)
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20 pages, 10831 KB  
Article
Loss of Function of the Zxdb Gene Leads to a Decrease in the Decidualization Rate and Number of Pups Born in Mice by Affecting the Expression of the Cell Adhesion Molecules
by Yafei Tian, Yang Zhang, Mengru Li, Rui Yin, Pingping Ding, Letong Liang, Bowen Chen, Rui Xu, Hongyan Chen, Chenming Xu, Songchang Chen and Daru Lu
Curr. Issues Mol. Biol. 2026, 48(2), 144; https://doi.org/10.3390/cimb48020144 - 28 Jan 2026
Viewed by 146
Abstract
The Zinc Finger X-Linked Duplicate B (ZXDB) gene is one of a pair of replicated zinc finger genes on chromosome Xp11.21. The homologous gene of ZXDB in mice is Zxdb. Recent studies have found that Zxdb plays a role in [...] Read more.
The Zinc Finger X-Linked Duplicate B (ZXDB) gene is one of a pair of replicated zinc finger genes on chromosome Xp11.21. The homologous gene of ZXDB in mice is Zxdb. Recent studies have found that Zxdb plays a role in the spermatogenic process of mice; however, its impact on the female reproductive system has not yet been explored. In our study, we found, for the first time, that the loss of function of Zxdb leads to reduced decidualization rates and a decrease in litter size in female mice. Secondly, we found that maternal loss of Zxdb is the determinant of these phenotypes. Thirdly, the transcriptional and proteomic differential expression genes in the uterine tissues of wild-type (WT) and Zxdb knockout (Zxdb-KO) mice were significantly enriched in signaling pathways such as adhesion molecules. Finally, we demonstrated that the disorder of expression and uneven distribution of adhesion molecules in mouse uterine tissue may be the main reason for the decline in embryo implantation rate. In conclusion, we have established for the first time a link between the Zxdb gene and reduced female fertility. This study will help provide guidance and genetic counseling for future common clinical complications such as Recurrent Spontaneous Abortion (RSA) or Recurrent Implantation Failure (RIF). Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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39 pages, 1762 KB  
Review
Hereditary Endometrial Cancer: Lynch Syndrome, Mismatch Repair Deficiency, and Emerging Genetic Predispositions—A Comprehensive Review with Clinical and Laboratory Guidelines
by Andrzej Kluk, Hanna Gryczka, Małgorzata Braszka, Rafał Ałtyn, Hanna Markiewicz, Jan K. Ślężak, Ewa Dwojak, Joanna Czerniak, Paweł Zieliński, Bartosz J. Płachno and Paula Dobosz
Int. J. Mol. Sci. 2026, 27(3), 1304; https://doi.org/10.3390/ijms27031304 - 28 Jan 2026
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Abstract
Endometrial cancer is the most common gynaecologic malignancy in high-income countries, with a rising incidence largely driven by reproductive factors, obesity, and prolonged exposure to unopposed oestrogens. Although most cases are sporadic, approximately 2–5% are associated with hereditary cancer syndromes, of which Lynch [...] Read more.
Endometrial cancer is the most common gynaecologic malignancy in high-income countries, with a rising incidence largely driven by reproductive factors, obesity, and prolonged exposure to unopposed oestrogens. Although most cases are sporadic, approximately 2–5% are associated with hereditary cancer syndromes, of which Lynch syndrome represents the most important contributor. Lynch syndrome results from germline mutations in DNA mismatch repair (MMR) genes and is associated with a substantially increased lifetime risk of endometrial cancer, reaching up to 71% in carriers of MutS homologue 6 (MSH6) mutations. Hereditary cancer predisposition typically follows an autosomal dominant inheritance pattern and may be suspected based on clinical warning signs such as early disease onset, multiple primary malignancies, a strong family history, or the presence of microsatellite instability in tumour tissue. In addition to Lynch syndrome, rarer genetic conditions—including Cowden syndrome (PTEN), Li–Fraumeni syndrome (TP53), polymerase proofreading–associated polyposis (POLE/POLD1), and hereditary breast and ovarian cancer syndromes (BRCA1/2)—also contribute to hereditary endometrial cancer risk. Recognition of these genetic backgrounds is essential for accurate diagnosis, personalised surveillance, and the implementation of targeted preventive and therapeutic strategies. Despite major advances in molecular diagnostics, hereditary endometrial cancer remains frequently underdiagnosed, leading to missed opportunities for cancer prevention among affected individuals and their families. This comprehensive review summarises current evidence on hereditary predispositions to endometrial cancer, with a particular emphasis on Lynch syndrome, and discusses underlying genetic mechanisms, inheritance patterns, diagnostic strategies, and clinical implications for screening, genetic counselling, and treatment optimisation. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Fourth Edition)
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