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Keywords = FOXL-2

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13 pages, 2529 KiB  
Article
Cryopreservation of Ovarian Tissue at the Stage of Vitellogenesis from Yellow Drum (Nibea albiflora) and Its Effects on Cell Viability and Germ Cell-Specific Gene Expression
by Li Zhou, Feiyan Li, Zhaohan Sun, Jia Chen and Kunhuang Han
Fishes 2025, 10(6), 288; https://doi.org/10.3390/fishes10060288 - 12 Jun 2025
Viewed by 340
Abstract
The cryopreservation of ovarian tissues from fish has recently been carried out for several endangered and commercially valuable species. However, previous studies in this context have focused on the cryopreservation of immature ovaries—mainly through slow freezing and vitrification—which requires specialized freezing equipment or [...] Read more.
The cryopreservation of ovarian tissues from fish has recently been carried out for several endangered and commercially valuable species. However, previous studies in this context have focused on the cryopreservation of immature ovaries—mainly through slow freezing and vitrification—which requires specialized freezing equipment or higher cryoprotectant concentrations to keep cell viability. Therefore, the aim of this study was to explore a convenient, rapid, efficient and less toxic method for the cryopreservation of ovaries at the stage of vitellogenesis from yellow drum (Nibea albiflora), an economically important marine fish. The ovaries at the stage of vitellogenesis were isolated and cut into blocks of approximately 1 cm3, then cryopreserved with 15% propylene glycol (PG), fetal bovine serum (FBS) and 0.2 M trehalose as cryoprotectants. Finally, the samples were treated using three different freezing procedures, including a −80 °C refrigerator, liquid nitrogen, and their combination. After 7 days, the tissues were thawed and digested, and the cell survival rates and gene expression levels were detected using cell viability assay kits and qRT-PCR, respectively. The results of the viability assay showed that the procedure of ovarian tissue storage at −80 °C in a refrigerator for 1 h, followed by transfer to liquid nitrogen, resulted in the highest cell survival rate (>90%). Furthermore, the germ cells at various phases were of normal size; presented a full, smooth surface and regular shape; and did not show any signs of cell rupture, atrophy, depression, granulation or cavitation. Furthermore, the qRT-PCR results revealed that genes related to reproductive development, such as vasa, foxl2, zp3 and gsdf, were all down-regulated under the optimal protocol, while the expression of the nanos2 gene (which is specifically distributed in oogonia) maintained a higher level, similar to that in the control group. This indicated that the viability of germ stem cells (oogonia) was not weakened after freezing and that oogonia could be isolated from the cryopreserved ovaries for germ cell transplantation. The present study successfully establishes an optimal cryopreservation protocol for ovarian tissues from Nibea albiflora, providing reference for the preservation of ovaries at the stage of vitellogenesis from other species. Full article
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13 pages, 874 KiB  
Article
The Prognostic Value of FOXL2 Mutant Circulating Tumor DNA in Adult Granulosa Cell Tumor Patients
by Geertruid J. Brink, Nizar Hami, Hans W. Nijman, Jurgen M. J. Piek, Luc R. C. W. van Lonkhuijzen, Eva Maria Roes, Ward Hofhuis, Christianne A. R. Lok, Cor D. de Kroon, Eelke H. Gort, Petronella O. Witteveen, Ronald P. Zweemer and Jolijn W. Groeneweg
Cancers 2025, 17(11), 1894; https://doi.org/10.3390/cancers17111894 - 5 Jun 2025
Viewed by 571
Abstract
Objectives: The purpose of the study is to determine whether FOXL2 circulating tumor DNA can be used as a prognostic biomarker and marker for monitoring treatment response in patients with an adult-type granulosa cell tumor (aGCT). Methods: Plasma samples of patients included in [...] Read more.
