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15 pages, 480 KB  
Review
Efficacy and Safety of Semaglutide in Patients with Polycystic Ovary Syndrome: A Scoping Review
by Sandro La Vignera and Rosita A. Condorelli
Biomedicines 2026, 14(8), 1845; https://doi.org/10.3390/biomedicines14081845 - 17 Aug 2026
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, characterised by hyperandrogenism, ovulatory dysfunction, and metabolic disturbances. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has emerged as a promising therapeutic option for weight management and [...] Read more.
Background/Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, characterised by hyperandrogenism, ovulatory dysfunction, and metabolic disturbances. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has emerged as a promising therapeutic option for weight management and metabolic optimisation in PCOS. This scoping review evaluates the efficacy and safety of semaglutide in women with PCOS, with pre-specified primary outcomes (weight loss, metabolic parameters) and secondary outcomes (menstrual cyclicity, hormonal regulation, ovarian function, safety). Methods: A systematic literature search was conducted across four electronic databases (SciSpace Deep Search, SciSpace Full Text, Google Scholar, and PubMed) from inception through July 2026. Studies were included if they evaluated semaglutide in women with confirmed PCOS and reported outcomes related to weight loss, hormonal regulation, metabolic parameters, ovarian function, or safety. Two independent reviewers screened 356 unique records; 28 reports were assessed for eligibility, of which full-text access was confirmed for 5, and the remaining 23 were assessed using published abstracts or conference summaries. Two additional records were subsequently excluded due to unverifiable source identification, yielding a final corpus of 25 studies. The review adhered to the PRISMA-ScR reporting guidelines. Results: Twenty-five studies met the inclusion criteria. Semaglutide produced clinically relevant weight reduction (mean 7.6–11.5 kg over 3–6 months; ≥5% weight loss in approximately 80% of patients in responsive cohorts) with concurrent improvements in fasting insulin and HOMA-IR, based predominantly on observational and small-sample study designs. Improvements in menstrual regularity were reported by several studies; however, these data derive largely from conference abstracts or small pilot studies and should be interpreted cautiously. Gastrointestinal adverse events were the most frequent side effects, generally mild-to-moderate and transient. Important safety considerations include gallbladder disease, pancreatitis, and the risk of inadvertent pregnancy exposure following the potential restoration of ovulatory function; semaglutide must be discontinued before planned conception. Conclusions: Based on preliminary evidence from heterogeneous and predominantly low-quality studies, semaglutide shows potentially beneficial effects on weight, metabolic health, and menstrual regularity in women with PCOS. Confirmatory data on ovulation rates, reproductive outcomes, and long-term safety from large-scale RCTs with standardised endpoints are needed before definitive clinical recommendations can be made. Full article
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34 pages, 14993 KB  
Article
A Unified Multi-Task Vision Transformer for Interpretable Ovarian Tumour Analysis
by Abdussamad Abdullahi Musa, David Emmanuel, Adeeb Alchaikh Hassan and Anil Fernando
Electronics 2026, 15(16), 3662; https://doi.org/10.3390/electronics15163662 - 17 Aug 2026
Abstract
Ovarian cancer remains a leading cause of gynaecological cancer mortality, and ultrasound-based deep learning systems for its diagnosis are typically built as separate post hoc processes for classification, segmentation, and interpretability, which introduces workflow inefficiencies and may produce inconsistent predictions. This work addresses [...] Read more.
