Search Results (63)

The Kazakh horse represents a significant genetic resource within China’s equine population, characterized by notable resilience and an ability to thrive on coarse forage. Nevertheless, a decline in its numbers has been observed recently, making the improvement of its reproductive performance crucial for the preservation of this breed and the advancement of the related industry. In this study, testicular tissues from 1-year-old (pre-pubertal) and 2-year-old (post-pubertal) Kazakh horses were analyzed. miRNA sequencing was conducted on tissues from these age groups, followed by bioinformatics analyses to elucidate the functions of differentially expressed miRNAs (DEmiRNAs). The reliability of the sequencing data was subsequently verified using RT-qPCR. Analysis revealed 165 differentially expressed miRNAs (DEmiRNAs) in the testicular tissues between the two age groups. Of these, 118 DEmiRNAs (e.g., eca-miR-206 and eca-miR-2483) were significantly up-regulated (p < 0.05), and 47 DEmiRNAs (e.g., eca-miR-196a and eca-miR-211) were significantly down-regulated (p < 0.05). These DEmiRNAs were mainly implicated in biological processes including lipid metabolism and signal transduction. Their predicted target genes are potentially involved in key reproductive processes, notably testicular development and spermatogenesis. This study identifies candidate miRNAs and potential regulatory pathways associated with sexual maturation in Kazakh horses, providing a preliminary molecular basis for future functional validation and improvement of equine reproductive performance. Full article

Background/Objectives It is known that failure to gain sufficient bone during skeletal growth and maturation phases predisposes to the development of senile osteoporosis as age-related bone loss ensues. There is limited knowledge about factors that are necessary for the pubertal growth spurt and achievement of peak bone mass. Diminution or disappearance of Juvenile Protective Factors (JPFs) after a given maturational stage could contribute to the onset of age-related declines in a variety of physiological functions, including bone physiology. Methods With available pediatric platelet-poor plasma (PPP) and mesenchymal/skeletal stem cells (MSCs), we tested whether proteomics and RNA-seq methodology have potential for the discovery of novel regulators of pubertal skeletal growth. Results Our data demonstrate that pediatric PPP rejuvenates age-related compromised MSC functions; that Mass Spectrometry (MS)-based proteomics identified known and novel circulating tissue growth/trophic factors in human PPP of pubertal, as compared with pre-pubertal, and post-pubertal subjects; and that the unbiased RNA-Seq approach revealed new genes and networks of genes that are dramatically elevated or diminished in pubertal MSCs. Conclusions The findings support the hypothesis that the characterization of pro-osteogenic JPFs could lead to the identification of novel therapeutic approaches to promote bone health in the elderly and of potential treatment regimens for senile osteoporosis. Full article

Deoxynivalenol (DON) is a common mycotoxin linked to ovarian oxidative stress, toxicity, and reduced reproductive performance. Fermented Chinese chive is known for its antioxidant properties and potential reproductive benefits, but their individual and combined effects on ovarian function remain unclear in post-pubertal mice. In this study, a 21-day oral gavage model in female Kunming mice was used to evaluate the effects of DON (2 mg/kg/day), fermented Chinese chive extract (LEEK; 0.2 mL/day), and their combined exposure (LKDON) on ovarian physiology, oocyte quality, and ovarian transcriptomic responses. The results showed that DON exposure significantly reduced the zygote cleavage rate, increased intracellular reactive oxygen species levels, and disrupted oocyte mitochondrial membrane potential. While histological examination revealed disturbed follicular architecture. Transcriptomic hub gene analysis showed that DON exposure down-regulate the key associated with innate immune responses and motile cilia/axonemal structure, including Rsph4a, Drc1, Zmynd10, Hydin, and Tmem212. In contrast, LEEK alone was associated with immunomodulatory upregulated genes, including Il5, Cd27, and Crp. Interestingly, LKDON and DON comparison revealed upregulation of a motile cilia/axoneme gene network (Dnah5, Dnah11, Tekt1, Zmynd10, Cfap44, and Spag6l), rather than a global reversal of DON-induced changes. Overall, finding suggest that DON disrupts ovarian immune and structural pathways, while fermented Chinese chive provides partial protection by modulating specific biological processes. Further studies are needed to confirm the underlying mechanisms. Full article