Objectives: The purpose of the study is to determine whether FOXL2 circulating tumor DNA can be used as a prognostic biomarker and marker for monitoring treatment response in patients with an adult-type granulosa cell tumor (aGCT). Methods: Plasma samples of patients included in the multicenter GRANULOSA study were collected before and after surgery for primary or recurrent aGCT, during follow-up, and during systemic treatment. The presence of ctDNA containing the FOXL2 402C>G mutation was analyzed in 284 samples from 20 primary and 34 recurrent aGCT patients, using digital droplet PCR. Clinical data were retrieved from electronic patient records, and patients were followed through January 2025. Results:FOXL2 mutant ctDNA was detected in 28 of 54 patients (48%). In primary aGCT, recurrences were more frequently seen in patients with detectable ctDNA (33% vs. 18%), and ctDNA remained detectable postoperatively in some cases despite complete cytoreduction. In recurrent aGCT patients, detectable ctDNA was associated with significantly worse overall survival (p = 0.023), and the postoperative presence of ctDNA following complete debulking surgery was significantly associated with a shorter recurrence-free survival (4.7 vs. 11.6 months, p = 0.025). Conclusions:FOXL2 mutant ctDNA could be a prognostic biomarker in aGCT, being associated with worse overall survival in recurrent aGCT patients. In addition, the presence of ctDNA after surgery could reflect the presence of minimal residual disease, negatively impacting the disease course. The implementation of FOXL2 ctDNA measurement in clinical practice may help to identify high-risk aGCT patients. Full article
(This article belongs to the Special Issue Rare Gynecological Cancers)
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13 pages, 6770 KiB  
Article
Differential Expression Characteristics of Two Isoforms nr5a2f and nr5a2m in Gonadal Differentiation of Chinese Giant Salamanders, Andrias davidianus
by Dan Hu, Guanglve Li, Guohua Zou, Jiaqing Xu, Wenyin Luo and Qiaomu Hu
Animals 2025, 15(11), 1667; https://doi.org/10.3390/ani15111667 - 5 Jun 2025
Viewed by 366
Abstract
Nr5a2 (nuclear receptor subfamily 5, group a, member 2) is involved in gonad development and sex hormone synthesis. In this study, the full length of Nr5a2f and Nr5a2m were obtained by Nr5a2 variable splicing from Andrias davidianus, and the tissue distribution was [...] Read more.
Nr5a2 (nuclear receptor subfamily 5, group a, member 2) is involved in gonad development and sex hormone synthesis. In this study, the full length of Nr5a2f and Nr5a2m were obtained by Nr5a2 variable splicing from Andrias davidianus, and the tissue distribution was detected. We identified Nr5a2f of 2455 bp and Nr5a2m of 2150 bp length, encoding 479 and 325 amino, respectively. We first characterized Nr5a2f and Nr5a2m gene expression in developing gonads. Results showed that Nr5a2f had significantly high expression in the ovary and little expression in other tissues, during the sex differentiation and sex reversal, Nr5a2f expression was gradually decreased in the ovary and the expression in the testis was significantly lower than in the ovary from 1 year to 6 year old. Significantly high expression was observed in the ovary and reversal ovary, while low expression was in the testis and reversal testis. While Nr5a2m expression exhibited the opposite profile, high expression was observed in the brain and testis. During sex differentiation and sex reversal, high expression was shown in the testis and low expression in the ovary from one year to six years old and significantly higher expression emerged in testis and reversal testis than in ovary and reversal ovary. In situ hybridization, results showed that Nr5a2f began to express in female undifferentiated gonads and the expression level increased from 48 dpf to 91, while Nr5a2m was expressed in male undifferentiated gonads. Three RNA interference sites were designed and we detected that site 293 exhibited a significant inhibitory effect in ovary cells. After Nr5a2f expression was inhibited by site 293, we observed that female-based gene Nr5a2f, foxl2 and cyp19 expression were decreased, while the male-based gene dmrt1 and cyp17 expression was increased. These results suggested that Nr5a2f and Nr5a2m exhibited different expression patterns in the process of sex differentiation, which provided a foundation for further functional characterizations. Full article
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18 pages, 2450 KiB  
Article
The Potential Role of Gonadotropic Hormones and Their Receptors in Sex Differentiation of Nile Tilapia, Oreochromis niloticus
by He Gao, Hongwei Yan, Tomomitsu Arai, Chak Aranyakanont, Shuang Li and Shigeho Ijiri
Int. J. Mol. Sci. 2025, 26(11), 5376; https://doi.org/10.3390/ijms26115376 - 4 Jun 2025
Viewed by 645
Abstract
Nile tilapia, as an ideal model for studying sex differentiation, is a popular farmed fish worldwide with a stable XX/XY sex-determination system. In tilapia, ovarian differentiation is triggered by estradiol-17β (E2) production in undifferentiated gonads. In a previous study, we suggested that follicle-stimulating [...] Read more.