Ovarian cancer remains a leading cause of gynaecological cancer mortality, and ultrasound-based deep learning systems for its diagnosis are typically built as separate post hoc processes for classification, segmentation, and interpretability, which introduces workflow inefficiencies and may produce inconsistent predictions. This work addresses that limitation. We propose UM-TOTA (Unified Multi-Task Ovarian Tumour Architecture), a Vision Transformer (ViT)-based architecture that performs eight-class tumour classification, three-class malignancy detection, tumour segmentation, and clinical concept interpretability within a single unified framework. We integrate a concept bottleneck guided by the IOTA and O-RADS clinical guidelines to enable transparent decision-making through medical concepts that clinicians can understand, and we employ combined adaptive t-vMF Dice and boundary-enhanced segmentation losses with progressive task weighting to stabilise multi-task optimisation. We evaluated the model on the Multi-Modality Ovarian Tumor Ultrasound (MMOTU) 2D dataset under two protocols: image-level 5-fold stratified cross-validation, and the patient-disjoint partition released with the dataset. Under cross-validation, UM-TOTA achieved 80.26% ± 1.10% accuracy (97.06% one-vs-rest macro specificity) for eight-class classification, 90.88% ± 1.14% accuracy (90.41% specificity) for malignancy detection, and 77.29% ± 1.29% Dice for segmentation. Under the patient-disjoint partition, which excludes any overlap of patients between training and testing, the corresponding values were 78.46%, 89.13%, and 75.41%, a reduction of under 2.2 percentage points on every metric. The UM-TOTA reduced the computational parameter load by approximately 65.1% relative to sequential single-task pipelines. The learned concepts aligned with established malignancy criteria, identifying vascularisation, solid components, and papillary projections as key predictors. This unified approach offers an efficient and interpretable framework for clinical ovarian ultrasound workflows. Full article
(This article belongs to the Special Issue Artificial Intelligence in Graphics and Images)
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36 pages, 5176 KB  
Review
Metabolic and Anti-Inflammatory Effects of Berberine—Rationale for Its Therapeutic Potential in Polycystic Ovary Syndrome
by Dariusz Szukiewicz
Int. J. Mol. Sci. 2026, 27(16), 7287; https://doi.org/10.3390/ijms27167287 - 15 Aug 2026
Viewed by 239
Abstract
Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age and is characterized by ovarian hyperandrogenism and irregular ovulation. This often leads to infertility. Beyond reproduction, PCOS causes widespread metabolic issues such as insulin resistance (IR), increasing long-term risks [...] Read more.
Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age and is characterized by ovarian hyperandrogenism and irregular ovulation. This often leads to infertility. Beyond reproduction, PCOS causes widespread metabolic issues such as insulin resistance (IR), increasing long-term risks for diabetes, obesity, and heart disease. In a vicious cycle, IR acts as a core driver of both clinical symptoms and associated obesity, whereas compensatory hyperinsulinemia stimulates ovarian androgen production, causing ovulatory dysfunction and worsening weight gain, with immune imbalances exacerbating systemic chronic low-grade inflammation (CLGI). Berberine is a natural plant alkaloid that, owing to its multifaceted metabolic effects—including activation of 5′ adenosine monophosphate (AMP)-activated protein kinase (AMPK) and improvement of insulin sensitivity—effectively supports the restoration of homeostasis in women with PCOS. The aim of this narrative review is to comprehensively analyze the metabolic and anti-inflammatory actions of berberine, which, in combination with the known pathomechanisms of PCOS, may constitute a rationale for its therapeutic application. Attention was given to the necessity of actions aimed at increasing the bioavailability of berberine and to the consequences of the fact that berberine, unlike metformin, which is commonly used and has similar properties, is a dietary supplement and not a Food and Drug Administration (FDA)-approved prescription drug. Full article
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18 pages, 14007 KB  
Article
Gametocyte-Specific Factor 1 Is Essential for Male Fertility and Transposon Homeostasis in Plutella xylostella
by Jianying Liao, Muhammad Asad, Yanpeng Chang, Beihua Qin, Chengbin Liu, Xiping Du, Jinzhi Chen and Guang Yang
Insects 2026, 17(8), 846; https://doi.org/10.3390/insects17080846 - 14 Aug 2026
Viewed by 90
Abstract
Gametocyte-specific factor 1 (Gtsf1) plays a pivotal role in the gonadal development by transposon silencing via the piRNA pathway in Drosophila melanogaster and Bombyx mori, and is implicated in the female sex determination in B. mori. However, its function remains elusive [...] Read more.
