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13 pages, 386 KB  
Article
Annual Variability in Cone and Seed Yields Across Seed Stands of Taurus Cedar (Cedrus libani) and Its Impact on Gene Diversity of Seed Crops
by Kyu-Suk Kang, Marianthi Tsakaldimi and Nebi Bilir
Forests 2026, 17(4), 481; https://doi.org/10.3390/f17040481 - 14 Apr 2026
Viewed by 102
Abstract
The variation in annual cone and seed production was examined for three natural seed stands of Taurus cedar (Cedrus libani A. Rich., Pinaceae), each with distinct structural characteristics, sampled from 35 trees for three consecutive years. Fertility variation (Ψ), estimated by cone [...] Read more.
The variation in annual cone and seed production was examined for three natural seed stands of Taurus cedar (Cedrus libani A. Rich., Pinaceae), each with distinct structural characteristics, sampled from 35 trees for three consecutive years. Fertility variation (Ψ), estimated by cone (ΨC) and seed (ΨS) yields per tree, was also analyzed to contribute to the management and development of silvicultural practices for the seed stands of the species. Significant differences (p < 0.05) were recorded in cone and seed production across years, between populations, and between trees within a population. Population x year interactions were also significant (p < 0.05), highlighting the importance of seed harvesting year in cone collection. Fertility variation in cones and filled seeds showed only small deviation [ΨC = 1.10 (91% of census number)–1.71 (59%), Ψs = 1.25 (80%)–1.71 (59%)] among the seed stands in different years, except ΨS = 2.38 (42%) in a population in one year. The cone and seed fertility were at acceptable levels for an ideal natural population (Ψ ≤ 3). Figures of parental balance curves showed that the contribution to the gamete gene pool was much closer to equal for cone production across the years than for filled seed production in both individual stands and pooled stands, suggesting that the number of cones is a good indicator of overall seed production. Difference in gene diversity (GD) was 0.005 from individual year (GD = 0.992 and 0.993) to pooled years of the populations (GD = 0.997 and 0.998) for both cone and seed yields, while it was higher among years within population (e.g., 0.017 for cone yield and 0.026 for seed yield in a population). Full article
(This article belongs to the Special Issue Forest Tree Seed and Seedling Production)
21 pages, 2684 KB  
Article
RNA-Seq Analysis of Human Cumulus Cells Identifies Angiogenic Pathways Associated with Infertility
by Alejandro Baratas, Victoria Pérez-Quiroga, Rosario Planello, Mónica Aquilino, Magdalena Serrano, Moisés de la Casa, Yosu Franco-Iriarte and Rosa Roy
Cells 2026, 15(8), 677; https://doi.org/10.3390/cells15080677 - 11 Apr 2026
Viewed by 226
Abstract
Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. [...] Read more.
Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. In the present study, we performed RNA-seq on CCs from healthy oocyte donors and infertile patients, utilizing a multi-pipeline bioinformatic approach (STAR-Cufflinks, TopHat-HTSeq, and HISAT2-StringTie) to establish a high-confidence, exploratory transcriptomic profile. A set of 234 differentially expressed genes (DEGs) consistently identified across pipelines was obtained, with functional enrichment highlighting blood vessel morphogenesis and angiogenesis as primary drivers of transcriptomic divergence between groups. RT-qPCR validation in individual samples confirmed statistically significant differences for ANKRD22 (upregulated) and E2F7 (downregulated) in infertile patients, while other angiogenesis-related genes, including ANGPT1, ANGPT2 and THBS1, showed consistent but non-significant expression trends, suggesting alterations in angiogenesis-related processes within the follicular microenvironment. These findings support the presence of coordinated angiogenesis-related alterations in cumulus cells and provide a basis for future studies exploring their potential relevance in oocyte competence and ART outcomes. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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17 pages, 1487 KB  
Review
Nutritional Regulation of Reproductive Physiology in Ruminants: A Mechanistic Review
by Ting-Chieh Kang, Geng-Jen Fan, Hisn-Hung Lin, Kai-Fei Tseng, Ya-Chun Liu and Hsi-Hsun Wu
Life 2026, 16(4), 630; https://doi.org/10.3390/life16040630 - 8 Apr 2026
Viewed by 344
Abstract
Modern genetic selection for high productivity has created a physiological conflict in ruminants, where the metabolic demands of lactation compete directly with the energy requirements of reproduction. This review provides a mechanistic synthesis of how key nutritional factors modulate the endocrine and cellular [...] Read more.