Nile tilapia, as an ideal model for studying sex differentiation, is a popular farmed fish worldwide with a stable XX/XY sex-determination system. In tilapia, ovarian differentiation is triggered by estradiol-17β (E2) production in undifferentiated gonads. In a previous study, we suggested that follicle-stimulating hormone (FSH) signaling might be involved in ovarian differentiation in Nile tilapia. In this study, we further investigated the role of FSH signaling in ovarian differentiation via aromatase expression, which converts testosterone to E2. Masculinization of XX fry by aromatase inhibitor or 17α-methyltestosterone leads to suppression of fshr expression. Feminization of XY fry by E2 treatment increased fshr expression from 15 days after hatching, when E2 treatment was terminated. XX tilapia developed ovaries harboring aromatase expression if fsh and fshr were double knockdowns by morpholino-oligo injections. Finally, the transcriptional activity in the upstream region of the aromatase gene (cyp19a1a) was further increased by FSH stimulation when HEK293T cells were co-transfected with foxl2 and ad4bp/sf1. Collectively, this study suggests that the role of FSH signaling is not critical in tilapia ovarian differentiation; however, FSH signaling may have a compensatory role in ovarian differentiation by increasing cyp19a1a transcription in cooperation with foxl2 and ad4bp/sf1 in Nile tilapia. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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25 pages, 14782 KiB  
Article
Genome-Wide Identification and Expression Analysis of Zona Pellucida (ZP) Gene Family in Cynoglossus semilaevis
by Kaili Zhang, Zhangfan Chen, Chengbin Gao, Xihong Li, Na Wang, Min Zhang, Haipeng Yan, Zhenxia Sha and Songlin Chen
Int. J. Mol. Sci. 2025, 26(11), 5346; https://doi.org/10.3390/ijms26115346 - 2 Jun 2025
Viewed by 602
Abstract
The Chinese tongue sole (Cynoglossus semilaevis) is a commercially important mariculture species; however, its fertilization and hatching rates under artificial conditions remain relatively low. Zona pellucida proteins (ZPs), which mediate sperm–egg binding, were previously identified as differentially expressed genes between newly [...] Read more.
The Chinese tongue sole (Cynoglossus semilaevis) is a commercially important mariculture species; however, its fertilization and hatching rates under artificial conditions remain relatively low. Zona pellucida proteins (ZPs), which mediate sperm–egg binding, were previously identified as differentially expressed genes between newly differentiated ovaries and testes in C. semilaevis. In this study, we identified 25 ZPs of C. semilaevis through genomic analysis and classified them into five subfamilies. All genes possessed a conserved ZP domain, characteristic of the gene family from mammals to teleosts. Among them, nine genes were highly expressed in ovary cells, with the expression levels increasing during ovarian development, while another three genes were predominantly expressed in liver cells. Protein–protein interaction analysis predicted that 12 ZPs interacted with key reproductive regulators such as Gdf9, Arid4a, Arid4b, and Rbl, which were involved in steroidogenesis, sperm–egg recognition, and folliculogenesis. Functional analyses using RNA interference revealed that Cszpc7-1 knockdown in ovarian cells led to the downregulation of cyp19a, esr2, bmp15, and adamts-1, while the expression of rbl, gnas, adgrl1, and adgrl2 was upregulated. In contrast, Cszpax1 knockdown resulted in decreased expression of cyp19a, foxl2, arid4a, and zeb1, along with upregulation of arid4b, ogg1, and gdf9. These results suggested that ZP genes might contribute to ovarian homeostasis by regulating steroid hormone synthesis, follicular development, and ovulation. This study contributed to a deeper understanding of the reproductive mechanisms of C. semilaevis and provided evolutionary insights into the functional divergence of the ZP gene family across teleosts. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 2170 KiB  
Article
Integrated Analysis of Differential Expression Profiles of miRNA and mRNA in Gonads of Scatophagus argus Provides New Insights into Sexually Biased Gene Expression
by Yaling Lei, Kaizhi Jiao, Yuanqing Huang, Yuwei Wu, Gang Shi, Hongjuan Shi, Huapu Chen, Siping Deng, Guangli Li, Wenjing Tao and Dongneng Jiang
Animals 2025, 15(11), 1564; https://doi.org/10.3390/ani15111564 - 27 May 2025
Viewed by 428
Abstract
The Scatophagus argus (S. argus) is a valuable aquaculture species in southern China, with females exhibiting significantly faster growth rates than males. However, the limited understanding of its sex determination and differentiation mechanisms poses challenges for sex-controlled breeding. MicroRNAs (miRNAs), key [...] Read more.
