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Search Results (2,024)

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Keywords = reproductive physiology

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27 pages, 2390 KB  
Article
Whole-Transcriptome Profiling of Ovarian Tissues in Gilts with Normal Estrus and Follicular Cyst-Associated Anestrus
by Lingyan Lv, Jiaqing Zhang, Xianhua Wu, Changhua Lin, Yangzu Zhang, Hongfang Mo, Jiapeng Li, Xun Li, Jiaming Zheng and Chuanhuo Hu
Int. J. Mol. Sci. 2026, 27(15), 6848; https://doi.org/10.3390/ijms27156848 - 30 Jul 2026
Abstract
We explored the potential functions of differentially expressed miRNAs, mRNAs, lncRNAs, and circRNAs identified in the ovaries of gilts with normal estrus (NE) and follicular cyst-associated anestrus (AE), as well as their putative competing endogenous RNA (ceRNA) regulatory networks. Ovarian morphology was assessed [...] Read more.
We explored the potential functions of differentially expressed miRNAs, mRNAs, lncRNAs, and circRNAs identified in the ovaries of gilts with normal estrus (NE) and follicular cyst-associated anestrus (AE), as well as their putative competing endogenous RNA (ceRNA) regulatory networks. Ovarian morphology was assessed via ultrasonography, and serum concentrations of Follicle-stimulating hormone (FSH), (Estradiol) E2, and Progesterone(P4) were measured. Ovarian tissues were harvested after slaughter for whole-transcriptome sequencing. Bioinformatic tools were used to screen differentially expressed RNAs(DERNAs) between NE and AE gilts. We further predicted target interactions among these transcripts, conducted functional enrichment analysis on target genes, and constructed candidate ceRNA regulatory networks potentially associated with gilt estrus. Phenotypic verification confirmed that ovarian ultrasonographic characteristics, histological morphology, and serum reproductive hormone levels were consistent with the physiological status of NE and AE gilts. Under the screening thresholds of p < 0.05 and |log2FC| ≥ 1, we identified 22 lncRNAs that may interact with 21 mRNAs via 50 miRNAs, alongside 39 circRNAs predicted to regulate 26 mRNAs through 72 miRNAs. Functional enrichment analysis indicated that target genes of these differentially expressed transcripts were predominantly enriched in the lysosome pathway, PPAR signaling pathway, chemokine signaling pathway, cholesterol metabolism and NOD-like receptor signaling pathway. Hub molecules including FGF1, GHR, TLR2, ssc-miR-370, and miR-21-5p were shared in lncRNA/circRNA-miRNA-mRNA regulatory networks; these molecules have been reported to participate in progesterone synthesis, estrus modulation, and endocrine homeostasis. Of particular interest, two non-coding RNAs, MSTRG.1285.1 and novel_circ_056113, were predicted to act as candidate ceRNAs that may sponge ssc-miR-370 and miR-21-5p, which could in turn modulate the expression of estrus-associated mRNAs including FGF1, GHR, and TLR2. The expression trends of MSTRG.1285.1, novel_circ_056113, miR-370, miR-21-5p, GHR, TLR2, and FGF1 were validated by qRT-PCR, and the quantification results agreed with transcriptome sequencing data. Collectively, this study constructed a predicted ceRNA regulatory network of ovarian transcripts comparing NE and AE gilts and uncovered multiple RNA molecules potentially involved in estrus regulation. These findings offer preliminary theoretical clues for exploring the onset of puberty in gilts. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Animal Genetics and Genomics)
16 pages, 1760 KB  
Review
Iron-Sulfur Clusters: A Core Hub in Insect Energy, Reproduction, and Molting
by Xiao-Han Di, Shuo Liu, Duo Wang and Jing-Ze Liu
Insects 2026, 17(8), 791; https://doi.org/10.3390/insects17080791 - 29 Jul 2026
Abstract
Iron-sulfur clusters are a class of functionally diverse protein cofactors. In recent years, significant progress has been made in insect research on iron-sulfur clusters, revealing that they serve as a core molecular hub that integrate multiple physiological processes. This review systematically summarizes the [...] Read more.