Modern genetic selection for high productivity has created a physiological conflict in ruminants, where the metabolic demands of lactation compete directly with the energy requirements of reproduction. This review provides a mechanistic synthesis of how key nutritional factors modulate the endocrine and cellular pathways governing reproductive success in cattle and sheep. Negative energy balance (NEB), characteristic of the early postpartum period, suppresses the hypothalamic–pituitary–gonadal (HPG) axis by impairing the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), mediated through reduced kisspeptin signaling, growth hormone (GH) resistance, and decreased circulating insulin, insulin-like growth factor-1 (IGF-1), and leptin. At the macronutrient level, excess rumen-degradable protein elevates blood urea nitrogen and impairs the uterine environment, while omega-3 polyunsaturated fatty acids inhibit prostaglandin F2α synthesis to support corpus luteum maintenance. At the micronutrient level, selenium, copper, and zinc are essential antioxidant cofactors protecting gametes and embryos from oxidative stress, while vitamins A, D, and E regulate gene expression in reproductive tissues. Furthermore, maternal nutrition during critical gestational windows programs the reproductive capacity of offspring through epigenetic modifications, with profound implications for long-term herd fertility. Understanding these nutritional–reproductive interactions is crucial for developing precision feeding strategies that optimize herd fertility, improve animal welfare, and ensure the economic sustainability of livestock management. A thorough understanding of these nutritional–reproductive interactions is essential for developing precision feeding strategies that optimize fertility in high-producing ruminants. Full article
(This article belongs to the Special Issue Perspectives on Nutrition and Livestock Health)
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12 pages, 6824 KB  
Communication
Derivation of Embryonic Stem Cells from an Endangered Cattle Breed via Somatic Cell Nuclear Transfer
by Shigang Gu, Xinhua Wei, Yurong Zhang, Jinqian Wang, Lu Tang, Wenxuan Zhao, Jing Wang and Yongye Huang
Cells 2026, 15(7), 627; https://doi.org/10.3390/cells15070627 - 31 Mar 2026
Viewed by 366
Abstract
Embryonic stem cells represent a valuable germplasm resource with significant implications for breed conservation, development, and utilization. However, the scarcity of genetic resources in endangered species poses a fundamental constraint on obtaining gametes for embryonic stem cell derivation. Therefore, generating embryonic stem cells [...] Read more.
Embryonic stem cells represent a valuable germplasm resource with significant implications for breed conservation, development, and utilization. However, the scarcity of genetic resources in endangered species poses a fundamental constraint on obtaining gametes for embryonic stem cell derivation. Therefore, generating embryonic stem cells from somatic cell nuclear transfer blastocysts offers an optimal alternative for conservation cloning. In this study, we established ApèiJiaza somatic cell nuclear transfer ESCs (APNT-ESCs) from cloned embryos, using ApèiJiaza cattle ear fibroblasts as nuclear donors. APNT-ESCs could be passaged for over 30 generations in vitro, exhibiting high expression of key pluripotency markers, genomic stability, and the ability to form embryoid bodies and differentiate into cell types of all three germ layers. This research established an effective biotechnological framework for the genetic conservation of other endangered species lacking accessible gametes. Full article
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17 pages, 1932 KB  
Review
Nanoparticle-Based Approaches for Enhancing In Vitro Fertilization in Animal Reproduction
by Elżbieta Gałęska, Alicja Kowalczyk, Marko Samardžija, Gordana Gregurić Gračner, Marcjanna Wrzecińska, Jose Pedro Araujo, José Ángel Hernández Malagón, Mercedes Camiña, Ewa Czerniawska-Piątkowska and Zbigniew Dobrzański
Int. J. Mol. Sci. 2026, 27(6), 2747; https://doi.org/10.3390/ijms27062747 - 18 Mar 2026
Viewed by 454
Abstract
Nanotechnology, based on nanoparticles, has become an emerging interdisciplinary tool in reproductive biotechnology, offering innovative opportunities to improve fertilization efficiency and reproductive performance in farm animals. The purpose of this review is to provide an updated synthesis of current research on nanoparticle-based approaches [...] Read more.