Gametocyte-specific factor 1 (Gtsf1) plays a pivotal role in the gonadal development by transposon silencing via the piRNA pathway in Drosophila melanogaster and Bombyx mori, and is implicated in the female sex determination in B. mori. However, its function remains elusive in other insect species, including Plutella xylostella, a highly destructive pest in cruciferous crops. In this study, we characterized PxGtsf1, encoding a 27.84 kDa protein containing two conserved U11-48K-like CHHC zinc-finger domains. PxGtsf1 was predominantly expressed in male pupae, males and testes. Using CRISPR/Cas9 technique, we successfully generated a homozygous PxGtsf1-knockout strain (△PxGtsf1) with 11 bp deletion. △PxGtsf1 females exhibited normal morphology in terms of external genitalia, body weight, ovariole morphology, ovariole length, oocytes number, and internal ovarian structure, and maintained the expression levels of genes related to female sex determination and fertility. In contrast, △PxGtsf1 males displayed reduced testis size and enlarged eupyrene sperm bundles, whereas apyrene sperm bundles appeared normal. Wild-type (WT) or △PxGtsf1 females mated with △PxGtsf1 males had significantly smaller bursa copulatrix distention area compared to those mated with WT males. Furthermore, WT or △PxGtsf1 females mated with △PxGtsf1 males produced significantly fewer eggs with lower hatching rates than those mated with WT males. Co-immunoprecipitation assays revealed that PxGtsf1 specifically interacts with PxPiwi. Small RNA sequencing further showed that PxGtsf1 knockout resulted in transposon dysregulation in the testes without affecting overall piRNA abundance, suggesting that PxGtsf1 functions in piRNA-mediated transposon regulation rather than global piRNA biogenesis. PxGtsf1 is first reported to be specifically required for male fertility in Lepidoptera insects but is dispensable for female sex determination., PxGtsf1 regulates transposon homeostasis without affecting global piRNA biogenesis. These findings provide new insights into the diverse functions of Gtsf1 in Lepidopteran insects. Full article
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18 pages, 17431 KB  
Article
Maternal Excessive Lard Versus Palm Oil Intake in Mice Drives Sex-Specific Reproductive Dysfunction in Offspring
by Yan Xu, Yue Zhang, Kaile Guan, Qi Chen, Chenchen Geng, Lingfeng Dan, Jiaxin Zhao, Yansong Zhang and Huimin Lu
Nutrients 2026, 18(16), 2631; https://doi.org/10.3390/nu18162631 - 12 Aug 2026
Viewed by 247
Abstract
Objectives: This study clarified sex-specific short- and long-term impacts of maternal excessive palm oil (plant-derived saturated) and lard (animal-derived saturated fat) intake on offspring reproductive health and underlying mechanisms. Methods: Female mice were randomized to control, palm oil, or lard diets [...] Read more.
Objectives: This study clarified sex-specific short- and long-term impacts of maternal excessive palm oil (plant-derived saturated) and lard (animal-derived saturated fat) intake on offspring reproductive health and underlying mechanisms. Methods: Female mice were randomized to control, palm oil, or lard diets during gestation and lactation. Offspring received a control diet post-weaning until adulthood, followed by an optional 16-week HFD rechallenge. Gonadal weight and organ index, sperm quality, ovarian follicle number, serum sex hormones, metabolic phenotypes (serum lipid profiles, glucose and insulin tolerance), oxidative stress, apoptosis, proliferation, and transcriptomic profiles were detected at weaning, early and late adulthood. Results: In males, excessive maternal lard intake significantly induces sperm malformation and reduces seminiferous tubule diameter and spermatogenic epithelium thickness upon HFD rechallenge during adulthood, with no changes in oxidative stress, proliferation, and apoptosis. Transcriptomics identified Slc24a5 upregulation as a potential correlate through metal ion transmembrane transporter activity and cellular calcium ion homeostasis. Under normal adult diets, reduced sperm motility resulting from maternal excess lard may be mediated by apoptosis, whereas that induced by maternal high palm oil likely arises from suppressed proliferation and thinner spermatogenic epithelium. GO analysis revealed palm oil-specific Ugt1a5 upregulation associated with altered steroid hormone metabolism. In females, maternal palm oil intake reduced primordial follicles and increased atresia, with sequencing predicted to involve Nedd4 downregulation; lard intake elevated ovarian oxidative stress and atresia only upon HFD rechallenge, with Lamc3 upregulation predicted as a putative regulatory factor. Conclusions: Maternal excessive intake of saturated fat exerts offspring reproductive damage in a sex-specific and source-dependent manner with distinct mechanisms. This work provides novel insights into fat source-dependent and sex-specific effects of nutritional interventions during pregnancy and lactation. Full article
(This article belongs to the Section Lipids)
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21 pages, 7740 KB  
Article
Reproductive and Cardiometabolic Characterization of a Letrozole- and High-Fat Diet-Induced PMOS-like Rat Model: An Experimental Study
by Milica Milinkovic Sorgic, Aleksandar Matic, Vladimir Jakovljevic, Nikola Jovic, Sladjana Novakovic, Teodora Todorovic, Jovan Milosavljevic, Bozidar Pindovic, Jasmina Sretenovic, Petar Canovic, Jovana Jakovljevic Uzelac and Jovana Joksimovic Jovic
Pathophysiology 2026, 33(3), 61; https://doi.org/10.3390/pathophysiology33030061 - 11 Aug 2026
Viewed by 129
Abstract
Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of [...] Read more.
Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies. Full article
(This article belongs to the Section Metabolic Disorders)
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22 pages, 10105 KB  
Article
Cepharanthine Reduces Endometriosis Lesions and Alters Mitochondrial and Autophagy-Related Signals in Endometriotic Stromal Cells
by Miji Kim, Wonhyoung Park, Hee Seung Kim, Whasun Lim, Gwonhwa Song and Sunwoo Park
Molecules 2026, 31(15), 2722; https://doi.org/10.3390/molecules31152722 - 5 Aug 2026
Viewed by 330
Abstract
Endometriosis is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue, leading to pelvic pain and infertility. Although cepharanthine has well-established anti-inflammatory properties, its therapeutic potential and underlying mechanisms in endometriosis remain largely unexplored. In this study, the effects of [...] Read more.
Endometriosis is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue, leading to pelvic pain and infertility. Although cepharanthine has well-established anti-inflammatory properties, its therapeutic potential and underlying mechanisms in endometriosis remain largely unexplored. In this study, the effects of cepharanthine were evaluated using a surgically induced mouse model and immortalized human endometrial stromal cell models. Cepharanthine treatment significantly reduced the calculated lesion volume, whereas wet lesion weight did not differ significantly between the groups. Cepharanthine was also accompanied by reduced spleen weight and alterations in the CD4+ helper T-cell population in vivo. In immortalized human ovarian endometriotic stromal cells (ihOESCs), cepharanthine significantly decreased cell viability, induced apoptosis, and disrupted cell-cycle progression. Cepharanthine altered autophagy-related signaling, accompanied by increased acidic vesicle-associated signals and accumulation of LC3B-II and p62/SQSTM1; however, the direction of autophagic flux remains unclear. These changes were associated with elevated reactive oxygen species production, intracellular Ca2+ redistribution, and mitochondrial dysfunction. Collectively, these findings indicate that cepharanthine reduces calculated lesion volume in vivo and alters mitochondrial function, autophagy-related signaling, apoptosis and cell-cycle progression in ihOESCs, supporting its potential as a therapeutic candidate. Full article
(This article belongs to the Section Natural Products Chemistry)
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57 pages, 15502 KB  
Review
Therapeutic Potential of Anti-Obesity Drugs in Obesity-Associated Female Reproductive Dysfunction: Translating Mechanistic Evidence into Personalized Clinical Strategies
by Fani-Niki Varra, Panagiotis Theodosis-Nobelos, Viktoria-Konstantina Varra and Michail Varras
Medicina 2026, 62(8), 1445; https://doi.org/10.3390/medicina62081445 - 25 Jul 2026
Viewed by 314
Abstract
Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic–pituitary–gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy [...] Read more.
Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic–pituitary–gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine/topiramate, bupropion/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
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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 514
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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17 pages, 2799 KB  
Article
TGF-β Is Critical for Ovarian Cancer Migration, Invasion, and Chemosensitivity
by Christopher Elms, Wei Wei and Michael J. Birrer
Cancers 2026, 18(14), 2268; https://doi.org/10.3390/cancers18142268 - 15 Jul 2026
Viewed by 649
Abstract
Background/Objectives: Standard treatment for ovarian cancer includes surgery and chemotherapy, either as primary “debulking” surgery followed by adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval debulking surgery. The degree of surgical resection correlates with overall survival, with “suboptimal debulking” (visible remaining cancer) being [...] Read more.