Iron-sulfur clusters are a class of functionally diverse protein cofactors. In recent years, significant progress has been made in insect research on iron-sulfur clusters, revealing that they serve as a core molecular hub that integrate multiple physiological processes. This review systematically summarizes the structural characteristics and biosynthetic pathways of iron-sulfur clusters, with an emphasis on insect-specific features in the stability of iron-sulfur cluster assembly proteins, cluster transfer mechanisms, and functional differentiation of ferredoxins. On this basis, it further elucidates the central roles of insect iron-sulfur clusters in energy homeostasis, reproductive capacity, ecdysis, detoxification metabolism, and magnetoreception, and revealed the potential regulatory mechanisms of iron–sulfur proteins in the aforementioned physiological processes in insects, including the electron transport chain, the tricarboxylic acid cycle, the AMPK/TOR signaling axis, cell cycle regulation, and P450 enzyme activity. These findings provide important theoretical foundations and potential molecular targets for the development of environmentally friendly pest control strategies with low resistance risk. Full article
(This article belongs to the Section Insect Physiology, Reproduction and Development)
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31 pages, 1544 KB  
Review
From Prenatal Exposure to Adult Sexual Dysfunction: The Impact of Plastic-Derived Endocrine Disruptors on Testosterone Homeostasis and Erectile Function
by Sofoklis Stavros, Panagiotis Christopoulos, Eriketi Kokkosi, Efthalia Moustakli, Athanasios Zikopoulos, Anastasios Potiris, Maria Anastasia Daskalaki, Ioannis Arkoulis, Ismini Anagnostaki, Ioanna Vassilaki, Nikolaos Kathopoulis, George Daskalakis and Peter Drakakis
Toxics 2026, 14(8), 673; https://doi.org/10.3390/toxics14080673 - 29 Jul 2026
Abstract
Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to [...] Read more.
Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes. Full article
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20 pages, 3177 KB  
Article
Generation of Functional GnRH-Responsive Pituitary-like Organoids from Ovine Embryonic Stem Cells
by Hua Yang, Hui Xu, Wenli Lv, Yu Cai, Shanglai Li, Yongjie Wan, Jakree Jitjumnong, Xiaojuan Luo, Feng Wang and Yanli Zhang
Cells 2026, 15(15), 1360; https://doi.org/10.3390/cells15151360 - 28 Jul 2026
Abstract
The pituitary gland is a master regulator of endocrine and reproductive physiology; however, the lack of physiologically relevant in vitro models in livestock species has limited studies of pituitary development and endocrine function. Although pituitary organoids have been generated from human and mouse [...] Read more.
The pituitary gland is a master regulator of endocrine and reproductive physiology; however, the lack of physiologically relevant in vitro models in livestock species has limited studies of pituitary development and endocrine function. Although pituitary organoids have been generated from human and mouse pluripotent stem cells, comparable models remain unavailable in large animal species. Here, we established functional pituitary-like organoids from ovine embryonic stem cells (oESCs) using a three-dimensional differentiation strategy. The resulting organoids self-organized into Rathke’s pouch-like structures and acquired pituitary progenitor characteristics, as demonstrated by the robust expression of LHX3, PITX1, ISLET1 and PROP1. Compared with conventional two-dimensional differentiation, the organoids displayed enhanced structural organization and improved lineage specification. Notably, the organoids exhibited functional gonadotroph maturation, with GnRH treatment significantly upregulating FSHB and LHB expression, as confirmed by immunohistochemistry, qPCR and Western blot. SMART-Seq transcriptome analysis revealed progressive loss of pluripotency-associated signatures and activation of pituitary developmental programs, including sustained expression of lineage-associated regulators such as PAX6. Collectively, this study establishes the first ovine pituitary-like organoid model and demonstrates its capacity to generate functional GnRH-responsive gonadotroph cells. This platform provides a valuable resource for investigating pituitary development, reproductive endocrinology, livestock fertility, and endocrine disease mechanisms in a large-animal context. Full article
(This article belongs to the Section Stem Cells)
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28 pages, 2401 KB  
Review
Postpartum Uterine Diseases in Dairy Cattle: Integrating Microbiology, Immunology, and Reproductive Physiology
by Ramanathan Kasimanickam, Priunka Bhowmik and Zhihua Jiang
Microorganisms 2026, 14(8), 1645; https://doi.org/10.3390/microorganisms14081645 - 28 Jul 2026
Abstract
Postpartum uterine diseases are among the most prevalent and economically important reproductive disorders affecting dairy cattle worldwide. These conditions, including metritis, clinical and subclinical endometritis, and pyometra, develop during the postpartum transition period when physiological, metabolic, endocrine, and immunological adaptations increase susceptibility to [...] Read more.
