Search Results (85)

Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10⁻⁷) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r² = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome. Full article

The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in regulating female reproductive traits, particularly litter size, in small ruminants, such as sheep and goats. This review comprehensively examines the molecular mechanisms through which TGF-β superfamily members—including bone morphogenetic proteins (BMPs), growth differentiation factor 9 (GDF9), inhibin (INHA and INHB), and associated signaling genes—influence ovarian follicular development, ovulation rate, and ultimately, litter size. We synthesize recent findings on polymorphisms in key genes, such as BMPR1B, BMP15, GDF9, inhibins and SMADs family genes, across diverse sheep and goat breeds worldwide. The manuscript highlights how specific mutations in these genes create an intricate signaling network that modulates granulosa cell proliferation, follicular sensitivity to FSH, and the prevention of dominant follicle selection. These molecular interactions result in increased ovulation rates and larger litter sizes in prolific breeds. The gene dosage effects observed in heterozygous versus homozygous mutation carriers further illuminate the complex nature of these reproductive regulations. This improved the understanding of the genetic basis for prolificacy provides valuable insights for marker-assisted selection strategies aimed at enhancing reproductive efficiency in small ruminant breeding programs, with significant implications for improving livestock productivity and economic outcomes. Full article

Overexploitation is the main anthropogenic threat to groupers (Epinephelidae) that aggregate to spawn. Fishing negatively affects their reproductive success and indirectly harms fishery economic yield. In the southern Gulf of Mexico, grouper catches, which include thirteen species, are in decline. A lack of biological information on each exploited species prevents optimising fishery management. Using histological examination of the gonads, the reproductive traits of red hind Epinephelus guttatus and yellowfin grouper Mycteroperca venenosa were studied from January 2008 to October 2009. Collections were made at two reef systems (Alacranes Reef and Bajos del Norte) on the continental shelf of the Yucatan Peninsula, Mexico, where these species form transient spawning aggregations. The results confirmed that previously identified spawning aggregation sites at both reefs constitute productive seasonal and perennial “hotspots” for both groupers; they spawn annually between January and April. Females of these protogynous hermaphroditic species exhibit a reproductive strategy characterised by asynchronous ovarian development organisation and ovulation. Sex ratios and maximum sizes at each reef suggest that populations of both groupers had a good conservation status as of the late 2000s. Both reefs are now marine protected areas, and a discussion is made of the consequent possible benefits to grouper population conservation and sustainability in the southern Gulf of Mexico. Full article

The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter sheep) and Ujumuqin sheep (single-litter sheep) as comparative models, constructed the expression profiles of ncRNAs and mRNAs in ovarian tissues, identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and performed target gene prediction along with functional and signaling pathway enrichment analyses. Reproduction-related pathways were further screened to construct competing endogenous RNA (ceRNA) regulatory networks (lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA). Finally, the dual-luciferase reporter gene assay system was employed to perform the functional validation of the relevant targeted regulatory effects. A comprehensive screening identified 411 DE lncRNAs, 322 DE circRNAs, 26 DE miRNAs, and 29 DEGs from the ovarian tissues of Ujumqin and Small-Tail Han sheep. The results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the DE target genes were significantly enriched in pathways associated with cell dedifferentiation, the positive regulation of embryonic development, glycosaminoglycan biosynthesis, Hippo signaling, and other signaling pathways. To identify genes associated with reproductive processes, we performed differential expression screening followed by pathway enrichment analysis, which revealed significant enrichment in reproductive regulatory pathways. Based on these findings, we constructed a ceRNA regulatory network incorporating 22 DEGs, 17 DE lncRNAs, three DE circRNAs, and one DE miRNA. Our analysis revealed that oar-let-7a is involved in signaling pathways such as oocyte meiosis and Hippo, suggesting it may serve as a key miRNA regulating the trait of multiple offspring. The dual-luciferase reporter assay was employed to confirm that oar-let-7a directly targets and regulates the expression of CPEB1. Additionally, it was demonstrated that circRNA803 and lncRNA MSTRG.19726 function as molecular sponges to competitively bind and regulate oar-let-7a. These findings suggest that oar-let-7a mediates the expression of CPEB1 via circRNA803 and lncRNA MSTRG.19726 sponge adsorption, thereby regulating the process of follicular dominance in sheep. The qRT-PCR method was employed to validate the expression patterns of nine randomly selected DEGs, and the results corroborated the reliability of the RNA-seq sequencing data. This study investigated the coordinated regulatory mechanism of DE ncRNAs and their corresponding target genes, identifying a ceRNA network, circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1, which plays a critical role in regulating the process of follicular dominance in sheep. These findings provide fundamental data for uncovering the reproductive potential of sheep and facilitate a comprehensive understanding of their reproductive characteristics, which hold significant guiding implications for enhancing reproductive efficiency. Full article