Background/Objectives: Standard treatment for ovarian cancer includes surgery and chemotherapy, either as primary “debulking” surgery followed by adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval debulking surgery. The degree of surgical resection correlates with overall survival, with “suboptimal debulking” (visible remaining cancer) being a poor prognostic variable. TGF-β pathway activation is associated with ovarian cancers that cannot be optimally debulked. To test the role of this pathway in ovarian cancer biology, modulation of the pathway was performed in in vitro and in vivo ovarian cancer model systems. Methods: A small molecule TGF-β receptor 1 (TGFBR1) kinase inhibitor, LY2157299, was used to test the in vitro cellular adhesion, proliferation, migration and invasive ability of ovarian cancer cells in culture. A TGF-β responsive reporter construct was used to determine the role of TGF-β pathway in those interactions. To test the effects of TGF-β inhibition in vivo, TGFBR1 and TGFBR2 CRISPR knockout cells were generated and examined for growth and sensitivity to chemotherapy. Results: For ovarian cancer cells responsive to exogenous TGF-β1 treatment, LY2157299-mediated the TGF-β pathway inhibition decreased cell migration and invasion, as well as mesothelial cell to cancer cell adhesion, proliferation, and migration. TGFBR1 and TGFBR2 CRISPR knockout cells showed decreased proliferation baseline or when treated with TGF-β and LY2157299. TGFBR2 CRISPR cells also showed increased sensitivity to cisplatin, with a significant decrease in tumor weight in vivo. Conclusions: TGF-β pathway inhibition successfully targeted many of the cancer cell behaviors that could contribute to suboptimally debulked patients and showed an additive anti-tumor effect in conjunction with cisplatin. LY2157299 treatment is clinically limited due to solubility, but other TGF-β inhibitors could be highly efficacious treatment options. Full article
(This article belongs to the Section Molecular Cancer Biology)
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22 pages, 6638 KB  
Article
Integrated Application of Iso-Seq and RNA-Seq Analyses to Uncover Genes Involved in Ovarian Development in Platypharodon extremus
by Zhuoyu Yang, Yanping Zhang, Wei Ka, Wenjing He, Yujie Yang, Wenlong Jiao and Jianlin Wang
Fishes 2026, 11(7), 411; https://doi.org/10.3390/fishes11070411 - 12 Jul 2026
Viewed by 371
Abstract
This study focused on Platypharodon extremus, a species endemic to the Qinghai–Tibet Plateau, and systematically analyzed its reproductive biology, sex steroid hormones, ovarian histology, and transcriptomic characteristics throughout its complete reproductive cycle (August 2020 to June 2021). The results demonstrated that the [...] Read more.
