Search Results (183)

Megalobrama terminalis is a significant aquatic fish in South China, renowned for its tasty meat. Nonetheless, related studies are deficient concerning the gonadal development of M. terminalis. This paper presents the first comparative transcriptome analysis of the gonads of female and male M. terminalis. A total of 84,886 unigenes were assembled, with 42,322 effectively annotated to the Nr, SwissProt, KEGG, KOG, and GO databases. Furthermore, comparative transcriptomic analysis of M. terminalis was conducted to examine its gonadal development. A total of 14,972 differentially expressed genes (DEGs) were discovered. In the testis, the expression of 11,928 unigenes was significantly upregulated, while 3044 were significantly downregulated. Numerous DEGs associated with steroidogenesis, gonadal differentiation and development, and gametogenesis in teleost fish were identified. The results provide empirical support for further study of genes and pathways associated with sex determination and gonadal differentiation in teleost fish. Full article

This study elucidates the role of the steroidogenic acute regulatory protein (StAR) in sex steroid hormone dynamics and the gonadal development of the commercially important marine bivalve ark shell Scapharca broughtonii. The sequence of the StAR gene was obtained and verified from the transcriptome of ark shell, then the tissue localization and expression pattern during the gonad development of the StAR gene were detected by in situ hybridization and quantitative real-time PCR, respectively. Additionally, the concentrations of three critical sex steroid hormones (progesterone, testosterone, and estradiol) were measured throughout gonadal development using enzyme-linked immunosorbent assay (ELISA). The results showed that the length of the coding region of StAR was 1446 bp, encoding 481 amino acids. The results of qRT-PCR showed that the expression of the StAR gene varied with gonadal development, increased from the early active stage to the development stage, and decreased from the mature stage to the spent stage. Notably, the expression level in ovaries was higher than that in testes, suggesting the potential involvement of StAR in sex differentiation and gonadal development. Additionally, the results indicated that progesterone, testosterone, and estradiol accounted for 80%, 10%, and 10% of the total hormone content in the gonads, respectively. Correlation analysis revealed a highly significant strong positive correlation between progesterone/estradiol levels and StAR gene expression, demonstrating that StAR serves as a key regulator in sex steroid hormone biosynthesis. These findings provide crucial molecular evidence for StAR-mediated steroidogenesis in bivalve reproduction, offering fundamental insights into invertebrate endocrinology. Full article

Recently, China has become a hotspot for farming golden pompano (Trachinotus ovatus), a commercially valuable marine fish. The genetic mechanisms underlying ovarian development, particularly those regulated by insulin-like growth factors (IGFs), remain poorly understood. Existing research on T. ovatus has focused primarily on growth metrics, developmental stages, and immune responses, leaving a critical gap in knowledge regarding the hepatic regulatory pathways activated by IGFs. In this study, differentially expressed genes (DEGs) were detected through RNA sequencing (RNA-Seq) and associated pathways in response to IGF treatment. Comparisons between the IGF1, IGF2, and IGF3 treated groups and the control revealed 113 (46 upregulated, 67 downregulated), 637 (567 upregulated, 70 downregulated), and 587 DEGs (273 upregulated, 314 downregulated), respectively. KEGG enrichment analysis highlighted key pathways that may be linked to ovarian growth and development, including biotin metabolism, biosynthesis of amino acids, drug-cytochrome p450 pathways, MAPK signaling, estrogen signaling pathways, ECM receptor interaction, steroid biosynthesis, and ovarian steroidogenesis. These findings advance our understanding of hepatic metabolic regulation in golden pompano via the IGF system and provide actionable insights for optimizing aquaculture practices and selective breeding programs for this species. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. Methods: Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein–protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). Results: Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. Conclusions: The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women. Full article