Postpartum uterine diseases are among the most prevalent and economically important reproductive disorders affecting dairy cattle worldwide. These conditions, including metritis, clinical and subclinical endometritis, and pyometra, develop during the postpartum transition period when physiological, metabolic, endocrine, and immunological adaptations increase susceptibility to microbial invasion and persistent uterine inflammation. Although bacterial contamination of the postpartum uterus is nearly universal, healthy cows generally restore uterine homeostasis through coordinated immune responses, microbial regulation, and effective uterine involution. Failure of these defense mechanisms results in microbial dysbiosis, impaired endometrial repair, reduced fertility, and substantial economic loss. Major pathogens associated with postpartum uterine disease include Escherichia coli, Trueperella pyogenes, Fusobacterium necrophorum, Prevotella spp., and other anaerobic bacteria that interact synergistically to promote inflammation, tissue damage, and reproductive dysfunction. Advances in next-generation sequencing, metagenomics, and metatranscriptomics have transformed understanding of the postpartum uterine microbiota and host–microbe interactions involved in disease pathogenesis. This review synthesizes current evidence regarding uterine physiology, microbial ecology, immune regulation, virulence mechanisms, dysbiosis, diagnostic approaches, and emerging omics-based technologies relevant to postpartum uterine disease in dairy cattle. Particular emphasis is placed on the ecological and physiological interactions linking microbial succession, endocrine recovery, metabolic stress, and immune competence during the postpartum period. The review further discusses translational opportunities for precision diagnostics, microbiome-informed interventions, antimicrobial stewardship, and integrated herd management strategies to improve reproductive efficiency, animal welfare, and dairy herd sustainability. Full article
(This article belongs to the Section Veterinary Microbiology)
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44 pages, 13789 KB  
Review
Integrated Drought Resilience in Foxtail Millet: From Molecular Regulation and Multi-Omics to Climate-Resilient Breeding
by Gan Liu, Shaohua Li, Qi He, Chirui Zhang, Jun Zhang and Zhong Tang
Water 2026, 18(15), 1823; https://doi.org/10.3390/w18151823 - 27 Jul 2026
Viewed by 229
Abstract
Climate change and the increasing frequency of extreme temperatures pose severe threats to global agricultural productivity, making the breeding of water-efficient crops a critical imperative. Originating from arid regions, foxtail millet serves as an ideal C4 model crop for elucidating plant adaptations to [...] Read more.
Climate change and the increasing frequency of extreme temperatures pose severe threats to global agricultural productivity, making the breeding of water-efficient crops a critical imperative. Originating from arid regions, foxtail millet serves as an ideal C4 model crop for elucidating plant adaptations to water deficits. Unlike previous reviews that often isolate genomic features from physiological responses, this review constructs an explicit conceptual framework integrating cross-scale defense mechanisms—mechanistically linking molecular signal transduction and post-transcriptional regulation to cellular homeostasis and field-scale yield stability. We first detail the developmental stage-specific physiological penalties of water stress and dissect proactive water-conservation strategies, including stomatal anatomical optimization, root-carbon reallocation, and dynamic rhizosphere remodeling. At the genetic level, we highlight the application of dynamic quantitative trait loci (QTL) mapping, which transcends the static limitations of conventional QTLs by capturing the spatiotemporal evolution of drought-tolerance traits across distinct developmental nodes. To bridge the gap between intrinsic genetic potential and field application, we spotlight the emerging integration of machine learning-assisted breeding and genomic prediction for the efficient evaluation of superior germplasms. Across this framework, several persistent gaps emerge: most drought-responsive genes identified in foxtail millet remain at the level of expression association without functional validation; dynamic QTL analysis remains underutilized relative to its capacity to resolve reproductive-stage drought tolerance; and ML-based genomic prediction, though demonstrated in this species, has not been integrated into operational breeding. Closing these gaps will require connecting high-throughput field phenotyping to genomic selection and deploying functionally validated editing targets in genetic backgrounds relevant to dryland production. Full article
(This article belongs to the Special Issue Resilient Water Management in Arid and Semi-Arid Agroecosystems)
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17 pages, 1178 KB  
Article
Study on the Effects of Feeding and Starvation on the External Morphology and Gonadal Development of Artificially Matured American Eel
by Lan Wang, Jialun Liu, Zhongmei Yang, Tongxi Ai, Feng Zhao, Keji Jiang, Lei Gao, Mingfei Li, Ye Ding, Na Zhao, Wei Jiang, Xinhui Wei, Jiayuan Xu, Jianyi Liu and Yane Yin
Fishes 2026, 11(8), 438; https://doi.org/10.3390/fishes11080438 - 24 Jul 2026
Viewed by 150
Abstract
The aim of this study is to investigate how external nutrient supply affects the allocation of reproductive energy during artificial ripening of American eels (Anguilla rostrata), as well as the physiological regulatory mechanisms involved in their bodies. Healthy female American eels [...] Read more.