This study focused on Platypharodon extremus, a species endemic to the Qinghai–Tibet Plateau, and systematically analyzed its reproductive biology, sex steroid hormones, ovarian histology, and transcriptomic characteristics throughout its complete reproductive cycle (August 2020 to June 2021). The results demonstrated that the body length, height, body weight, and gonadal weight of female individuals continuously increased with age, while the Gonadosomatic index (GSI) was lowest during the breeding season (June–August) and gradually rose during the non-breeding period. Serum estradiol (E2) and progesterone (P4) exhibited rhythmic fluctuations corresponding to ovarian development: E2 rose from 25.77 ng/L in stage-I to 146.00 ng/L in stage-V, then declined post-ovulation; P4 increased from 59.88 pmol/L in stage-I to 239.03 pmol/L in stage-V, showing a significant decrease after ovulation. Histological observations classified ovarian development into stages I–VI, clearly delineating the complete process from oogonium proliferation, cortical vesicle formation, yolk accumulation, maturation to postpartum regression. To explore molecular changes during the transition from vitellogenesis to oocyte maturation, we built a reference transcriptome with 30,060 non-redundant transcripts (average length = 1975 bp) using PacBio and Illumina data, and 91.87% of these transcripts received functional annotation hits against public databases. A comparative differential expression analysis was performed between ovarian stage III (active yolk accumulation) and stage V (oocyte fully matured). A total of 11,324 differentially expressed genes were identified (5249 upregulated and 6175 downregulated) between these two stages. GO enrichment analysis revealed predominant involvement in cellular processes, cellular components, and catalytic activities, while KEGG analysis demonstrated significant enrichment in metabolic pathways, PI3K-Akt, MAPK, and calcium signaling pathways. Quantitative PCR (qPCR) validation confirmed that candidate genes, including pik3a, calm, mapk1 map2k ddx49, and igf2 were significantly upregulated at stage V. These differentially expressed genes (DEGs) may represent potential molecular signatures linked to the transition from vitellogenesis to oocyte maturation. Our integrated transcriptomic and qPCR data identify potential gene candidates involved in ovarian maturation; however, these findings reveal correlation rather than direct regulatory causality. This study offers fundamental data and theoretical insights for understanding the reproductive regulatory mechanisms and aquaculture management of this endemic species. Full article
(This article belongs to the Special Issue Physiological and Behavioral Studies in Aquaculture)
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22 pages, 6080 KB  
Article
DNAH6: A Newly Identified Gene Improving Total Number Born with Functional Enrichment Analysis in French Large White Pigs
by Lin Zhang, Junjie Shao, Chenchen Yang, Xiangdong Ding, Chenkai Liu, Chunmei Han and Weiping Ao
Animals 2026, 16(14), 2158; https://doi.org/10.3390/ani16142158 - 11 Jul 2026
Viewed by 333
Abstract
Reproductive characteristics in pigs exhibit low heritability levels. Performing genome-wide association studies (GWAS) to pinpoint candidate genes for these characteristics is crucial for enhancing swine fertility. In this research, hair samples were gathered from 689 French Large White sows within the primary breeding [...] Read more.
Reproductive characteristics in pigs exhibit low heritability levels. Performing genome-wide association studies (GWAS) to pinpoint candidate genes for these characteristics is crucial for enhancing swine fertility. In this research, hair samples were gathered from 689 French Large White sows within the primary breeding population for DNA extraction purposes. Genotyping was carried out using a 50K liquid-phase SNP chip. Four statistical approaches—MLM, CMLM, FarmCPU, and BLINK—were utilized to perform GWAS on nine reproductive characteristics: total number born (TNB), litter birth weight (LBW), number born alive (NBA), number of healthy births (NHB), number of weak piglets (NWP), number of stillbirths (NSB), number of mummies (MUM), number of deformed fetuses (NDF), and adjusted 21-day litter weight (ALW). siRNAs targeting significantly associated genes were designed, and viral transfection was employed to introduce them into the ovarian granulosa cells of Large White sows to explore gene functions; transcriptome sequencing of granulosa cells treated with DNAH6 siRNA was conducted to investigate the gene’s action mechanism. The analysis indicated that both MLM and CMLM models identified a significant locus linked to the total number of piglets born, with the SNP positioned at 3-60064515, associated with the DNAH6 gene. Disruption of the DNAH6 gene notably reduced the proliferation of ovarian granulosa cells (p < 0.05). Transcriptome sequencing results suggest that DNAH6 may support the normal transcriptional activity of the cAMP signaling pathway by maintaining EP300 and CREBBP expression in porcine ovarian granulosa cells, while potentially inhibiting the anti-proliferative effects of the FoxO pathway. This potential mechanism may help sustain the proliferative ability of granulosa cells and promote normal follicular development, which may ultimately contribute to an increase in the total number of piglets born in sows. These results offer a potential candidate marker for enhancing the total number born of French Large White sows. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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27 pages, 7409 KB  
Article
A CAF-Associated Stromal Remodeling Signature Links Immune Exclusion to Exhaustion-Prone CD8+ T-Cell Dysfunction in High-Grade Serous Ovarian Cancer
by Yang Bai, Ruifang Chen and Xin Lu
Int. J. Mol. Sci. 2026, 27(13), 6092; https://doi.org/10.3390/ijms27136092 - 7 Jul 2026
Viewed by 513
Abstract
High-grade serous ovarian carcinoma (HGSOC) shows limited benefit from immune checkpoint blockade, partly because stromal barriers impair antitumor immunity. We developed a cancer-associated fibroblast (CAF)-associated mitochondrial metabolic and matrix-remodeling signature, termed CMMS, to characterize this immune-suppressive stromal state. CMMS integrated contractile/myCAF, extracellular matrix [...] Read more.