Background: Genetic causes of growth failure should be suspected in patients born small for gestational age (SGA) who fail to show postnatal catch-up growth, present with severe short stature (SS), and exhibit a poor or absent response to growth hormone (rhGH) therapy. Mutations in the insulin-like growth factor 1 receptor (IGF1R) gene are associated with impaired growth, intrauterine growth restriction (IUGR), low birth weight and/or length, and postnatal SS. Case Description: A 9-year-old boy, born SGA for birth length, was evaluated for severe SS. Common causes of SS were excluded. At 9 years and 7 months of age, his height was 112.6 cm (−3.99 SDS), weight 18 kg (−3.79 SDS), and BMI 14.2 kg/m² (−1.8 SDS); pubertal development was Tanner stage 1. The target height was 158 cm (−2.62 SDS). Bone age was delayed by approximately one year compared with chronological age. Serum IGF-1 levels were within the upper-normal range for age. GH therapy (0.035 mg/kg/day) was initiated due to the lack of catch-up growth in an SGA subject. After three years of treatment, the height gain was only 0.5 SDS. IGF-1 levels showed a transient treatment-related increase, followed by persistent normalization during ongoing therapy. Next-generation sequencing (NGS) analysis identified novel heterozygous paternal nonsense variant in the IGF1R gene: c.3498C>G (p.Tyr1166Ter). At 12 years of age, impaired fasting glucose and reduced glucose tolerance were detected; consequently, it was decided to discontinue rhGH therapy, also in light of the IGF1R mutation and the lack of height recovery. Conclusions: This case underlines the critical role of genetic testing in the evaluation of patients born SGA. The coexistence of SGA status and an IGF1R gene mutation may provide a clear explanation for both the poor response to rhGH therapy and the increased risk of alterations in glucose metabolism. An extensive narrative review of the literature on growth outcomes and glucose metabolism abnormalities during GH treatment in SGA patients carrying IGF1R variants was also performed. Full article

Puberty is a neuroendocrine process required for sexual maturity; it is regulated by the hypothalamic–hypophysis–gonadal (HHG) axis. Kisspeptin (KISS1) plays a vital role in activating this axis by stimulating the secretion of gonadotropin-releasing hormone (GnRH). Cadmium (Cd) exposure disrupts KISS1 signaling in female rodents; its effects on hypothalamic gene expression during male puberty remain poorly understood. This study investigated the effects of Cd exposure on hypothalamic Kiss1, Kiss1r, and Gnrh1 expression, preputial separation (PS) as a marker of pubertal onset, testosterone levels, Cd concentration, and total antioxidant capacity (TAC) in the serum and hypothalamus of pubertal male Wistar rats. Animals received once a week intraperitoneal injection of CdCl₂ (1 mg/Kg body weight/100 µL) or saline (100 µL) and were euthanized on postnatal day (PND) 35 or 49. Cd exposure reduced serum testosterone levels and TAC. Also, pubertal onset was delayed. At PND 35, Cd decreased hypothalamic Kiss1 expression, whereas at PND 49, it reduced Kiss1r and Gnrh1 expression. These results suggest that Cd alters hypothalamic gene expression, which may contribute to delayed puberty and impaired sexual maturity. Our findings suggest the vulnerability of puberty to exposure to Cd, acting as an endocrine disruptor and neurotoxicant, with alterations for male reproductive maturity. Full article