Nanotechnology, based on nanoparticles, has become an emerging interdisciplinary tool in reproductive biotechnology, offering innovative opportunities to improve fertilization efficiency and reproductive performance in farm animals. The purpose of this review is to provide an updated synthesis of current research on nanoparticle-based approaches that enhance in vitro fertilization outcomes and other assisted reproductive technologies. The focus is on the biological mechanisms, potential benefits, and limitations of nanoparticle use in animal reproduction. Nanoparticles—including gold, silver, zinc oxide, selenium, and magnetic iron oxide—exhibit distinctive physicochemical properties that enable targeted interactions with gametes and reproductive cells. When used in semen extenders or culture media, nanoparticles improve sperm motility, acrosome and membrane integrity, and reduce oxidative stress and apoptosis. These effects contribute to enhanced fertilization rates and higher embryo developmental competence. In addition, nanoparticles can function as carriers for hormones, antioxidants, and growth factors, stabilizing reagents essential for oocyte maturation, sperm capacitation, and early embryo culture. The review also discusses nanopurification (selectively isolating and removing particles) and nanosorting (separating or organizing nanoscale objects) techniques that allow for non-invasive selection of viable gametes, and fluorescence- and magnet-assisted sorting systems that increase precision in sperm sexing. The mechanical aspects of nanoparticle–cell interactions are analyzed, emphasizing the influence of particle size, dose, and surface modification on both biological efficacy and cytotoxicity. Safety, toxicological concerns, and regulatory frameworks—including International Organization for Standardization (ISO) standards and European Commission recommendations—are critically reviewed to highlight the need for harmonized biocompatibility criteria. Although nanoparticle use in animal reproduction remains largely experimental, accumulated evidence demonstrates its potential to improve reproductive efficiency and reduce economic losses. Integrating nanoparticle-based systems with existing reproduction platforms may represent a transformative step toward sustainable and precision-driven livestock breeding. Full article
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14 pages, 4121 KB  
Article
Reproductive Cycle Dynamics of Subtropical Manila Clams (Ruditapes philippinarum) Cultured in Temperate Waters: Temperature Thresholds and Bimodal Spawning Patterns
by Wei Guo, Ling Guo, Xujing Liang, Yangyang He, Xiwu Yan, Shuang Liang and Jian Liang
Fishes 2026, 11(3), 177; https://doi.org/10.3390/fishes11030177 - 17 Mar 2026
Viewed by 308
Abstract
The Manila clam Ruditapes philippinarum is a commercially important bivalve worldwide, with China being the leading producer. While the reproductive biology of this species has been extensively studied in its native or long-established ranges, knowledge of how populations cultured from non-native seed sources [...] Read more.
The Manila clam Ruditapes philippinarum is a commercially important bivalve worldwide, with China being the leading producer. While the reproductive biology of this species has been extensively studied in its native or long-established ranges, knowledge of how populations cultured from non-native seed sources adapt their reproductive cycles to new environmental conditions remains limited. In this observational study, we investigated the annual reproductive cycle of a Manila clam population originating from subtropical waters (Zhejiang Province, Southern China) that was cultured in temperate aquaculture grounds in Zhuanghe Bay, Northern China. Monthly histological examination of 50 clams demonstrated that the gametogenic cycle synchronized between male and female clams. Gametogenesis started in March when seawater temperature exceeded 5.7 °C, and most gametes matured by May. A distinct bimodal spawning pattern was observed: a minor spawning event occurred from May to July, followed by a major spawning phase from September to November after a one-month gonadal recovery period in August. The condition index (CI), analyzed monthly in 30 clams, effectively reflected reproductive stages, increasing during gametogenesis and declining sharply during spawning, with its amplitude indicating spawning intensity. Seawater temperature was identified as the primary regulatory factor driving reproductive development from gametogenesis to spawning, while food availability (indicated by chlorophyll a concentration) played a crucial role in supporting gonadal recovery during summer. These results align with observations in other temperate populations, demonstrating that subtropical-origin clams can successfully acclimate their reproductive cycles to temperate environmental conditions. This study provides the first comprehensive description of the reproductive biology of transplanted Manila clams in Northern China, offering critical benchmarks for optimizing hatchery production schedules and informing sustainable fishery management practices in the region. Full article