The Scatophagus argus (S. argus) is a valuable aquaculture species in southern China, with females exhibiting significantly faster growth rates than males. However, the limited understanding of its sex determination and differentiation mechanisms poses challenges for sex-controlled breeding. MicroRNAs (miRNAs), key post-transcriptional regulators, are known to modulate critical pathways governing sex determination and differentiation across several vertebrates. However, there is currently no research on miRNAs related to sex determination and differentiation in S. argus. In this study, we analyzed the expression profiles of miRNA and mRNA in the gonads of adult S. argus using high-throughput sequencing. Our analysis identified 2210 miRNAs, including 482 differentially expressed miRNAs (DEMs) between sexes. These DEMs targeted 3340 differentially expressed genes (DEGs), generating 13,773 regulatory interaction pairs. The expression of some DEGs related to sex determination and differentiation was found to be either positively or negatively correlated with expression of DEMs that might regulate them. The novel_miR_110/Foxl2, novel_miR_802/Gdf9, and novel_miR_1263/Gdf9 show opposing differential expression trends, whereas sar-miR-143-5p-4/Gsdf, sar-miR-143-5p-5/Gsdf, and novel_miR_379/Sox3 show consistent trends. The regulatory relationship between miRNA and gene in the gonads does not seem to be conserved among different fish species. This work advances our understanding of the molecular mechanisms underlying the sexual dimorphism of gonadal gene expression in S. argus. The identified miRNA–gene interactions may serve as potential targets for future sex-control strategies, contributing to advancements in aquaculture practices for this species. Full article
(This article belongs to the Section Animal Reproduction)
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18 pages, 7688 KiB  
Article
The Function of Heat Shock Transcription Factors in Sex Differentiation in Cynoglossus semilaevis
by Zhijie Li, Xuexue Sun, Haipeng Yan, Lijun Wang, Xihong Li, Na Wang, Min Wei and Wenteng Xu
Animals 2025, 15(10), 1443; https://doi.org/10.3390/ani15101443 - 16 May 2025
Viewed by 355
Abstract
Chinese tongue sole (Cynoglossus semilaevis) is an important marine fish in China. It has sexual dimorphism. The weight and growth rate of female fish are much greater than those of male fish. However, high temperatures can induce sex reversal in genetic [...] Read more.
Chinese tongue sole (Cynoglossus semilaevis) is an important marine fish in China. It has sexual dimorphism. The weight and growth rate of female fish are much greater than those of male fish. However, high temperatures can induce sex reversal in genetic female fish (ZW) to phenotypic male fish; thus, identifying the genetic elements involved in temperature perception will provide the molecular basis for sex control. The heat shock transcription factor (hsf) is known as an important component of temperature sensing and mediates the heat shock response in fish such as Danio rerio; however, its function in C. semilaevis is unclear. In this study, five hsf genes (hsf1, hsf2, hsf4, hsf5a, and hsf5b) were identified in tongue sole and found to be expressed in the gonads at different developmental stages, peaking from 7M to 1Y. Gonadal in situ hybridization revealed that hsf gene signals were mainly localized in germ cells, e.g., sperm in the testis and all-stage oocytes in the ovary. Upon high-temperature stimulation, the expression of the hsf gene in the gonads increased gradually with increasing stimulation time, but different hsf genes presented different response patterns. After the RNA interference of hsf in the testis and ovarian cell lines, a series of sex-related genes, such as foxl2 and dmrt1, significantly changed. In vivo RNA interference had an effect on the female gonads and mainly affected neurl3 expression. On the basis of these data, we speculate that hsf responds to temperature stimulation and plays an important role in sex differentiation. This study helps elucidate the relationship between temperature sensing and sex differentiation in C. semilaevis. Full article
(This article belongs to the Special Issue Sex Determination and Differentiation in Aquatic Animals)
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18 pages, 3873 KiB  
Article
Integrated Genomic and Transcriptomic Analysis Reveals a Transcription Factor Gene Set Facilitating Gonadal Differentiation in the Pacific Oyster Crassostrea gigas
by Yunwang Shen, Ziyi Wang, Yanglei Jia and Xiao Liu
Genes 2025, 16(5), 513; https://doi.org/10.3390/genes16050513 - 28 Apr 2025
Viewed by 475
Abstract
Background/Objectives: The Pacific oyster Crassostrea gigas has emerged as a promising model system for sex determination studies due to its complex reproduction strategy and sex reversal. Transcription factors (TFs) play crucial roles in sex determination and gonadal differentiation. Despite previous research revealing functions [...] Read more.