The aim of this study is to investigate how external nutrient supply affects the allocation of reproductive energy during artificial ripening of American eels (Anguilla rostrata), as well as the physiological regulatory mechanisms involved in their bodies. Healthy female American eels were selected for the experiment and randomly divided into two groups: feeding group and starvation group (simulating the natural migration of American eels without eating). The initial weight of the feeding group was (308.43 ± 36.99 g), and the initial weight of the starvation group was (291.67 ± 63.31 g). The entire experiment was divided into two stages: the first stage was a 6-month nutritional reinforcement period, during which the feeding group was regularly fed with Vannamei shrimp, while the starvation group was not fed throughout the entire process. The second stage was a 3-month artificial ripening stage, during which both groups of eels stopped feeding. Inject 1 mL of mixed hormone (containing 6.5 mg of carp pituitary extract CPE+200 IU human chorionic gonadotropin HCG per mL per week) into each eel for a total of 12 injections to induce gonadal maturation. Both groups of eels did not die during the experiment, with a survival rate of 100%. As the gonads continue to develop and mature, the growth and development advantages of the feeding group of eels are very obvious: body weight, chest circumference, and gonadal index are significantly higher than those of the starvation group. After completing 12 hormone injections, the gonadal index of the feeding group reached (32.72 ± 7.01%), while that of the starvation group was only (4.35 ± 2.48%). Under artificial ripening conditions, the egg diameter of the feeding-eel group increased rapidly in the later stage of the experiment. The growth rate of eggs in the starvation group was slow, and the final egg diameter was significantly smaller. The diameters of the nuclei of both groups of oocytes increased synchronously with the progress of the experiment; the number of nucleoli in the feeding group first increased and then decreased, while the number of nucleoli in the starvation group continued to increase. The oil droplets inside both sets of eggs gradually increased in size, and the oil droplets fed to the eggs in the middle and late stages of maturation had a larger volume. Hormone test results showed that the testosterone (T) level in the eel fed group increased significantly in the later stage of the experiment. This indicates that adequate nutrition can alleviate the inhibition of the reproductive endocrine axis through positive feedback regulation of the pituitary gonad (BPG) axis. Nutritional reinforcement before ripening can promote gonadal development and enhance reproductive capacity by regulating the distribution of nutrients between muscles and gonads. The results of this study provide a solid theoretical basis for improving the nutritional management plan for parent fish in the fully artificial breeding process of American eels. Full article
(This article belongs to the Special Issue Effects of Dietary Ingredients on Fish Nutrition and Health)
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19 pages, 1017 KB  
Review
Mechanisms of Hypertension in Women: Interactions Between Vascular Ageing, Metabolic Dysfunction, and Hormonal Regulation
by Shiva Hooshmandi, Nicholas S. Freestone and Francesca I. F. Arrigoni
Biomedicines 2026, 14(8), 1667; https://doi.org/10.3390/biomedicines14081667 - 24 Jul 2026
Viewed by 320
Abstract
Purpose: Hypertension in women is a dynamic, hormone sensitive condition shaped by cumulative physiological changes across the life course. This review summarises current evidence relating vascular ageing, hormonal regulation, metabolic dysfunction, and reproductive history to blood pressure regulation in women. Materials and Methods: [...] Read more.
