Search Results (332)

Hypoxia–ischemia (HI)-related brain injury impacts millions of neonates worldwide. Male neonates are two times more susceptible to developing HI. We have previously reported that the administration of the neurotrophin receptor tyrosine kinase B (TrkB) agonist 7,8-dihydroxyflavone (DHF) following neonatal HI increases hippocampal TrkB phosphorylation and improves hippocampal-dependent learning and memory in early adult life only in females. We hypothesize that sex differences in HI outcomes are due to alterations in neonatal hippocampal steroid content, mainly the neural testosterone. At postnatal day 9, C57BL/6J mice underwent sham and Vannucci’s HI surgeries and were treated either with DHF or vehicle control. Hippocampi and plasma were collected on days 1 and 3 post-HI and liquid chromatography tandem mass spectrometry was used to determine the testosterone (T), estradiol (E₂), progesterone (P₄), and corticosterone (CORT) contents in these samples. All hippocampal steroid contents were at least 10-fold higher than in plasma, suggesting neural synthesis. Males had higher hippocampal T content than females at 3 days post-HI. Treatment with DHF reduced T in the female hippocampi at 3 days post-HI, but not in males. These findings suggest that the neuroprotective effect of DHF in females may be mediated, at least in part, through the reduction in hippocampal T following HI. Full article

Thamnaconus septentrionalis is an emerging commercially important aquaculture species in China, distributed extensively in the Indo-West Pacific Ocean. Recently, because of the seriously declining population and considerable economic potential of this aquaculture fish, increasing attention has been paid to the conservation and development of T. septentrionalis. Artificial fish breeding is essential and has become progressively implemented on local farms in China, which benefits the protection of T. septentrionalis resources and facilitates the development of its fishery industry. Previous studies have demonstrated that temperature could significantly influence ovary development in T. septentrionalis. However, the potential molecular mechanisms underlying the influence of temperature on testis development in T. septentrionalis have been scarcely studied. Thus, this study comprehensively explores the effects of temperature on testis development in T. septentrionalis using histological observation and transcriptomic techniques. Histological and transmission electron microscopy analyses indicated that T. septentrionalis testes, undergoing a rise in temperature, developed from phase III to IV. Transcriptomic analysis identified 315 differentially expressed genes, including 200 upregulated and 115 downregulated genes. Moreover, rising temperatures may enhance testis development by regulating steroid hormone biosynthesis, cellular senescence, and nucleotide metabolism. The upregulation of four genes (hsd11b2, cyp11b, cyp11a, and hsd17b3) involved in the steroid hormone biosynthesis process may significantly contribute to the increased level of testosterone and 11-keto-testosterone. This study is the first to elucidate the potential molecular mechanism involved in T. septentrionalis testis development induced by temperature, offering valuable and novel insights for its artificial breeding and fishery resources conservation. Full article

Despite the evidence from experimental studies that endogenous hormones have sex-related effects on action potential duration, the relationship between gonadal steroids and ventricular repolarization in acute myocardial infarction (AMI) is not clear. We tested the hypothesis that endogenous 17β-estradiol (E2) and 17β-estradiol-to-testosterone ratio (E2/T) are associated with inflammation, influencing the occurrence of early ventricular arrhythmia (VA) in AMI. Electrocardiographic (ECG) repolarization indices, including resting heart rate (HR), corrected QT (QTc) interval, QTc minimum (QTcmin), QTc maximum (QTcmax), and QTc dispersion (QTcd), along with E2, total T, and the ratio of E2 to T (E2/T), were measured and analyzed after percutaneous coronary intervention in 86 patients (36 women, 41.9%). In a non-specific sex analysis, the incidence of early VA in the course of AMI was determined by the ejection fraction of the left ventricle (OR 0.876, p = 0.054), and by the peak levels of plasma C-reactive protein (OR 1.026, p = 0.077). Endogenous plasma 17β-estradiol tended to be higher in cases with early ventricular arrhythmia (124.5 ± 79 vs. 181 ± 192.8, p = 0.089). 17β-estradiol levels were significantly predicted by C-reactive protein (OR 1.050, p = 0.042). This study found that reduced systolic function of the left ventricle and higher peak CRP levels are associated with endogenous plasma 17β-estradiol in the acute phase of MI, and predicted the risk of early in-hospital ventricular arrhythmia. Full article