Background/Objectives: The Pacific oyster Crassostrea gigas has emerged as a promising model system for sex determination studies due to its complex reproduction strategy and sex reversal. Transcription factors (TFs) play crucial roles in sex determination and gonadal differentiation. Despite previous research revealing functions of several conserved sex-determining pathway genes, such as Dmrt1, Foxl2, and SoxH, little is known about the other essential TF regulators driving C. gigas gonadal differentiation and development. Methods: In this study, a systematic identification of TFs revealed 1167 TF genes in the C. gigas genome. Comparative transcriptome analysis of C. gigas female and male gonads demonstrated 123 differentially expressed TF genes. Results: The majority of these sex-related TF genes were up-regulated in female or male gonads from the inactive stage to the mature stage. Moreover, this TF gene set was deeply conserved and showed similar regulation in the Kumamoto oyster Crassostrea sikamea gonads, suggesting their important regulatory roles in gonadal differentiation and development in Crassostrea oysters. Furthermore, two BTB TF gene clusters were identified in the C. gigas genome, both of which were specifically expressed in the male gonad. Gene numbers of each BTB gene cluster showed significant variations among six Crassostrea species. Conclusions: To the best of our knowledge, this study provides the first report of the whole TF family in C. gigas. The sex-related TF gene set will be a valuable resource for further research aimed at uncovering TF gene regulatory networks in oyster sex determination and gonadal differentiation. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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14 pages, 9062 KiB  
Article
Effects of Treatment with a DNA Methyltransferase Inhibitor 5-aza-dC on Sex Differentiation in Medaka (Oryzias latipes)
by Xiaojuan Cui, Liumeiyang Xu, Nan Tian and Jianjun Peng
Int. J. Mol. Sci. 2025, 26(7), 3280; https://doi.org/10.3390/ijms26073280 - 1 Apr 2025
Cited by 1 | Viewed by 2526
Abstract
DNA methylation is a common epigenetic modification of DNA levels in the genome of eukaryotic cells, and an aberrant elevation of DNA methylation in gene promoter regions can inhibit gene expression. DNA methyltransferases (DNMTs) are involved in genomic DNA methylation, divided into maintenance [...] Read more.
DNA methylation is a common epigenetic modification of DNA levels in the genome of eukaryotic cells, and an aberrant elevation of DNA methylation in gene promoter regions can inhibit gene expression. DNA methyltransferases (DNMTs) are involved in genomic DNA methylation, divided into maintenance DNA methyltransferases and de novo methylases, which are expressed to different degrees in the testis and ovaries. 5-aza-2′-deoxycytidine (5-aza-dC) is a cytidine analog with a strong methylation inhibition. In this experiment, medaka fish fries were treated with 5-aza-dC at 0 μg/L, 50 μg/L, and 100 μg/L. It was found that 100 g/L concentration of 5-aza-dC inhibited both body length and body weight of the adult fish, while 50 g/L concentration had no significant difference. In addition, paraffin section observation and gonad index statistics showed that after 100 g/L concentration of 5-aza-dC treatment, the gonad index of female fish increased significantly, but the gonad index of male fish had no significant difference. And the development of sperms and ovaries was normal without significant difference. Finally, we found that 5-aza-dC not only significantly decreased the transcription levels of dnmt1 and dnmt3bb.1, but also significantly increased the expression levels of female-related genes such as foxl2, cyp19a1 and wnt4, and significantly decreased the expression levels of male-related genes such as dmrt1, sox9a and amh. The DNA methylation patterns of foxl2 and dmrt1 genes were altered. This work provides more references for understanding the mechanism of DNA methylation affecting sex determination in fish. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 6434 KiB  
Article
An Inducible CYP19A1 Excision Model for Sexual Differentiation in Chicken (Gallus gallus) via the CRISPR/Cas9 System
by Guangzheng Liu, Yixiu Peng, Zeyu Li, Xilin Zhu, Hongyan Sun, Guohong Chen, Qisheng Zuo, Yingjie Niu, Jiuzhou Song, Wei Han, Wanhong Wei, Bichun Li and Kai Jin
Vet. Sci. 2025, 12(4), 296; https://doi.org/10.3390/vetsci12040296 - 22 Mar 2025
Viewed by 733
Abstract
Aromatase, a crucial enzyme for estrogen synthesis, plays a vital role in gender determination and differentiation. This study aimed to establish an inducible knockout model of the chicken CYP19A1 gene, which encodes aromatase, to support gender control in chickens. We selected the most [...] Read more.