Tibetan sheep, a dominant livestock species on the Qinghai–Tibet Plateau, is characterized by late sexual maturity and low reproductive efficiency. Although long non-coding RNAs (lncRNAs) are known to play critical regulatory roles in mammalian testicular development and spermatogenesis, their expression dynamics and functions in Tibetan sheep remain poorly understood. In this study, we integrated histological and transcriptomic analyses to profile testicular lncRNAs across three developmental stages: pre-pubertal (3 months), sexually mature (1 year), and adult (3 years). Histological examination showed progressive structural maturation of seminiferous tubules, accompanied by significant increases in testicular weight and serum testosterone levels. RNA sequencing identified 10,857 high-confidence lncRNAs and uncovered extensive reprogramming of the lncRNA transcriptome during sexual maturation, with 7784 lncRNAs differentially expressed between pre-pubertal and post-pubertal stages. Functional enrichment analyses of cis- and antisense-target genes indicated that these lncRNAs were involved in key biological processes, including cell cycle regulation, TGF-β and Hippo signaling pathways, extracellular matrix organization, glycolysis, and apoptosis. Co-expression network analysis further linked upregulated lncRNAs to spermatogenesis-related genes involved in processes such as sperm nuclear condensation (e.g., TNP1) and metabolic support (e.g., PFKP). Our findings demonstrated that lncRNAs coordinate testicular development and spermatogenesis in Tibetan sheep by modulating transcriptional networks, remodeling the cellular microenvironment, and reprogramming energy metabolism. This study provides the first comprehensive atlas of testicular lncRNAs in Tibetan sheep and offers novel insights into the epigenetic regulation of male reproduction in high-altitude mammals. Full article

Reproductive efficiency is a key determinant of sheep productivity, yet Hetian sheep remain limited by relatively low fecundity despite their adaptability to harsh environments. The inhibitor of DNA binding 2 (ID2) gene is known to regulate cell proliferation and differentiation, but its specific role in sheep reproduction is not well understood. This study aimed to characterize the ID2 gene in Hetian sheep and to assess its functional association with ovarian granulosa cells and litter size. The coding sequence of ovine ID2 was cloned and analyzed using bioinformatics tools. Tissue-specific expression patterns were measured by quantitative PCR at different pubertal stages. A total of 157 ewes were genotyped to identify single-nucleotide polymorphisms (SNPs) and their association with litter size. Functional studies were performed by lentiviral overexpression of ID2 in granulosa cells, with effects evaluated using CCK-8 proliferation assays, ELISA for hormone secretion, and RT-qPCR for related gene expression. ID2 was highly expressed in the ovary, particularly during puberty. Four SNPs (g.18202368 A>T, g.18202372 G>A, g.18202431 G>C, g.18202472 G>C) were significantly associated with increased litter size. Overexpression of ID2 promoted granulosa cell proliferation, increased progesterone, decreased estradiol, and altered expression of key genes in the TGF-β/BMP-SMAD signaling pathway. The ID2 gene plays a crucial role in ovarian function and reproductive regulation in Hetian sheep. Its polymorphisms and functional impact on granulosa cells suggest that ID2 is a promising candidate gene for marker-assisted selection to improve reproductive efficiency in sheep. Full article

Multilocus pathogenic variation—when multiple genetic disorders coexist in a single individual—remains rare but is increasingly recognized in the era of genomic medicine. Reporting such cases is essential for improving diagnostic accuracy, refining clinical management, and informing genetic counseling. We describe a pediatric case with a complex phenotype resulting from the coexistence of two distinct genetic diagnoses—cerebrotendinous xanthomatosis (CTX), a rare autosomal recessive lipid storage disorder caused by biallelic mutations in the CYP27A1 gene and Klinefelter syndrome a common sex chromosome aneuploidy occurring in approximately 1 in 600 males, characterized by hypogonadism, gynecomastia, pubertal delay, infertility, micrognathia, and neurodevelopmental challenges—and an additional incidental finding with clinical relevance. The patient was born to consanguineous parents, presented with neurological symptoms, gastrointestinal dysfunction, endocrine abnormalities, and dysmorphic features. Trio-based exome sequencing identified a homozygous pathogenic variant in CYP27A1 consistent with CTX, while conventional G-banded karyotyping revealed a 47,XXY chromosomal pattern, confirming Klinefelter syndrome. Additionally, a heterozygous pathogenic variant in BRCA2 was incidentally detected, associated with hereditary cancer predisposition. The overlapping manifestations of CTX and Klinefelter syndrome produced a non-classical presentation that delayed diagnosis. Although the BRCA2 variant did not contribute to the current phenotype, it has important implications for future cancer surveillance and family risk assessment. This case underscores the importance of combining classical cytogenetic and modern genomic methods to elucidate complex phenotypes, particularly in consanguineous populations, and highlights the need for the multidisciplinary management of patients with multilocus or incidental findings. Full article