Purpose: Hypertension in women is a dynamic, hormone sensitive condition shaped by cumulative physiological changes across the life course. This review summarises current evidence relating vascular ageing, hormonal regulation, metabolic dysfunction, and reproductive history to blood pressure regulation in women. Materials and Methods: A narrative review of the literature was conducted using PubMed, Scopus and Google Scholar. Clinical, epidemiological, and mechanistic studies were synthesised to evaluate factors influencing hypertension in women. Reports in which menopausal status was not defined, or previous reproductive milestones were not documented, were excluded or interpreted with caution. Results: Evidence suggests that menopause, vascular ageing, metabolic dysfunction, androgen to oestrogen balance, and reproductive history interact to influence endothelial function, neurohormonal regulation, renal sodium handling, and vascular resistance. Ageing-related mechanisms, including cellular senescence, chronic low-grade inflammation, and genetic susceptibility, may contribute to increased cardiovascular risk. Hypertensive disorders of pregnancy identify women who are at higher risk of developing cardiovascular disease later in life and provide an opportunity for earlier risk assessment and prevention. Emerging therapies, including GLP-1 receptor agonists and SGLT2 inhibitors, may offer additional options for improving cardiovascular risk management, although their role in sex-specific prevention remains an evolving area of research. Conclusions: Hypertension in women is best understood within a life-course framework. Incorporating reproductive history, menopausal status, metabolic health, and emerging risk markers may improve cardiovascular risk assessment and support earlier intervention. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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21 pages, 2885 KB  
Article
Microfluidic Fibroblast Cell Culture Chip for Embryo Co-Culture: Analysis of Preimplantation Embryo Viability and Development Potential
by Ya-Shun Lo, Tian-Chi Tsai, Te-Yu Tsou, Kai-Cheng Chang, Yi-Wen Wang, Wen-Syang Hsu, Da-Jeng Yao and Hong-Yuan Huang
Int. J. Mol. Sci. 2026, 27(15), 6592; https://doi.org/10.3390/ijms27156592 - 24 Jul 2026
Viewed by 153
Abstract
Preimplantation embryo development requires a tightly regulated microenvironment that is not fully reproduced by conventional static culture. We developed a polydimethylsiloxane-based microfluidic embryo co-culture platform integrating compartmentalized architecture with dynamic perfusion to simulate physiological conditions. The study included two stages. First, NIH/3T3 mouse [...] Read more.
Preimplantation embryo development requires a tightly regulated microenvironment that is not fully reproduced by conventional static culture. We developed a polydimethylsiloxane-based microfluidic embryo co-culture platform integrating compartmentalized architecture with dynamic perfusion to simulate physiological conditions. The study included two stages. First, NIH/3T3 mouse fibroblasts were evaluated as helper cells under three culture conditions after transition to embryo culture medium. Helper-cell viability in the dynamic chip was 84.72%, compared with 71.91% after manual medium replacement in 24-well plates and 94.27% in the 24-well control group. Second, mouse embryos were cultured under four conditions: conventional 24-well plates, static microfluidic chip culture with co-culture, dynamic microfluidic chips without co-culture, and dynamic microfluidic chip co-culture. Blastocyst formation rates were 100.0% (9/9), 0.0% (0/6), 33.3% (3/9), and 55.5% (5/9), respectively. Because no inferential statistical analysis was performed, these proportions are interpreted descriptively. Nevertheless, the blastocyst formation in the microfluidic co-culture group supports the technical feasibility of integrating dynamic perfusion and helper-cell co-culture within a single platform. Further optimization and validation are required. This platform provides a foundation for future development of advanced embryo culture technologies including patient-specific endometrial co-culture systems in assisted reproduction, disease modeling, or drug development. Full article
(This article belongs to the Collection Latest Review Papers in Molecular Biophysics)
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23 pages, 3276 KB  
Review
The Molecular and Cellular Mechanisms of Melatonin: From Physiological Actions to Clinical Applications in Reproductive Medicine
by Kelly I-Rong Lee, Jie-Hong Chen and Kuo-Hu Chen
Int. J. Mol. Sci. 2026, 27(14), 6524; https://doi.org/10.3390/ijms27146524 - 22 Jul 2026
Viewed by 238
Abstract
Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive [...] Read more.
Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive medicine. Available evidence suggests that melatonin may influence mitochondrial quality control (MQC) through multiple interconnected processes, including ROS regulation, mitochondrial dynamics, mitophagy, biogenesis, and mitochondrial inflammatory signaling. In mitochondria, melatonin can attenuate electron transport chain-derived oxidative stress through direct radical-scavenging reactions, antioxidant metabolite formation, and indirect activation of endogenous antioxidant systems. Experimental studies further suggest that melatonin may modulate Drp1-mediated fission, OPA1- and Mfn1/2-associated fusion, PINK1/Parkin-mediated mitophagy, and SIRT1/PGC-1α-related mitochondrial biogenesis. In reproductive medicine, melatonin has been investigated as a potential adjunctive strategy in assisted reproductive technology, endometriosis, and polycystic ovary syndrome. However, clinical evidence remains heterogeneous, and most human studies have evaluated reproductive or biochemical outcomes rather than direct MQC-related biomarkers. Therefore, although melatonin represents a promising mitochondria-targeted adjunct, standardized dosing strategies, tissue-level pharmacodynamic assessment, and validated mitochondrial biomarkers are needed to determine whether these mechanisms translate into reproducible clinical benefit. Full article
(This article belongs to the Special Issue Advances in Melatonin Biology and Signaling)
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24 pages, 1884 KB  
Article
Determining Critical Physiological and Drug Specific Parameters for Enhancing a Physiologically Based Pharmacokinetics Model for the Female Reproductive Tract
by An Le, Riyazuddin Mohammed, Junmei Zhang, Lin Wang, Guru R. Valicherla, Phillip W. Graebing, Robert Bies and Lisa C. Rohan
Pharmaceutics 2026, 18(7), 903; https://doi.org/10.3390/pharmaceutics18070903 - 22 Jul 2026
Viewed by 269
Abstract
Background/Objectives: Given the potential for achieving high concentrations at the target site while limiting systemic exposure, delivering drugs directly to the female reproductive tract (FRT) is emerging as a promising strategy for enhancing women’s reproductive health. However, quantitative data describing matrix-specific solubility, [...] Read more.
Background/Objectives: Given the potential for achieving high concentrations at the target site while limiting systemic exposure, delivering drugs directly to the female reproductive tract (FRT) is emerging as a promising strategy for enhancing women’s reproductive health. However, quantitative data describing matrix-specific solubility, matrix-specific binding, and permeability across FRT tissues remain limited, constraining development of physiologically based pharmacokinetic (PBPK) models for intravaginal and intrauterine therapies. Methods: Our work was conducted to help fill this critical gap, evaluating four model drugs with diverse physicochemical and transporter profiles, dapivirine (DPV), levonorgestrel (LNG), MK-2048, and 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA; also known as islatravir or MK-8591) in in vitro and ex vivo human models. Plasma solubility, matrix-specific binding in plasma, cervicovaginal fluid, and FRT tissues, and bidirectional permeability across FRT tissues were quantified. Results: Our results demonstrated that the plasma solubility varied markedly across compounds, following lipophilicity trends, with DPV (34.14 ± 1.04 µg/mL) and EFdA (1808.02 ± 67.36 µg/mL) exhibiting the lowest and highest solubility, respectively. Hydrophobicity-dependent solubility enhancement by plasma proteins (~2× to >30× higher comparing to aqueous solubility in the literature) was observed for all four model drugs. Apparent binding in plasma, cervicovaginal fluid, and FRT tissues was highly correlated with the model compounds’ lipophilicity, with DPV having the most highly matrix-specific binding (97–99%) and EFdA having the least matrix-specific binding with the greatest variability (15–62%). Regional permeability differed significantly across FRT tissues: the human ectocervix, myometrium, endometrium, and fallopian tubes demonstrated distinct transport patterns consistent with epithelial architecture and the transporter-substrate status of the model compounds. Efflux transporter involvement was evident for MK-2048 and EFdA in Caco-2 models (efflux ratios 2.59 and 7.14, respectively), but was less pronounced in the 3D vaginal model and ex vivo tissues. Across all datasets, permeability and binding were strongly influenced by drug lipophilicity and ionization characteristics. Conclusions: Collectively, these findings demonstrate the interplay among solubility, matrix-specific binding, and tissue permeability in governing local drug distribution within the FRT. The experimentally derived parameters provide quantitative inputs for FRT PBPK model development, and are expected to inform design of safe and effective localized therapies for women’s reproductive health. Full article
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27 pages, 4805 KB  
Review
Optimizing Reduced Protein Diets for an Efficient and Sustainable Layer Production
by Aamir Nawab, Thi Hiep Dao, Eunjoo Kim, Tamsyn M. Crowley and Amy F. Moss
Agriculture 2026, 16(14), 1563; https://doi.org/10.3390/agriculture16141563 - 21 Jul 2026
Viewed by 474
Abstract
Dietary protein is essential for poultry performance, influencing egg production, growth, immunity, and physiological functions. However, the high cost and environmental impact of soybean meal has encouraged the development of reduced crude protein (CP) diets supplemented with crystalline amino acids (AAs), coupled with [...] Read more.