Aromatase, a crucial enzyme for estrogen synthesis, plays a vital role in gender determination and differentiation. This study aimed to establish an inducible knockout model of the chicken CYP19A1 gene, which encodes aromatase, to support gender control in chickens. We selected the most efficient sgRNA target site and constructed an inducible knockout model based on the Tet-on system. The knockout efficiency reached 80% with 20 μg/mL DOX induction in vitro. The encapsulation of the plasmid with PEI and injection into eggs achieved a knockout efficiency of 45% in ovo. qRT-PCR analysis revealed a significant downregulation of female-related genes (CYP19A1, FOXL2, ESR1) and upregulation of male-related genes (DMRT1, SOX9, AMH) in female chicken embryos after induction. Western blotting showed decreased protein expression of CYP19A1 and FOXL2, and increased SOX9 expression in female embryos post-DOX induction. Elisa detection further confirmed lower estradiol levels in the gonads of induced female embryos compared to normal and non-induced females. These findings demonstrate the successful establishment of an inducible knockout system for the CYP19A1 gene in chickens, providing theoretical and technical support for the creation of new breeding materials for gender control. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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15 pages, 5402 KiB  
Article
Comparative Transcriptomic Analysis of Male and Female Gonads in the Zig-Zag Eel (Mastacembelus armatus)
by Fangyu Cui, Yuanyuan Wang, Haiyan Liang, Yexin Yang, Zhiyong Jiang, Jiahuan Song, Chao Liu, Yuli Wu, Xidong Mu and Yi Liu
Fishes 2025, 10(3), 117; https://doi.org/10.3390/fishes10030117 - 6 Mar 2025
Viewed by 561
Abstract
The zig-zag eel (Mastacembelus armatus) is a unique economic fish species in China and exhibits significant dimorphism of male and female phenotypes. Cultivating all-male seedlings can significantly improve production efficiency. To investigate sex differentiation and gonadal development in M. armatus, [...] Read more.
The zig-zag eel (Mastacembelus armatus) is a unique economic fish species in China and exhibits significant dimorphism of male and female phenotypes. Cultivating all-male seedlings can significantly improve production efficiency. To investigate sex differentiation and gonadal development in M. armatus, high-throughput sequencing technology was used to analyze the transcriptomes of male and female gonads at different developmental stages, both before and after sex differentiation. We identified key genes involved in sex differentiation, male-specific differentially expressed genes (DEGs), including dmrt1, amh, sox9, gsdf, and dmrt2b, and female-biased DEGs, including foxl2, rspo1, gdf9, bmp15, and wnt4. GO and KEGG enrichment analyses revealed that signaling pathways such as MAPK, Wnt, and TGF-β play significant roles in sex differentiation in M. armatus. The expression levels of 13 sex-related genes, including dmrt1, sox9, amh, foxl2, rspo1, and wnt4, were determined by RT–qPCR in addition to RNA sequencing. RT-qPCR validation results were consistent with the transcriptomic data, confirming the reliability of our findings. This research provides valuable insights into the mechanisms of sex differentiation in M. armatus and lays a foundation for developing all-male populations in aquaculture. Full article
(This article belongs to the Special Issue Genetics and Breeding in Aquaculture)
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17 pages, 3839 KiB  
Article
Epigenetic Perspectives and Their Prognostic Value in Early Recurrence After Hepatocellular Carcinoma Resection
by Chang-Yi Lu, Ching-Pin Lin, Hsiang-Lin Lee, Pey-Jey Peng, Shao-Chang Huang, Meng-Rong Chuang and Yih-Jyh Lin
Cancers 2025, 17(5), 769; https://doi.org/10.3390/cancers17050769 - 24 Feb 2025
Cited by 1 | Viewed by 712
Abstract
Background/Objectives: The post-hepatectomy survival of patients with hepatocellular carcinoma (HCC) faces challenges due to high recurrence rates, especially early recurrence (ER). We investigated DNA methylation in HCC and developed a methylation-based model for ER prediction (MER). Methods: We studied HCC patients with ER [...] Read more.