Testosterone (T) produced by Leydig cells (LCs) is essential for male reproduction; yet, the regulatory mechanisms underlying steroidogenesis remain incompletely understood. Here, we investigated the role of cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) in Leydig cell development and steroidogenesis, based on its identification by immunoprecipitation-mass spectrometry (IP-MS) as a protein associated with steroidogenesis and cholesterol metabolism in mouse testicular tissue. Using human samples, we found that CDK5RAP3 expression was significantly reduced in Leydig cells from patients with spermatogenic failure (T < 10.4 nmol/L). Notably, CDK5RAP3 expression increased during mouse postnatal Leydig cell maturation and regeneration in an ethane dimethanesulfonate (EDS)-induced rat model. Functional analyses in primary LCs and MLTC-1 cells showed that hCG stimulation triggered CDK5RAP3 nuclear translocation without altering its overall expression, while CDK5RAP3 knockdown markedly impaired hCG-induced testosterone production and reduced the expression of the steroidogenic regulator steroidogenic acute regulatory (STAR) protein, as well as key steroidgenic enzymes, including cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 17a-hydroxylase (CYP17A1), and 3β-hydroxysteroid dehydrogenase (HSD3B). Conversely, CDK5RAP3 overexpression enhanced testosterone production in the absence of hCG. In vivo, AAV2/9-mediated CDK5RAP3 silencing in adult mouse testes resulted in a significant reduction in serum testosterone levels compared with controls (3.60 ± 0.38 ng/mL vs. 1.83 ± 0.37 ng/mL). Mechanistically, CDK5RAP3 interacted with SMAD4 and CEBPB, and BMP pathway inhibition by Noggin rescued the testosterone deficit caused by CDK5RAP3 loss. Together, these findings identify CDK5RAP3 as an essential regulator of Leydig cell steroidogenesis and provide insight into its potential relevance to male infertility associated with low testosterone. Full article

Testosterone, an androgenic steroid hormone, regulates primary sexual characteristics and influences mood, cognition, social behavior, and sexual function. Deficiency, caused by factors such as aging and genetics, is linked to multiple disease conditions. However, current testosterone therapies are limited by extensive metabolism, poor solubility, and undesirable side effects. To address these limitations, we synthesized a four-armed star PEG-OH-linked testosterone (PEG-T). The in vitro release of testosterone from PEG-T was evaluated in buffer (pH 7.4) and mouse plasma. PEG-T was stable in the buffer, but released testosterone in plasma via esterase-mediated hydrolysis. Pharmacokinetics of testosterone and PEG-T were compared following intraperitoneal (IP) and subcutaneous (SC) administration. Following IP dosing, PEG-T exhibited a ~6-fold improvement in half-life compared to testosterone (1.18 h vs. 0.21 h), and a 54-fold increase in exposure (AUC_0-t = 36.0 μM·h vs. 0.67 μM·h) at equimolar doses; furthermore, following SC dosing, PEG-T showed a 4-fold improvement in both half-life (3.57 h vs. 0.91 h) and plasma exposure (11.5 μM·h vs. 3.1 μM·h). Additionally, PEG-T showed lower liver and kidney to plasma ratios, which could potentially result in reduced hepatotoxicity and nephrotoxicity. Overall, PEG-T provides sustained release pharmacokinetics, representing a promising candidate for safer testosterone replacement therapy. Full article

Taenia crassiceps is a cestode capable of causing severe and atypical cysticercosis in accidental intermediate hosts, including domestic dogs. Here we report a fatal disseminated T. crassiceps infection (cystiscercosis) in a 4-year-old castrated male German Shepherd from Poland that had been undergoing long-term prednisone therapy for Addison’s disease. The dog developed multiple soft subcutaneous nodules containing numerous asexually proliferating cysticerci. Necropsy revealed extensive dissemination of larvae throughout the subcutis and the thoracic and abdominal cavities, accompanied by serosanguineous effusions, necrosis, and chronic inflammatory lesions. Histological examination demonstrated cestode larvae with a scolex bearing two rows of hooks, consistent with T. crassiceps. Immunosuppression and endocrine alterations, including chronic glucocorticoid treatment and low levels of testosterone, likely promoted rapid asexual proliferation of larvae. A literature review shows that although dogs are definitive hosts of T. crassiceps, immunosuppressed individuals may also serve as accidental intermediate hosts. Early cytological evaluation of subcutaneous nodules may facilitate faster diagnosis and treatment decisions. Given the zoonotic potential of T. crassiceps and the increasing number of European cases, this parasitic infection should be considered in the differential diagnosis of subcutaneous nodules in immunosuppressed dogs. The presented case underscores its epidemiological relevance within the One Health framework. Full article