Pubertal molting represents a pivotal transition in the life cycle of crustaceans, marking the shift from somatic growth to reproductive development. In mud crabs, mating is known to facilitate this process, yet the molecular mechanisms remain poorly understood. Here, we applied full-length transcriptome sequencing to characterize changes in gene expression and alternative splicing (AS) across post-mating ovarian development. AS analysis revealed extensive transcript diversity, predominantly alternative first exon (AF) and alternative 5′ splice site (A5) events, enriched in genes linked to chromatin remodeling, protein regulation, and metabolism, underscoring AS as a fine-tuning mechanism in ovarian development. Comparative analyses revealed profound molecular reprogramming after mating. In the UM vs. M1 comparison, pathways related to serotonin and catecholamine signaling were enriched, suggesting early neuroendocrine regulation. Serotonin likely promoted, while dopamine inhibited, oocyte maturation, indicating a potential “inhibition–activation” switch. In the UM vs. M3 comparison, pathways associated with oxidative phosphorylation, ATP biosynthesis, and lipid metabolism were upregulated, reflecting heightened energy demands during vitellogenesis. ECM-receptor interaction, HIF-1, and IL-17 signaling pathways further pointed to structural remodeling and tissue regulation. Enhanced antioxidant defenses, including upregulation of SOD2, CAT, GPX4, and GSTO1, highlighted the importance of redox homeostasis. Together, these findings provide the first comprehensive view of transcriptional and splicing dynamics underlying post-mating ovarian maturation in Scylla paramamosain, offering novel insights into the molecular basis of crustacean reproduction. Full article

This investigation examines the function of the mouse Mycn gene in regulating and activating quiescent mammary stem cells, which are vital for mammary gland development. The mammary gland, consisting of luminal and basal cells, progresses through complex developmental stages from embryonic development through puberty, adulthood, pregnancy, lactation, and involution. Quiescent stem cells, existing in a reversible non-proliferative state, are essential for gland maintenance, yet their activation mechanisms remain poorly understood. Mycn, a member of the Myc/MYC oncogene family, is recognized for its roles in embryonic development and cancer, notably aggressive neuroblastoma and triple-negative breast cancer. Through single-cell RNA sequencing (scRNA-seq), CRISPR knockout, and overexpression experiments, this study demonstrates that Mycn is highly enriched in the terminal end buds (TEBs) of the pubertal mammary gland, particularly in basal cells, and is critical for ductal development. Both deletion and overexpression of Mycn diminish the stemness and regenerative capacity of mammary stem cells. Mycn enhances cell proliferation while downregulating quiescent stem cell markers and regulators, including Bcl11b and Tspan8, affecting stem cell maintenance and differentiation. This research clarifies the regulatory role of Bcl11b in controlling Tspan8 expression and demonstrates that Mycn indirectly targets both under normal conditions. Maintaining appropriate levels of Mycn expression is essential for normal development and cancer prevention. These insights contribute to understanding diseases and aggressive cancers, including triple-negative breast cancer (TNBC), and suggest potential therapeutic approaches. Full article