Background/Objectives: The post-hepatectomy survival of patients with hepatocellular carcinoma (HCC) faces challenges due to high recurrence rates, especially early recurrence (ER). We investigated DNA methylation in HCC and developed a methylation-based model for ER prediction (MER). Methods: We studied HCC patients with ER within a year post-hepatectomy, comparing them to those who remained recurrence-free (RF) for 5 years. In a testing set, we examined genome-wide methylation profiles to identify differences between ER and RF. Validation in an independent cohort confirmed candidate markers using real-time quantitative methylation-specific PCR (qMSP). We constructed MER by incorporating identified gene methylation, clinical information, and serum protein marker, and evaluated its predictive performance using ROC analysis and Cox regression. Results: Distinct signatures of hypermethylation and hypomethylation were observed between ER and RF, as well as between cirrhotic and non-cirrhotic groups. Significant aberrant methylation pathways, including FGFR signaling, the PI3K network, and the MAPK pathway, were observed in non-cirrhotic ER patients. Conversely, cirrhotic ER patients showed notable associations with Wnt/β-catenin signaling, cell adhesion, and migration mechanisms. Through qMSP analysis, we identified ER-associated genes, including BDNF, FOXL2, LMO7, NCAM1, NEIS3, PLA2G7, and LTB4R. MER demonstrated strong predictive ability for ER, with an AUC of 0.855, surpassing current indicators such as AFP, tumor size, and BCLC stage. Combining different predictors resulted in heightened AUC values. Importantly, the inclusion of MER yielded to the highest AUC of 0.952, underscoring the substantial contribution of MER to predictive accuracy. Conclusions: This study discovered the involvement of aberrant DNA methylation in HCC with early recurrence. The MER outperforms clinicopathological predictors and achieves robust prediction capabilities in identifying patients at risk of ER. Full article
(This article belongs to the Section Cancer Pathophysiology)
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17 pages, 14593 KiB  
Article
Characterization and Differential Expression of Sex Genes in Adults of Tropical Gar (Atractosteus tropicus)
by Otilio Méndez-Marin, María de Lourdes Jiménez-Badillo, Carina Shianya Álvarez-Villagomez, Talhia Martínez-Burguete, Uriel Rodriguez-Estrada, Gloria Gertrudys Asencio-Alcudia, Graciela María Pérez-Jiménez, Gabriela Galindo-Cortés, Virgilio Eugenio Arenas-Fuentes, Rafael Martínez-García, Luis Daniel Jiménez-Martínez and Carlos Alfonso Alvarez-González
Fishes 2025, 10(3), 94; https://doi.org/10.3390/fishes10030094 - 23 Feb 2025
Viewed by 811
Abstract
The tropical gar (Atractosteus tropicus) is a primitive freshwater fish of significant commercial importance in southeastern Mexico. However, its population is in danger due to habitat loss and overexploitation. Cultivation emerges as a viable reproductive management strategy; yet further studies are [...] Read more.