Optimal litter size on goat farms is an important trait for production and economic efficiency. The ovary and uterus, key components of the reproductive system, play essential roles in reproductive performance. In recent years, numerous genes linked to goat reproductive performance have been identified. However, reliable marker genes that are specifically associated with litter size require further exploration. In this study, eight Jining Grey goats were divided into high-yield (n = 4) and low-yield (n = 4) groups on the basis of their kidding records to identify key regulatory genes associated with litter size. Ovarian and uterine tissues were collected during oestrus for RNA sequencing (RNA-seq). After two outlier uterine tissue samples were excluded, the remaining 14 samples were subjected to WGCNA and differential expression gene (DEG) analysis. A total of 1224 DEGs were identified (|log2(fold change) ≥ 1|, p ≤ 0.05), including 912 in ovarian tissues (monozygotic vs. polyzygotic, MO vs. PO) and 312 in uterine tissues (MU vs. PU). Through WGCNA, we identified 15 coexpression modules, among which four key modules were significantly correlated with litter size. Our analysis focused on the magenta and green modules, as they contained 11 and 3 candidate genes overlapping with the DEGs, respectively. Notably, three genes—FOXC1, FOSB, and FGL2—were found to play important roles in both ovarian and uterine tissues. These genes mainly participate in regulatory processes such as RNA polymerase II transcription factor activity, calcium ion binding, and extracellular space organization, highlighting their potential as key candidates for future research. Overall, we identified several gene modules associated with litter size in goats, providing potential molecular markers for investigating litter size traits in Jining Grey goats. Full article

Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetics. Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with in silico follow-up. Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with p < 5 × 10⁻⁸ associated with at least one of the cancer types at p < 10⁻³ and one of the autoimmune/autoinflammatory diseases at p < 10⁻³. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping led variants to nearest genes as putative functional targets and focusing on immune-related genes implicated 32 genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1, IKZF1, SPI1, SH2B3, LAT) was each strongly correlated (Spearman’s ρ > 0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4, CD8A, CD11B, CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via the expression of quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable. Conclusions: We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded by IRF1, IKZF1, SPI1, SH2B3 and LAT as possible targets for cancer immunotherapy. Full article

Ovarian tissue is critical for goose reproduction. This study aimed to investigate gene regulation by DNA methylation in relation to the reproductive traits of geese. We performed whole-genome bisulfite sequencing (WGBS) on ovarian tissues from Sichuan white geese (high-laying-rate group: HLRG, ♀ = 3; low-laying-rate group: LLRG, ♀ = 3) during the laying period. The results showed a higher level of hypermethylated differentially methylated regions (DMRs) in the HLRG, indicating a higher overall methylation level compared to the LLRG. In total, we identified 2831 DMRs and 733 differentially methylated genes (DMGs), including 363 genes with upregulated methylation. These DMGs were significantly enriched in pathways related to microtubule function (GO:0005874; GO:0000226), GnRH secretion, thyroid hormone signaling, ECM-receptor interaction, and PI3K–Akt signaling. Integration with RNA-seq data identified eight overlapping genes between DMGs and differentially expressed genes (DEGs), with five genes (CUL9, MEGF6, EML6, SYNE2, AK1BA) exhibiting a correlation between hypomethylation and high expression. EML6, in particular, emerged as a promising candidate, potentially regulating follicle growth and development in Sichuan white geese. Future studies should focus on further verifying the role of the EML6 gene. In conclusion, this study provides important insights into the regulatory mechanisms of DNA methylation influencing reproductive traits in geese, offering novel candidate markers for future goose breeding programs. Full article

Reproduction and breeding are crucial to maintaining abalone aquaculture. Understanding the molecular underpinnings of sexual maturation is essential for advancing knowledge in reproductive biology. However, the molecular mechanisms of gonadal development in abalones remain poorly understood, particularly in microRNA (miRNA)-mediated regulation. Thus, this study conducted a comprehensive transcriptomic analysis of abalone Haliotis discus hannai (H. discus hannai) to identify genes and miRNAs associated with ovarian and testicular discovery. This study identified 685 differentially expressed (DE) genes between the H. discus hannai ovary (DD_ovary) and testis (DD_testis) groups, comprising 479 upregulated and 206 downregulated genes in the DD_ovary. Moreover, 137 miRNAs, including 83 novel and 54 known miRNAs, were detected, with 30 upregulated and 27 downregulated in the DD_ovary compared to the DD_testis. Bioinformatics analysis revealed that these miRNAs regulate key processes such as carbohydrate metabolic processes, kinase and hydrolase activity, and starch and sucrose metabolism, all potentially associated with reproductive traits. Further, key mRNA candidates, including Vitelline envelope sperm lysin receptor (Verl) and Testis-specific serine/threonine-protein kinase (Tssk) 1, and miRNAs such as novel_90 and novel_120, were identified as components of a functional miRNA-mRNA network associated with sexual maturity and sex determination. These key genes were verified using qRT-PCR and fluorescence in situ hybridization (FISH). These transcriptomic and miRNA datasets provide valuable resources for understanding abalone reproductive biology and may support molecular breeding strategies. Full article