High-grade serous ovarian carcinoma (HGSOC) shows limited benefit from immune checkpoint blockade, partly because stromal barriers impair antitumor immunity. We developed a cancer-associated fibroblast (CAF)-associated mitochondrial metabolic and matrix-remodeling signature, termed CMMS, to characterize this immune-suppressive stromal state. CMMS integrated contractile/myCAF, extracellular matrix (ECM), and mitochondrial metabolic genes. Its clinical, metabolic, and immune relevance was evaluated in TCGA-HGSOC, independent GEO cohorts, single-cell RNA-seq datasets, and an anti-PD-L1-treated cohort, followed by cell–cell communication and experimental validation. LASSO-weighted CMMS stratified overall survival, with high CMMS indicating poorer prognosis. CMMS-high tumors exhibited ECM/TGFβ activation; associations with COL1A1, POSTN, and LOX; and a hypoxia-dominant metabolic phenotype. Mediation analysis suggested that hypoxia largely linked CMMS to glycolytic remodeling. Immune profiling revealed stromal-rich immune exclusion, checkpoint activation, and exhaustion-prone T-cell dysfunction. Single-cell analysis localized CMMS mainly to myCAF-like ECM-remodeling CAFs. In validation datasets, CMMS-high CAFs were associated with reduced CD8 abundance, increased CD8 exhaustion, and stronger matrix- and chemokine-related communication with T cells. Experiments further supported a link between TGFβ-related fibroblast activation, ECM-remodeling features, and impaired CD8+ T-cell effector function. Overall, CMMS defines a CAF-enriched fibrotic–hypoxic stromal program associated with immune exclusion-related features, exhaustion-prone T-cell dysfunction, and poor outcome in HGSOC. Full article
(This article belongs to the Section Molecular Immunology)
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31 pages, 21851 KB  
Article
Effects of Water Avoidance Stress as a Psychological Stress Model and Coenzyme Q10 on Reproductive, Endocrine, and Ovarian Responses in Adult Female Rats
by Ahmet Yardimci, Tugrul Ertugrul, Ebru Gokdere, Feyza Keskin Buyukbudak, Meryem Sedef Dogru, Ahmet Tektemur, Zeliha Irem Turk, Nazife Ulker Ertugrul, Serife Tutuncu and Sinan Canpolat
Animals 2026, 16(13), 2093; https://doi.org/10.3390/ani16132093 - 6 Jul 2026
Viewed by 485
Abstract
Psychological stress can affect female reproductive function through behavioral, endocrine, ovarian, and oxidative mechanisms. Antioxidant supplements have therefore attracted attention for their potential to mitigate stress-related reproductive alterations. Coenzyme Q10 (CoQ10) is a lipid-soluble quinone involved in mitochondrial energy metabolism and is widely [...] Read more.