The tropical gar (Atractosteus tropicus) is a primitive freshwater fish of significant commercial importance in southeastern Mexico. However, its population is in danger due to habitat loss and overexploitation. Cultivation emerges as a viable reproductive management strategy; yet further studies are crucial to understanding molecular markers guiding reproductive management, differentiation, and sexual maturation in this species. We analyzed the expression of five sex-related genes (foxl2, sox9, cyp17a1, dmrt1, and cyp19a1) in the brain, liver, and gonads of adult A. tropicus (four females and five males). Methodologically, we collected samples and conducted RNA extraction, cDNA synthesis, and gene expression analysis using qPCR. The gonadal histology provided morphological context that reveals that the differential expression of genes establishes differences between sexes. The sexual phenotype of females is observed with the high expression of dmrt1, while in males, there is a reduction in the expression of dmrt1 and high levels of sox9, foxl2, and cyp17a1. Our findings establish dmrt1 and cyp19a1 as potential sex biomarkers and provide a molecular basis for developing sexing protocols in A. tropicus. Full article
(This article belongs to the Special Issue Advances in Fish Reproductive Physiology)
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12 pages, 5452 KiB  
Review
Uterine Tumors Resembling Ovarian Sex-Cord Tumors (UTROSCTs): Case Report and Narrative Review of the Literature
by Guglielmo Stabile, Laura Vona, Maria Carmela Pedicillo, Elisabetta Antonucci, Davide Arrigo, Marco D’Indinosante, Matteo Bruno, Tamara Stampalija and Luigi Nappi
J. Clin. Med. 2025, 14(5), 1430; https://doi.org/10.3390/jcm14051430 - 20 Feb 2025
Viewed by 863
Abstract
Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are among the rarest types of uterine tumors. Diagnosis of a UTROSCT is often challenging. Imaging techniques such as ultrasound and MRI are limited in distinguishing UTROSCTs as their appearance is usually suggestive of uterine leiomyoma [...] Read more.
Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are among the rarest types of uterine tumors. Diagnosis of a UTROSCT is often challenging. Imaging techniques such as ultrasound and MRI are limited in distinguishing UTROSCTs as their appearance is usually suggestive of uterine leiomyoma or adenomyosis. Additionally, the value of a preoperative biopsy remains uncertain due to the heterogeneous composition of the tumor and the inadequacy of limited samplings. We present a rare case of UTROSCT in a 59-year-old woman and we have performed a narrative review of the literature on PubMed, Scopus, and Web of Science from 2000 to June 2024, identifying 133 cases. According to our review, at histological exam UTROSCTs are mainly composed of cells resembling ovarian sex-cord elements which are arranged in cords or trabeculae, typically with a mild cytologic atypia. The most expressed sex-cord differentiation markers include inhibin, calretinin, melan A, CD56, CD99, SF1, WT1, CD10, and FOXL2. For women who have completed their reproductive plans, a total hysterectomy with adnexectomy is an adequate treatment for tumors confined to the uterus. For younger patients who wish to preserve fertility, tumorectomy via hysteroscopy or laparoscopy is the preferred treatment option and the recurrence rates range from 5% to 30%. Treatments for recurrent disease include surgery, chemotherapy, and radiation therapy, often used in combination. Advancements in molecular profiling and immunohistochemistry will improve our ability to diagnose and manage this tumor. Such investigations will enhance prognostic stratification, facilitating more accurate predictions of biological behavior and recurrence risk. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Article
Molecular Characterization and Expression of unc-13d in the Sex Reversal of Monopterus albus
by Zitong Lian, Fang Meng, Xueping Xia, Junchao Fang, Haifeng Tian and Qiaomu Hu
Animals 2025, 15(2), 122; https://doi.org/10.3390/ani15020122 - 7 Jan 2025
Viewed by 1015
Abstract
Monopterus albus is a protogynous hermaphroditic fish that changes from female to male, but the underlying sex change mechanism remains as-yet unknown. In this study, we firstly cloned and characterized the sequence and protein structure of unc-13d of M. albus. We found that [...] Read more.
Monopterus albus is a protogynous hermaphroditic fish that changes from female to male, but the underlying sex change mechanism remains as-yet unknown. In this study, we firstly cloned and characterized the sequence and protein structure of unc-13d of M. albus. We found that the genomic structure of unc-13d was different from other species. Expression was detected in the developing gonad by applying qRT-PCR and in situ hybridization. We found that the expression of unc-13d in the ovotestis was higher than in the ovary and testes. A strong signal of unc-13d was detected in oocytes and granulosa cells in the ovary and spermatogonia and primary spermatocytes in the testes. We found that the promoter methylation of unc-13d was negatively correlated with gene expression in developing gonads, especially at site 114. A dual-luciferase assay was designed and revealed that dmrt1 regulates promoter activity opposite to foxl2. In summary, during sex reversal, DNA methylation affects the binding of the transcription factor dmrt1 and foxl2 in the promoter region through methylation and demethylation interactions to regulate the expression of unc-13d during gonadal development. Full article
(This article belongs to the Special Issue Sex Determination and Differentiation in Aquatic Animals)
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