(This article belongs to the Special Issue Biology and Culture of Marine Invertebrates)
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2 pages, 165 KB  
Abstract
Modulation of Antioxidant Pathway by Bioactive Peptides: Impact on Post-Thaw Sperm Viability and Motility
by Bruno S. Sá, Ana Gabriela P. Meneses, Sophia A. dos Reis, Natália P. B. Valadares, João B. Nunes, Pedro Paulo R. C. Melo, Andreanne G. Vasconcelos and José Roberto S. A. Leite
Proceedings 2026, 137(1), 90; https://doi.org/10.3390/proceedings2026137090 - 4 Mar 2026
Viewed by 252
Abstract
Introduction: Sperm cryopreservation is a crucial advancement for fertility preservation—whether for social or clinical medical reasons—allowing for the postponement of gamete use and favoring reproductive planning [...] Full article
(This article belongs to the Proceedings of The 6th International Congress on Health Innovation—INOVATEC 2025)
18 pages, 1793 KB  
Article
Pyrroloquinoline Quinone Alleviates Tris(1,3-Dichloro-2-Propyl) Phosphate-Induced Damage During Mouse Oocyte Maturation
by Lichen Sun, Zhihong Cao, Linli Xiao, Jiahua Bai, Kexiong Liu, Yusheng Qin, Yan Liu and Xiaoling Xu
Animals 2026, 16(4), 673; https://doi.org/10.3390/ani16040673 - 21 Feb 2026
Viewed by 481
Abstract
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a ubiquitous organophosphate flame retardant posing potential threats to reproductive health. Given that TDCIPP toxicity is often linked to oxidative stress, pyrroloquinoline quinone (PQQ), a potent natural antioxidant and mitochondrial nutrient, was hypothesized to mitigate these adverse effects. This [...] Read more.
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a ubiquitous organophosphate flame retardant posing potential threats to reproductive health. Given that TDCIPP toxicity is often linked to oxidative stress, pyrroloquinoline quinone (PQQ), a potent natural antioxidant and mitochondrial nutrient, was hypothesized to mitigate these adverse effects. This study investigated the impact of TDCIPP exposure on the in vitro maturation of mouse oocytes and evaluated the protective role of PQQ. Using an in vitro maturation model, we assessed the toxic effects of TDCIPP by examining the first polar body extrusion (PBE) rate and cumulus expansion, followed by analyses of oxidative stress (ROS and GSH), mitochondrial integrity (ATP content and distribution), and apoptosis-related markers through transcriptome sequencing (Smart RNA-seq), quantitative real-time PCR, and immunofluorescence. The results demonstrated that TDCIPP significantly suppressed cumulus expansion and reduced the PBE rate. Mechanistically, TDCIPP induced severe oxidative stress, disrupted mitochondrial function, and activated the apoptotic pathway. Furthermore, TDCIPP triggered early apoptotic signaling by downregulating Bcl-2 and upregulating Bax. Notably, supplementation with PQQ effectively reversed these detrimental effects by reducing intracellular ROS levels, maintaining GSH content, preserving mitochondrial density and ATP production, and inhibiting apoptosis. In conclusion, our findings provide new insights into the gamete toxicity of TDCIPP and suggest that PQQ may serve as a potential therapeutic agent to protect oocyte quality against environmental pollutant-induced damage. Full article
(This article belongs to the Section Animal Reproduction)
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17 pages, 3366 KB  
Article
Hemp Meal (Cannabis sativa) as an Alternative Dietary Protein Source for European Perch (Perca fluviatilis)
by Wiktoria Cieśla, Dobrochna Adamek-Urbańska, Robert Kasprzak, Piotr Gomułka, Maciej Wójcik, Joanna Bochenek, Helena Bober, Kacper Kawalski, Jakub Martynow, Adrian Szczepański, Hubert Szudrowicz, Małgorzata Woźniak, Jerzy Śliwiński, Katarzyna Palińska-Żarska, Daniel Żarski, Sławomir Krejszeff, Jarosław Król and Maciej Kamaszewski
Animals 2026, 16(4), 649; https://doi.org/10.3390/ani16040649 - 18 Feb 2026
Viewed by 568
Abstract
The production of European perch (Perca fluviatilis) has become notably refined, with numerous physiological and nutritional studies conducted in recent years. However, it is still an expensive undertaking due to the high amount of animal protein required in the feed. Therefore, [...] Read more.