Gestation length (GL) is a critical indicator of reproductive performance in sows and is closely associated with other reproductive traits, such as total number born (TNB) and number born alive (NBA). Despite its importance, the genetic mechanisms underlying GL and its impact on reproductive traits remain poorly understood. In this study, we investigated the relationship between GL and reproductive traits using 7013 farrowing records and conducted an imputed whole-genome sequence-based genome-wide association study (GWAS) for GL in first-parity sows, involving 3005 French Large White sows. Our findings revealed that the heritability of GL ranged from 0.22 to 0.26. Both excessively short and long GLs were associated with negative impacts on TNB, NBA, and other reproductive traits. A total of 64 SNPs exceeded the significance threshold, leading to the identification of two novel quantitative trait loci (QTLs) on chromosome 5 (QTL-1: 15.29–15.39 Mb and QTL-2: 12.86–12.94 Mb) and three promising candidate genes: TROAP, RFX4, and ADCY6. Gene ontology and KEGG pathway enrichment analyses revealed that these candidate genes are enriched in key biological processes, including ovarian steroidogenesis, the GnRH signaling pathway, and the regulation of cAMP biosynthesis, all of which are crucial for gestation and pregnancy maintenance. These findings improve our understanding of the genetic architecture of GL in sows and offer valuable genetic markers for enhancing reproductive efficiency in breeding programs. Full article

Onychostoma macrolepis is not only a protected Cyprinid species in the wild but also an emerging commercial aquaculture fish in China. The objective of this research was to genetically modify the genes associated with commercial traits by CRISPR/Cas9 for the protection and utilization of the germplasm resources of O. macrolepis. To that end, one-cell stage embryos were obtained via hormone-induced ovulation and artificial insemination in O. macrolepis. Eight genes related to body color, growth, intermuscular bone, and sex differentiation were mutated in O. macrolepis using the CRISPR/Cas9 system by microinjection of gRNA/Cas9 mRNA. The optimal dose of gRNA/Cas9 mRNA was determined by injection of different concentrations of tyr (tyrosinase)-gRNA/Cas9 and examination of the mutation rate and hatching rate of embryos. Indels were detected by T7 endonuclease I digestion and Sanger sequencing. F0 mutants with high mutation rates were selected for phenotype analyses. Disruption of body color gene tyr, mpv17 (mitochondrial inner membrane protein MPV17), and csf1ra (colony-stimulating factor 1 receptor, a) resulted in obvious phenotype with decreased or even absence of melanophores, iridophores, and xanthophores, respectively. Mutation of mstnb (myostatin b) led to improved growth performance. Mutation of mc4r (melanocortin 4 receptor) led to no obvious phenotype. Mutation of runx2b (RUNX family transcription factor 2b) and bmp6 (bone morphogenetic protein 6) resulted in decreased or absence of intermuscular bones, as revealed by alizarin red S staining. Mutation of cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a) resulted in ovarian degeneration as revealed by gonadal histological examination. Therefore, this study successfully obtained mutants with obvious phenotypes of genes associated with body color, growth, intermuscular bone, and sex differentiation by CRISPR/Cas9 in O. macrolepis. Full article

Ovarian cancer (OC) is the second most common female reproductive cancer and the most lethal gynecological malignancy worldwide. Most human OCs are characterized by high rates of drug resistance and metastasis, leading to poor prognosis. Improving the outcomes of patients with relapsed and treatment-resistant OC remains a challenge. This study aimed to investigate the role of epidermal growth factor-like domain 8 (EGFL8) in human OC by examining the effects of siRNA-mediated EGFL8 knockdown on cancer progression. EGFL8 knockdown in human OC cells promoted aggressive traits associated with cancer progression, including enhanced proliferation, colony formation, migration, invasion, chemoresistance, and reduced apoptosis. Additionally, knockdown upregulated the expression of epithelial–mesenchymal transition (EMT) markers (Snail, Twist1, Zeb1, Zeb2, and vimentin) and cancer stem cell biomarkers (Oct4, Sox2, Nanog, KLF4, and ALDH1A1), and increased the expression of matrix metallopeptidases (MMP-2 and MMP-9), drug resistance genes (MDR1 and MRP1), and Notch1. Low EGFL8 expression also correlated with poor prognosis in human OC. Overall, this study provides crucial evidence that EGFL8 inhibits the proliferation and cancer aggressiveness of human OC cells by suppressing ERK/MAPK signaling. Therefore, EGFL8 may serve as a valuable prognostic biomarker and a potential target for developing novel human OC therapies. Full article