Dietary protein is essential for poultry performance, influencing egg production, growth, immunity, and physiological functions. However, the high cost and environmental impact of soybean meal has encouraged the development of reduced crude protein (CP) diets supplemented with crystalline amino acids (AAs), coupled with the reduced cost and improved availability of synthetic AA. This strategy enables precise AA balancing, improves nitrogen utilization, and reduces nitrogen excretion and ammonia emissions. Among these strategies, supplementation with arginine (Arg), an indispensable AA in chickens, is particularly important due to its critical roles in protein synthesis, reproductive function, and eggshell formation. In addition, functional Arg precursors, such as guanidinoacetic acid (GAA) and citrulline (Cit), can further enhance Arg availability while supporting energy metabolism and hormonal regulation. Despite these benefits, excessive protein reduction without adequate AA balance can impair laying performance, particularly in aged hens. Furthermore, nutrient digestibility remains a key limitation in reduced protein (RP) diets, as non-starch polysaccharides present in cereal-based feeds can reduce nutrient availability. The inclusion of exogenous enzymes, such as xylanase and β-glucanase, can improve digestibility, while phytase supplementation further enhances nutrient utilization by increasing phosphorus availability and mitigating the anti-nutritional effects of phytate; however, responses are often inconsistent. Another critical factor is maintaining an optimal energy-to-protein ratio, as imbalances may lead to increased fat deposition and reduced productive performance. While supplementation of key limiting AAs (lysine, methionine, and threonine) supports protein reduction, other AAs, such as Arg, isoleucine, and valine, may become limiting in RP diets. Hence, this review explores developments toward RP diets by highlighting three key strategies: enzyme supplementation to enhance nutrient digestibility, inclusion of functional Arg sources to improve performance and bone quality, and optimization of the energy–protein ratio in RP diets through precise AA formulation, with the overall aim to improve the sustainability of the poultry industry. Full article
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20 pages, 1415 KB  
Article
Effect of Sodium Selenite and Hydroxy-Selenomethionine Supplementation in Hanwoo Cows on Reproductive Performance and Growth Performance of Their Offspring
by Young-Lae Kim, So-Hee Lee, Jeong-Keum Park, Gi-Hwal Son, Chang-Sik Choi, Chang-Woo Lee, Ju-Gyo Jeong, Jun Cui, Yun-He Zheng, Ji-Woo Choi, Young-Hwan We, Jong-Kook Bahn, Hyo-Won Seo, Jong-Suh Shin, Byung Ki Park and Min Ji Kim
Animals 2026, 16(14), 2258; https://doi.org/10.3390/ani16142258 - 21 Jul 2026
Viewed by 201
Abstract
Selenium is an essential trace mineral that is involved in several biological processes, including antioxidant defense, immune function, and reproductive efficiency. Therefore, this study aimed to investigate the effects of selenium supplementation in Hanwoo cows on maternal reproductive performance and physiological responses, as [...] Read more.
Selenium is an essential trace mineral that is involved in several biological processes, including antioxidant defense, immune function, and reproductive efficiency. Therefore, this study aimed to investigate the effects of selenium supplementation in Hanwoo cows on maternal reproductive performance and physiological responses, as well as the early growth and metabolic profiles of the offspring. Hanwoo cows (n = 30) were assigned to control (no supplement), sodium selenite (SS; 0.3 ppm/head/day), and hydroxy-selenomethionine (OH-SeMet; 0.3 ppm/head/day) treatment groups. Maternal reproductive performance and calf growth were examined. Cows in the OH-SeMet group had a significantly shorter postpartum interval and 4.25-fold higher conception rates than those in the control and SS groups. Plasma selenium concentrations were significantly higher in the OH-SeMet group at 3 months postpartum, with improved antioxidant status. Calves from OH-SeMet-supplemented cows had greater birth weights and higher plasma selenium, total immunoglobulin, and ghrelin concentrations. In addition, ruminal microbiota analysis revealed an increased Firmicutes-to-Bacteroidetes ratio in cows supplemented with OH-SeMet. In conclusion, dietary organic selenium supplementation in Hanwoo cows improved maternal reproductive efficiency and antioxidant status and promoted early growth in their offspring. Full article
(This article belongs to the Section Animal Nutrition)
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21 pages, 2985 KB  
Article
Body Mass Index and Ovarian Follicular Response in Assisted Reproductive Technology: A Cross-Sectional Analysis
by Michelle Estefanía Canchig-Aguilar, Washington David Guevara-Castillo, José Isaac Zablah, José Augusto Durán-Chávez, Nelly Andrade Mejía, Lupe Carolina Espinoza, Lilian Sosa and Raynier Zambrano-Villacres
Reprod. Med. 2026, 7(3), 35; https://doi.org/10.3390/reprodmed7030035 - 21 Jul 2026
Viewed by 305
Abstract
Background: Excess adiposity has been associated with endocrine and metabolic alterations that may affect ovarian physiology and outcomes in assisted reproductive technology (ART). Objectives: The purpose of this study was to evaluate whether body mass index (BMI) was independently associated with [...] Read more.