The production of European perch (Perca fluviatilis) has become notably refined, with numerous physiological and nutritional studies conducted in recent years. However, it is still an expensive undertaking due to the high amount of animal protein required in the feed. Therefore, we investigated the possibility of using hemp meal (HM) as an alternative source of protein in extruded feed for perch reared in recirculating aquaculture systems (RASs). Perch fry (initial body weight of 68.1 g) was divided into four groups (HM0, HM10, HM20, HM30; 100 fish in each) and fed with diets containing different levels of HM (0, 10, 20 or 30%, respectively) for 10 weeks. Overall, dietary inclusion of HM did not affect body parameters, muscle composition, or blood parameters, nor did it cause any serious histopathological lesions. Nonetheless, basic production indices (SGR, FCR, PER) all peaked in the HM20 group, and predominantly positive changes in intestinal mucosa were found in all three HM-inclusion groups. Furthermore, the expression patterns of several genes in the intestine and liver were different in groups HM20-30 than in HM0-10. Lastly, hepatic activities of alkaline phosphatase (ALP) and glutathione peroxidase (GPX) diminished with increasing dietary HM inclusion levels. In summary, there were no negative effects of HM on the homeostasis of studied fish or, more specifically, the physiology of their digestive organs. When accounting for minor tendencies in the results, the dietary inclusion of hemp meal at 20% turned out to be the most promising fish meal alternative for the European perch. Full article
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21 pages, 2078 KB  
Article
Comparative Proteomic Analysis of Gonadal Tissue in Solea senegalensis Reveals Reproductive Deregulation Associated with F1 Individuals
by Marco Anaya-Romero, Alberto Arias-Pérez, María Esther Rodríguez, Manuel Alejandro Merlo, Silvia Portela-Bens, Ismael Cross and Laureana Rebordinos
Biomolecules 2026, 16(2), 312; https://doi.org/10.3390/biom16020312 - 16 Feb 2026
Cited by 1 | Viewed by 614
Abstract
Reproductive dysfunction in captive-bred Senegalese sole (Solea senegalensis) limits aquaculture production consolidation, particularly due to reduced fertility and poor sperm quality in F1 males. To elucidate the molecular mechanisms underlying this problem, a quantitative proteomic analysis was conducted using LC–MS/MS on [...] Read more.
Reproductive dysfunction in captive-bred Senegalese sole (Solea senegalensis) limits aquaculture production consolidation, particularly due to reduced fertility and poor sperm quality in F1 males. To elucidate the molecular mechanisms underlying this problem, a quantitative proteomic analysis was conducted using LC–MS/MS on gonadal tissues from wild and F1 males and females. A total of 2221 proteins were identified, of which 1797 were retained after quality filtering. Comparative analyses revealed clear segregation by origin (F1 [cultivated] and wild) and sex (male and female), and 86 proteins were differentially expressed between F1 and wild males. Functional enrichment showed significant downregulation of key reproductive processes in F1 males, including sperm–egg recognition, binding of sperm to zona pellucida, and acrosome reaction, suggesting impaired gamete interaction and fertilization ability. Conversely, F1 males displayed metabolic and proteolytic pathway enrichment, which is indicative of compensatory energy demands. Protein–protein interaction network analysis identified a reproductive subnetwork dominated by zona pellucida sperm-binding proteins, which exhibited reduced connectivity in F1 males. These results demonstrate a coordinated suppression of molecular components essential for sperm–egg communication and acrosomal exocytosis, providing proteomic evidence for the systemic deregulation of the reproductive machinery in F1 fish. This study identifies potential protein biomarkers linked to reproductive performance, offering molecular targets to improve broodstock management and fertilization success in S. senegalensis aquaculture. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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19 pages, 1029 KB  
Review
Functional Changes in the Fallopian Tube: Environmental Factors, Lifestyle, Pathological Conditions and Pharmacological Agents
by Opalina Roy, Sandhya Kumari, Satish Kumar Adiga, Manjunath B. Joshi, Anujith Kumar, Ganesh Venkatraman, Nagarajan Kannan and Guruprasad Kalthur
Cells 2026, 15(3), 269; https://doi.org/10.3390/cells15030269 - 31 Jan 2026
Viewed by 997
Abstract
The fallopian tubes are critical segments of the female reproductive tract and are essential for transporting gametes and embryos. It creates a conducive environment necessary for successful fertilization, early embryo development, and embryo transport. The cellular composition and function of the fallopian tube [...] Read more.