The astringent selection criteria for milk-oriented traits in dairy cattle have rendered these animals prone to various metabolic disorders. Postpartum lactational peak and reduced feed intake lead to negative energy balance in cattle. As a compensatory mechanism, cattle start mobilizing fat reserves to meet the energy demand for vital body functions. Consequently, diminished glucose concentrations and elevated ketone body levels lead to poor ovarian function. The impaired follicular development and subpar oocyte quality diminish the conception rates, which poses significant economic repercussions. Follicular fluid is integral to the processes of follicular growth and oocyte development. Hence, the present study was performed to identify potential alterations in metabolites in the follicular fluid under in vitro culture conditions mimicking negative energy balance. Our results revealed nine distinct metabolites exhibiting differential expression in follicular fluid under negative energy balance. The differentially expressed metabolites were predominantly associated with pathways related to amino acid metabolism, lipid metabolism, signal transduction mechanisms, and membrane transport, alongside other biological processes. The identified signature metabolites may be further validated to determine oocyte fitness subjected to in vitro fertilization or embryo production from slaughterhouse source ovaries. Full article

Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. Methods: A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Results: Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. Conclusions: The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses. Full article

Ovarian development significantly influences the laying performance of geese. In this study, the transcriptome analysis was conducted on the ovarian tissues of Wanxi White Geese during the pre-laying (KL), laying (CL), and ceased-laying period (XL). Short Time-series Expression Miner (STEM) analysis and miRNA–mRNA regulatory network construction were performed to identify the key genes and miRNAs regulating laying traits. Comparative analysis of KL vs. CL, CL vs. XL, and XL vs. KL groups resulted in the identification of 337, 136, and 525 differentially expressed genes (DEGs), and 258, 1131, and 909 differentially expressed miRNAs (DEMs), respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis (p < 0.05) revealed that the main enrichment pathways of DEGs and DEMs at different breeding periods were Neuroactive ligand–receptor interaction, GnRH signaling pathway and Wnt signaling pathway, all associated with ovarian development. According to the three groups of common pathways, four DEGs were screened out, including INHBB, BMP5, PRL, and CGA, along with five DEMs, including let-7-x, miR-124-y, miR-1-y, and miR-10926-z, all of them may affect ovarian development. A miRNA–mRNA regulatory network was constructed through integrated analysis of DEGs and DEMs, revealing nine miRNAs highly associated with ovarian development: miR-101-y, let-7-x, miR-1-x, miR-17-y, miR-103-z, miR-204-x, miR-101-x, miR-301-y, and miR-151-x. The dual-luciferase reporter gene verified the target relationship between WIF1 and miR-204-x, suggesting that these miRNAs may influence ovarian development in Wanxi White Goose by regulating the expression levels of their target genes within ovarian tissue. This study provides a theoretical foundation for analyzing the mechanisms of ovarian development across different breeding periods and accelerating the cultivation of new breeds through post-transcriptional regulation levels. Full article

The Taihe Black-Bone Silky Fowl (Gallus gallus domesticus Brisson) possesses significant value in terms of consumption, medicinal applications, and ornamental appeal, representing a precious genetic resource and traditional Chinese medicinal material. However, considerable variation exists within populations regarding egg-laying performance. This study integrates a whole-genome selection signal analysis (SSA) with a transcriptome analysis to identify genes associated with egg-laying traits in Taihe Black-Bone Silky Fowls. We identified 31 candidate genes under selection from the high-yield chicken (HC) and low-yield chicken (LC) groups. Additionally, through RNA-seq analysis, 257 common differentially expressed genes (DEGs) were identified from four comparative groups. Two overlapping genes—LPL and SETBP1—were found in both the selected gene and DEG lists. These selected genes and DEGs were enriched in pathways related to ovarian development, including the lysosome pathway, the ECM–receptor interaction pathway, the TGF-beta signaling pathway, the Wnt signaling pathway, the PPAR signaling pathway, and the glycerolipid metabolism pathway. These research findings contribute to the breeding of Taihe Black-Bone Silky Fowls with high egg production traits and provide a theoretical foundation for exploring the regulatory mechanisms of avian reproduction. Full article