Background: Prolactin (PRL) is a key reproductive hormone that regulates follicular development through endocrine and paracrine mechanisms. However, its specific role in porcine follicular development remains unclear. Methods: In the in vivo experiments, follicular fluid and tissue cells were obtained from small (1–2 mm), medium (3–4 mm), and large (5–6 mm) porcine follicles. PRL levels in follicular fluid were measured by ELISA. The expression levels of genes and proteins related to follicular development were assessed using quantitative real-time PCR (RT-qPCR) and Western blotting (WB). In the in vitro experiments, CCK-8, RT-qPCR, and WB were used to detect the effects of different concentrations (0, 30, and 300 ng/mL) of recombinant porcine prolactin (prPRL) on granulosa cell (GC) proliferation, steroid hormone synthesis, and angiogenesis, and transcriptome sequencing was performed. Results: The PRL concentration was significantly higher in large follicles compared to small and medium follicles. During follicular development, expression levels of PRL, PRL receptor (PRLR), proteolytic enzymes (CTSD, MMP2, MMP14, and BMP-1), and angiogenic factors (VEGFA and FGF-2) increased and then decreased. Moreover, prPRL promoted GC proliferation, increased the expression of PCNA and cyclin D1, upregulated steroidogenesis-related genes CYP11A1 and 3β-HSD, and significantly enhanced the expression of key angiogenic factors VEGFA and FGF-2. RNA-seq analysis identified 226 differentially expressed genes (DEGs), which were mainly enriched in signaling pathways such as the Hippo, JAK/STAT, and Rap1 pathways. Conclusions: PRL may regulate porcine follicle development by affecting cell proliferation and angiogenesis in GCs through the Hippo, JAK/STAT and Rap1 signaling pathways. Full article

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with a high mortality and poor prognosis. To elucidate the genetic underpinnings of ACCs, we have analyzed the transcriptome profiles of ACC tumor samples from patients enrolled in the TCGA and NCI cohorts. Methods: We developed a bimodal approach using Gaussian Mixture Models to identify genes with bimodal distribution in ACC samples. Among the 72 bimodally expressed genes that are used to stratify patients into prognostic groups, we focused on SEMA7A, as it encodes a glycosylphosphatidylinositol-anchored membrane glycoprotein (Semaphorin 7a) regulating integrin-mediated signaling, cell migration and immune responses. Results: Our findings reveal that high expression levels of SEMA7A gene are associated with poor prognosis (hazard ratio = 4.27; p-value < 0.001). In hormone-producing ACCs, SEMA7A expression is elevated and positively correlated with genes driving steroidogenesis, aldosterone and cortisol synthesis, including CYP17A1, CYP11A1, INHA, DLK1, NR5A1 and MC2R. Correlation analyses show that SEMA7A is co-expressed with the integrin-β1, FAK (focal adhesion kinase) and MAPK/ERK (mitogen-activated protein kinase/extracellular signal regulated kinases) signaling pathways. Immunohistochemistry (IHC) staining demonstrates the feasibility of evaluating SEMA7A in ACC tissues and shows a significant correlation between gene expression (RNA-Seq) and protein expression (IHC). Conclusions: These findings suggest SEMA7A as a candidate for further research in ACC biology and a candidate for cancer therapy, as well as a potential prognosis biomarker for ACC patients. Full article

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

Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 μM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 μM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 μM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations. Full article

Background/Objectives: The Changshun green-shell laying hen with a strong broodiness is a Chinese indigenous chicken breed. Little is known about the mechanisms responsible for the ovary development of Changshun green-shell laying hens from the egg-laying period (LP) to the incubation period (BP). Methods: A total of six hens were selected from LP (n = three) and BP (n = three) at 28 weeks old. The RNA sequencing (RNA-seq) of ovaries from hens in LP and BP groups was performed to identify candidate genes and pathways associated with broodiness. Results: We identified 1650 differently expressed genes (DEGs), including 429 up-regulated and 1221 down-regulated DEGs, in chicken ovaries between LP and BP groups. Gene ontology term (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEGs were mainly involved in the pathways related to follicle development in chicken ovaries, including focal adhesion, the MAPK signaling pathway, and the FoxO signaling pathway, and vascular smooth muscle contraction, ECM–receptor interaction, and the GnRH signaling pathway were down-regulated in incubating ovaries. Eight candidate genes (EGFR, VEGFRKDRL, FLT1, KDR, PDGFRA, TEK, KIT and FGFR3) related to angiogenesis, folliculogenesis, steroidogenesis and oogenesis in ovaries were suggested to play important roles in the ovarian development of Changshun hens during the transition from LP to BP. Conclusions: This study identified a range of genes and several pathways that may be involved in regulating the broodiness of Changshun green-shell laying hens. These data are helpful to further enrich our understanding of the mechanism of incubation behaviour in chickens. Full article

Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. Full article

In small ruminants, laparotomy for ovarian exploration followed by oocyte collection has been progressively replaced by laparoscopic puncture of follicles, which has become an important method for obtaining oocytes in vivo. However, the superovulation protocols and collection frequency used for laparoscopic ovum pick-up (LOPU) in sheep still require further investigation. This study explored the factors influencing LOPU efficiency in sheep, including Controlled Internal Drug Release (CIDR) for estrus synchronization, FSH source and dose, and recovery intervals. The optimal superovulation protocol (using the CIDR device, a total of 16 mg of long-acting recombinant ovine FSH (LR-FSH) administered in two doses, and a one-month interval between LOPU sessions) was subsequently identified. Ovarian follicles were collected via LOPU from Hu sheep and Altay sheep for transcriptomic and metabolomic sequencing to explore interbreed differences in follicular development. The results indicated that LOPU efficiency was significantly higher in the CIDR group (p < 0.05) and with a 30-day recovery interval (p < 0.05). No significant differences in LOPU efficiency were observed between FSH sources or hormone doses. Furthermore, Hu sheep exhibited significantly higher LOPU efficiency and more antral follicles than Altay sheep. Transcriptomic analysis of follicular contents and metabolomic profiling of follicular fluid revealed that differentially expressed genes and metabolites were primarily enriched in pathways related to steroidogenesis, amino acid metabolism, and fatty acid metabolism. This study provides an optimized treatment protocol to enhance LOPU efficiency and integrates multi-omics analyses to elucidate the molecular mechanisms underlying follicular development differences among various breeds. Full article

The cryopreservation of oocytes through vitrification is imperative for the conservation of livestock germplasm resources. However, as oocytes exhibit significant oxidative stress and organelle damage following vitrification freezing, it is crucial to optimise the vitrification conditions to mitigate the deleterious effects of freezing. In this study, we demonstrated that spermidine has been showed to enhance oocyte survival after vitrification freezing (92% ± 4% vs. 82% ± 3%, p < 0.01) and blastocyst formation after freezing for in vitro fertilisation (14.86% ± 7% vs. 6% ± 3, p < 0.05). Spermidine supplementation rescued 47.3% of dysregulated pathways, including ovarian steroidogenesis, and restored normal expression levels in 43.3% of aberrantly expressed genes. Subsequent studies elucidated that spermidine effectively rescued mitochondrial dysfunction after vitrification, alleviated oxidative stress damage, and regulated intracellular calcium homeostasis. Consequently, we concluded that the addition of spermidine during vitrification freezing is an effective method to protect oocytes from freezing damage. 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

Ozone, a critical air pollutant, has been shown to lead to systemic inflammation that can alter bodily functions, including hormone secretion, fertility, and the hypothalamic–pituitary–gonadal (HPG) axis. This study aimed to quantify changes in hormone production and follicle development after acute exposure to ozone using an animal model to identify the potential mechanisms underlying the observed effects of air pollution exposures on fertility and hormone secretion. To accomplish this, regularly cycling 8-week-old female C57BL/6J mice were exposed to 2 ppm of ozone or filtered air (control) for 3 h on the day of proestrus. Blood, ovaries, brain tissues, and pituitary glands were collected at 4 h after exposure to evaluate hormone levels, ovarian follicle distribution, and gene expression. Ovaries were also harvested at 24 h post-exposure. We found that at 4 h after ozone exposure, mice had significantly higher (30%) circulating estradiol levels than mice exposed to filtered air. This effect was accompanied by a decrease in mRNA expression of gonadotropin genes (LH, FSH) and gonadotropin-releasing hormone in the pituitary gland. Analysis of ovarian tissue at 4 h and 24 h after exposure showed no significant changes in follicle composition or the expression of steroidogenesis genes. We conclude that acute ozone exposure affects sex hormone levels and disrupts the HPG axis. Future studies addressing chronic or long-term effects of air pollution exposure are needed to elucidate the mechanisms by which ambient ozone affects endocrine function. Full article