Psychological stress can affect female reproductive function through behavioral, endocrine, ovarian, and oxidative mechanisms. Antioxidant supplements have therefore attracted attention for their potential to mitigate stress-related reproductive alterations. Coenzyme Q10 (CoQ10) is a lipid-soluble quinone involved in mitochondrial energy metabolism and is widely used as a dietary supplement. However, whether CoQ10 modulates female reproductive responses to repeated psychological stress remains unclear. Although water avoidance stress (WAS) is a well-established psychogenic stress model, its effects on female reproductive outcomes are still not fully defined. In this study, we examined how repeated WAS affects female reproductive outcomes and whether CoQ10 modifies these effects. Twenty-eight regularly cycling female rats were assigned to sham control, WAS, CoQ10, or WAS + CoQ10 groups. WAS was applied for 1 h/day for 10 days, and CoQ10 was administered orally at 100 mg/kg/day. Repeated WAS did not significantly alter sexual incentive motivation parameters, reproductive hormones, corticosterone, total antioxidant capacity (T-AOC), 8-hydroxy-deoxyguanosine (8-OHdG), or mast cell count under the present experimental conditions (all p > 0.05). However, WAS reduced male-directed active investigation time (p = 0.008) and male investigation preference ratio (p = 0.024), increased absolute ovarian and adrenal gland weights (p = 0.035 and p = 0.016, respectively), reduced primordial follicle number (p = 0.030), decreased germinative epithelium thickness (p = 0.017), lowered VEGF histoscore (p = 0.033) regardless of CoQ10 treatment, and reduced corpus luteum angiogenesis in animals not receiving CoQ10 (p = 0.030). CoQ10 reduced total investigation time toward the male (p = 0.032), male investigation preference ratio (p = 0.037), 17-β estradiol (E2) (p = 0.003), testosterone (p = 0.021), and germinative epithelium thickness (p < 0.001) regardless of WAS exposure. CoQ10 also decreased kisspeptin-1 levels under non-stressed conditions (p = 0.010), while increasing corpus luteum angiogenesis under stress conditions (p = 0.003). Overall, repeated WAS produced selective behavioral and ovarian alterations rather than broad reproductive dysfunction. CoQ10 was not associated with a broadly protective or uniformly beneficial profile in this model, and its endocrine, behavioral, and ovarian effects should be interpreted with caution. Full article
(This article belongs to the Special Issue Health of the Ovaries, Uterus, and Mammary Glands in Animals)
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12 pages, 525 KB  
Article
Effects of Vitamin E on Growth Performance, Biochemical Indices, Antioxidant Capacity, and Ovarian Development in Female Chinese Sturgeon (Acipenser sinensis) Broodstock
by Pei Chen, Jing Yang, Baifu Guo, Yacheng Hu, Hongtao Huang, Wei Jiang, Zhiyuan Li and Kan Xiao
Animals 2026, 16(13), 2051; https://doi.org/10.3390/ani16132051 - 3 Jul 2026
Cited by 1 | Viewed by 405
Abstract
This study investigated the effects of dietary vitamin E (DL-α-tocopherol acetate) supplementation on growth performance, biochemical indices, antioxidant capacity, and ovarian development in female Chinese sturgeon (Acipenser sinensis) broodstock. A total of 180 healthy second-generation individuals (initial weight: 72.63 ± 3.64 [...] Read more.
This study investigated the effects of dietary vitamin E (DL-α-tocopherol acetate) supplementation on growth performance, biochemical indices, antioxidant capacity, and ovarian development in female Chinese sturgeon (Acipenser sinensis) broodstock. A total of 180 healthy second-generation individuals (initial weight: 72.63 ± 3.64 kg) were randomly distributed into three groups and fed isonitrogenous and isolipidic diets supplemented with 0 (V0), 1 (V1), or 2 (V2) g/kg vitamin E for 14 months. At the end of the trial, fish in the V2 group exhibited significantly higher final body weight, body length, and girth, demonstrating superior growth performance compared to the V0 and V1 groups (p < 0.05). Plasma antioxidant capacity was significantly enhanced in the V2 group, as indicated by elevated activities of catalase, superoxide dismutase, and total antioxidant capacity, alongside reduced levels of reactive oxygen species and malondialdehyde (p < 0.05). Biochemical analysis revealed that vitamin E supplementation significantly decreased plasma glucose, urea nitrogen, and alkaline phosphatase levels (p < 0.05), with the V2 group showing a notable increase in high-density lipoprotein cholesterol (p < 0.05). Ultrasonographic examination demonstrated that ovarian thickness in both transverse and longitudinal sections was significantly increased in the V2 group (p < 0.05). This morphological improvement was corroborated by significantly higher plasma levels of estradiol and vitellogenin in the supplemented groups, particularly in the V2 group. In conclusion, the current study revealed that dietary 2 g/kg vitamin E supplementation not only promoted growth performance and enhanced antioxidant capacity but also effectively stimulated ovarian development by modulating key reproductive hormones in female Chinese sturgeon broodstock. Full article
(This article belongs to the Special Issue Advances in Fish Reproduction and Development)
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