Background: Excess adiposity has been associated with endocrine and metabolic alterations that may affect ovarian physiology and outcomes in assisted reproductive technology (ART). Objectives: The purpose of this study was to evaluate whether body mass index (BMI) was independently associated with ovarian follicular response in women undergoing assisted reproductive procedures. Methods: A cross-sectional study was conducted including 259 women aged 18 to 43 years. Analyses included nutritional status, diet quality, and follicular response. Associations were analyzed using chi-square and Kruskal–Wallis tests and negative binomial regression adjusted for age and indication. Results: Mean age was 32.8 ± 6.3 years, and mean BMI was 24.7 ± 3.2 kg/m2. Diet quality was not associated with follicle number or morphological quality. Overall, 47.5% of participants had normal weight, 42.9% were overweight, and 6.9% had class I obesity. Follicular yield differed across BMI categories in unadjusted analyses (p = 0.017), but BMI was not independently associated with follicle count after adjustment (IRR = 1.010; 95% CI: 0.983–1.036; p = 0.488). Age remained the only independent predictor, with each additional year associated with a 5.9% reduction in expected follicle count (IRR = 0.941; 95% CI: 0.920–0.963; p < 0.001). Conclusions: BMI was not independently associated with follicular yield after adjustment, whereas age remained the principal determinant of ovarian response. These findings should be confirmed in prospective studies incorporating ovarian reserve markers and stimulation-related variables. Full article
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Review
Fumonisin-Induced Disruptions in Sphingolipid Metabolism: Implications for Steroid Hormone Biosynthesis and Hormone Modulation
by Edward Agyarko, Omeralfaroug Ali, Lucy Ikanya, Attila Zsarnovszky, Melinda Kovács and András Szabó
Toxins 2026, 18(7), 316; https://doi.org/10.3390/toxins18070316 - 21 Jul 2026
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Abstract
Fumonisins, a class of mycotoxins produced primarily by Fusarium fungi, pose significant health risks to humans and animals through contamination of the food and feed chains. They rank among the most prevalent mycotoxins contaminating maize and maize-derived feeds worldwide, resulting in chronic dietary [...] Read more.
Fumonisins, a class of mycotoxins produced primarily by Fusarium fungi, pose significant health risks to humans and animals through contamination of the food and feed chains. They rank among the most prevalent mycotoxins contaminating maize and maize-derived feeds worldwide, resulting in chronic dietary exposure of both humans and livestock populations across many regions. Their core mechanism of action is the inhibition of ceramide synthases (CerS), which disrupts the essential balance of sphingolipid metabolism by causing an accumulation of free sphingoid bases and a depletion of complex sphingolipids. Both sphingolipids and steroidogenesis are metabolically linked to mitochondrial, membrane and kinase-cascade mechanisms; hence this metabolic disruption may consequently affect steroid hormone biosynthesis, triggering toxicity phenotypes marked by impaired gametogenesis hormonal imbalances, and compromised pregnancy outcomes across mammalian species. Despite the established link between fumonisins and sphingolipid disruption, there is a gap in the literature, as no study to date has integrated sphingolipid disruptions with steroid hormone levels in a dose-dependent manner within reproductive tissues in vivo. This review synthesizes current scientific knowledge across mammalian species to highlight the risks fumonisins pose to reproductive physiology and to identify directions for future research. Full article
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