The aim of this study was to determine whether a low dose of zearalenone (ZEN) affects the mRNA expression of the CYP1A1 (P450 cytochrome) and GSTπ1 (glutathione S-transferase) genes in the large intestine of pre-pubertal gilts. Materials: Control (C) group gilts (n = 18) received a placebo. Experimental (E) group gilts (n = 18) were orally administered 40 μg ZEN/kg body weight (BW) each day before morning feeding for 42 days. Three animals from each group were sacrificed each week of the study. Tissue samples were collected from the medial parts of the ascending colon and the descending colon on six dates. Results: Zearalenone concentrations were multiple times higher in the last three weeks of exposure, and ZEN metabolites were not detected. In phase I, CYP1A1 mRNA expression in the ascending colon was suppressed in the final three weeks of exposure, which substantially increased the ZEN concentration in the descending colon. In phase II, ZEN levels were high in the descending colon due to CYP1A1 suppression in the ascending colon. Consequently, the phase II detoxification processes could not take place due to the absence of a substrate. Conclusion: This study demonstrated that low-dose ZEN mycotoxicosis disrupts the expression of the CYP1A1 and GSTπ1 genes, which co-participate in the enzymatic biotransformation of ZEN in both examined sections of the large intestine. The above could have contributed to increased ZEN accumulation in the mucosa of the descending colon in the last three weeks of exposure. Full article

Osteogenesis imperfecta (OI) is a rare bone dysplasia that occurs with a frequency of 1/15,000–20,000 live births. It is characterized by increased susceptibility of bone fractures, skeletal deformities, low stature, and low bone mass. It results in impaired production of type I collagen. About 90% of people with OI have heterozygous mutations in the COL1A1 and COL1A2 genes. Fibroblast growth factor 23 (FGF23) is a protein involved in the regulation of phosphate and 1,25-dihydroxyvitamin D₃ metabolism on a negative feedback basis. FGF23 is secreted by osteocytes in response to increased serum calcitriol and phosphorus. The purpose of this study was to evaluate the concentration of FGF23 among children with osteogenesis imperfecta and the differences in reference values in a healthy population of children and adolescents. Then, this study sought to evaluate how the course of osteogenesis imperfecta, including type of disease, number of bone fractures, and bone mineral density, are related to FGF23 concentration. The study included 47 children aged 3 to 17 years with a diagnosis of osteogenesis imperfecta, confirmed by genetic tests. The patients were hospitalized at the Department from August 2019 to September 2020 and were treated with intravenous infusions of sodium pamidronate. The course of the disease was analyzed, including the number of bone fractures, clinical symptoms, and anthropometric parameters, and bone densitometry was performed by dual X-ray absorptiometry (DXA) in Total Body Less Head (TBLH) and Spine options with Z-score evaluation. FGF23 concentration was determined by the ELISA method. The study was prospective in nature. Results: The mean level of FGF23 in the study group of patients was 645.09 pg/mL and was within the reference values for the developmental age population. There was no significant correlation between FGF23 concentration and anthropometric measurements: body weight (p = 0.267), height (p = 0.429), gender (p = 0.291), or pubertal stage (p = 0.223) in the study group of patients. FGF23 levels were not related to the number of fractures (p = 0.749), the number of sodium pamidronate cycles administered (p = 0.580), bone mineral density parameters (Z-score), the form of osteogenesis imperfecta (p = 0.156), or the genetic test result (p = 0.573). FGF23 levels decrease with age (r = −0.32, p = 0.030) and BMI (r = −0.34, p = 0.020). The level of FGF23 in patients with osteogenesis imperfecta is lower among older children and those having a higher BMI. This index cannot be a diagnostic tool in this group of patients, for no differences were found between the concentrations in patients with osteogenesis imperfecta and the developmental age population. Full article