The fallopian tubes are critical segments of the female reproductive tract and are essential for transporting gametes and embryos. It creates a conducive environment necessary for successful fertilization, early embryo development, and embryo transport. The cellular composition and function of the fallopian tube are tightly regulated by the sex hormones estradiol and progesterone. Therefore, any pathological/ metabolic condition or exposure to exogenous agents with the potential to alter endocrine levels can have a significant impact on fallopian tube function and health. This review summarizes the effects of medications, infections, pathological conditions, lifestyle choices, and environmental factors that can significantly impact the morphology, histology, cellularity, and functionality of the fallopian tube. Full article
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35 pages, 4952 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 683
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)
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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
Cited by 1 | Viewed by 987
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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15 pages, 1310 KB  
Article
Effects of Caffeic Acid Supplementation on Human Sperm Against In Vitro-Induced Oxidative Stress: Nrf2 Molecular Pathway
by Laura Liguori, Cinzia Signorini, Giulia Collodel, Caterina Marcucci and Elena Moretti
Antioxidants 2026, 15(1), 133; https://doi.org/10.3390/antiox15010133 - 20 Jan 2026
Viewed by 646
Abstract
Oxidative stress (OS) is a major cause of defective sperm function. During laboratory handling, gametes are exposed to OS, potentially mitigated by in vitro antioxidant supplementation. This study evaluates the protective role of caffeic acid (CAF) on basal human semen and under induced [...] Read more.
Oxidative stress (OS) is a major cause of defective sperm function. During laboratory handling, gametes are exposed to OS, potentially mitigated by in vitro antioxidant supplementation. This study evaluates the protective role of caffeic acid (CAF) on basal human semen and under induced OS. First, six semen samples from normozoospermic donors were incubated with CAF concentrations ranging from 50 to 500 µM at 37 °C for 2 h. Sperm motility and DNA integrity (acridine orange) were evaluated. Then, ten semen samples were divided into four aliquots and incubated, respectively, with CAF at 100 µM, H2O2 at 2 mM, or H2O2 at 2 mM + CAF at 100 µM, or untreated. Motility, DNA integrity, acrosome status (Pisum sativum agglutinin), OS quantified by F2-isoprostanes (ELISA), and expression of Nrf2, Keap1, and HO-1 (qRT-PCR) were assessed. CAF at 100 µM improved progressive motility without damaging DNA and was selected for subsequent experiments. CAF showed protective effects on sperm damage induced by H2O2 treatment, restoring motility, DNA integrity, and acrosome status and reducing F2-isoprostane levels. Nrf2 and HO-1 expression were upregulated by CAF, downregulated by H2O2, and restored by the co-treatment. CAF supplementation may protect human spermatozoa during in vitro handling by reducing OS, improving several sperm parameters, with a possible mechanism of action involving the Nrf2 pathway. Full article
(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)
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31 pages, 3317 KB  
Review
Reactive Oxygen Species in Embryo Development: Sources, Impacts, and Implications for In Vitro Culture Systems
by Sajuna Sunuwar and Yun Seok Heo
Life 2026, 16(1), 136; https://doi.org/10.3390/life16010136 - 15 Jan 2026
Cited by 2 | Viewed by 1255
Abstract
Reactive oxygen species (ROS) are essential regulators of fertilization and early embryo development in mammals, including humans and various animal models, but they exert detrimental effects when produced in excess. In assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), exposure to non-physiological [...] Read more.
Reactive oxygen species (ROS) are essential regulators of fertilization and early embryo development in mammals, including humans and various animal models, but they exert detrimental effects when produced in excess. In assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), exposure to non-physiological conditions increases oxidative stress (OS), impairing gamete quality, embryo viability, and clinical outcomes. This review synthesizes experimental and clinical studies describing the endogenous and exogenous sources of ROS relevant to embryo development in IVF. Endogenous ROS arise from intrinsic metabolic pathways such as oxidative phosphorylation, NADPH oxidase, and xanthine oxidase. Exogenous sources include suboptimal laboratory conditions characterized by factors such as high oxygen tension, temperature shifts, pH instability, light exposure, media composition, osmolarity, and cryopreservation procedures. Elevated ROS disrupt oocyte fertilization, embryonic cleavage, compaction, blastocyst formation, and implantation by inducing DNA fragmentation, lipid peroxidation, mitochondrial dysfunction, and apoptosis. In addition, the review highlights how parental health factors establish the initial redox status of gametes, which influences subsequent embryo development in vitro. While antioxidant supplementation and optimized culture conditions can mitigate oxidative injury, the precise optimal redox environment remains a subject of ongoing research. This review emphasizes that future research should focus on defining specific redox thresholds and developing reliable, non-invasive indicators of embryo oxidative status to improve the success rates of ART. Full article
(This article belongs to the Special Issue Advances in Livestock Breeding, Nutrition and Metabolism)
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