This overview explores the complex relationship between environmental factors, particularly obesity, and the timing of puberty, with a focus on how hormonal and genetic interactions are influenced by external conditions. Puberty (gonadarche) is characterised by the activation of the hypothalamic–pituitary–gonadal (HPG) axis. The onset and progression of puberty vary significantly among individuals, primarily due to genetic factors, with key genes like kisspeptin 1 (KISS1) and makorin ring finger protein 3 (MKRN3) playing a crucial role. Cohesively, this paper emphasises that environmental factors, particularly obesity and exposure to endocrine-disrupting chemicals (EDCs), have become significant influences on the timing of puberty. Childhood obesity has risen significantly in recent decades and the age of pubertal onset has declined over the same period. Obesity greatly disrupts hormone regulation in pre-pubertal children. Leptin accelerates the onset of puberty in girls but not in boys. The underlying mechanism is proposed to be the increase in Kiss1/GnRH signalling. On the contrary, excess leptin in boys suppresses testosterone production by increasing oestrogen conversion. Low adiponectin in obese girls may contribute to earlier puberty due to a reduced inhibition of Kiss1/GnRH signalling. Low adiponectin in boys is linked to delayed puberty due to its role in maintaining insulin sensitivity and testosterone production. Hyperinsulinemia influences pubertal timing through central and peripheral mechanisms. Insulin acting synergistically with leptin promotes the earlier onset of puberty in girls but not in boys. The effects of exposure to certain EDCs—mostly obesogenic chemicals that mimic the action of natural hormones—on the timing of puberty remain unclear; hence, further research on this topic is needed. Addressing and preventing obesity in children could potentially mitigate these alterations in pubertal timing. Full article

Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in pre-pubertal cynomolgus macaques, a commonly used surrogate species to humans. Methods: A transcriptomic profile using RNA sequencing was generated for the temporal lobe, ventral midbrain, and cerebellum of three female and three male cynomolgus macaques previously treated with an adeno-associated virus vector mix. Statistical analyses to determine differentially expressed protein-coding genes in all three lobes were conducted using DeSeq2 with a false-discovery-rate-corrected p-value of 0.05. Results: We identified target genes in the temporal lobe, ventral midbrain, and cerebellum with functions in translation, immunity, behavior, and neurological disorders that exhibited statistically significant sexually divergent expression. Conclusions: We provide potential mechanistic insights into the epidemiological differences observed between the sexes with regard to mental health and infectious diseases, such as COVID-19. Our results provide pre-pubertal information on sexual differences in non-human primate brain transcriptomics and may provide insight into health disparities between the biological sexes in humans. Full article

Lin28b and let-7 miRNA regulate mammalian pubertal initiation and Gonadotropin-releasing hormone (GnRH) production. However, it remains unclear which signaling pathways Lin28b regulates to modulate GnRH production. In this study, the mRNA expression levels of Lin28b and let-7 in the pubertal and juvenile goat hypothalamus and pituitary gland were detected, and Lin28b expression in the pubertal hypothalamus decreased significantly compared with that in juvenile tissues. It was predicted that Lin28b might inhibit GnRH1 expression, which was verified in the GnRH-producing cell model GT1-7 cells. Lin28b inhibited GnRH1 expression and promoted Kiss1/Gpr54 signaling. The pyruvate content and the expression of Hif1a and Hk2, which were related to glycolysis, were also promoted by Lin28b overexpression. Additionally, 77 differentially expressed miRNAs (DEMIs) in Lin28b-overexpressed GT1-7 cells were identified. Bioinformatics analysis and mRNA expression of the target genes of DEMIs revealed that the MAPK and PI3K-AKT-mTOR signaling pathways were key pathways that involved the regulatory effect of Lin28b on GnRH. In GT1-7 cells, GnRH1 expression was suppressed by blocking mTOR signaling with rapamycin, which was rescued by Lin28b overexpression. These results indicate that Lin28b-let-7 regulates GnRH1 expression through several pathways, including the Kiss1/Gpr54, MAPK, and mTOR signaling pathways, which are all related to glucose metabolism and provide new insights into the molecular mechanism of the regulatory role of Lin28b on GnRH production. Full article