Background/Objectives: Silver nanoparticles (AgNPs), used in industry and medicine, can have a negative impact on the human organism, particularly on the reproductive system, while polyphenolic supplementation may reduce oxidative stress (OS) and enhance male reproductive potential. The aim of this study was to investigate the effects of anthocyanin-rich blackcurrant pomace (BC) on sex steroid hormone metabolism and the OS indicator in the testes of rats following exposure to AgNPs. Methods: Adult rats were fed with a control feed (CTR) or diet supplemented with a 2% BC (BC group). The rats from AgNano and AgNano+BC groups were treated with 20 nm AgNPs (30 mg/kg/day for 28 days by gavage). Results: The plasma testosterone (T) and plasma dihydrotestosterone (DHT) concentrations were decreased in all experimental groups compared to the control (CTR) animals. The co-treatment of animals with AgNPs and BC resulted in decreased oestrogen receptor (ESR2) levels in the testes as compared to rats fed with a diet with BC alone, and the up-regulation of mRNA level of genes involved in T synthesis and metabolism (StAr, Cyp11a1, Hsd17b3, Hsd3b3, Cyp19a1, and Srd5a1), and steroid hormone signalling (AR, ESR1, and ESR2) compared to the Ctr group. The addition of BC to the diet of rats treated with AgNPs resulted in decreased protein carbonyls in the testes as compared to AgNPs-treated animals. Conclusions: The study demonstrated that relatively low AgNPs administration to rats was associated with increased oxidative stress in the gonads. Incorporating BC into the animals’ feed mitigated AgNPs-induced oxidative stress and stimulated the expression of genes involved in steroid synthesis and metabolism in testes. The bioactive compounds in blackcurrant pomace have plausible mechanisms to influence reproductive health. Full article

This study evaluated the effect of dietary supplementation with biochar and Tribulus terrestris (TT) on oxidative stress and metabolic parameters in New Zealand White rabbits. A total of 80 weaned rabbits (35 days of age) were assigned to four groups (20 each): a control group (C) and three experimental groups supplemented with 0.25% biochar (E1), 0.25% biochar and 0.1% Tribulus terrestris (E2), or 0.1% Tribulus terrestris (E3). The feeding experiment lasted 78 days following a 7-day adaptation period. Hematological, biochemical, and redox parameters, including malondialdehyde (MDA), glutathione (GSH), total reducing capacity (FRAP), immunoglobulin G (IgG), and testosterone levels, were assessed and analyzed using one-way analysis of variance (ANOVA). Rabbits from group E1 exhibited the highest FRAP values (8.16 µmol/L; p < 0.05), whereas MDA concentrations were significantly elevated in groups E1 and C (2.02 and 1.83 µmol/L; p < 0.05), indicating increased lipid peroxidation. Groups E2 and E3 showed lower MDA levels (1.38 and 1.59 µmol/L; p < 0.05) and higher IgG concentrations (44.72 and 37.82 ng/mL; p < 0.05) compared to the control, suggesting improved antioxidant defense and immune status. GSH levels were significantly higher in groups E1 and E2 (6.34 and 6.79 µmol/L; p < 0.05). No adverse changes were observed in basic hematological and biochemical parameters. The results indicate that dietary supplementation with biochar and T. terrestris is safe and can beneficially modulate redox balance and immune response in rabbits, confirming their potential as natural feed additives in sustainable rabbit production. Full article

In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. These light-driven pathways modulate endocrine activity, playing a key role in muscle development. This review explores how monochromatic light-emitting diode (LED) illumination, particularly green and blue wavelengths, affects the somatotropic axis (growth hormone-releasing hormone [GHRH]-growth hormone [GH]-insulin-like growth factor 1 [IGF-1]), the gonadal axis (gonadotropin-releasing hormone [GnRH]-luteinizing hormone [LH]/follicle-stimulating hormone [FSH]-sex steroids [testosterone, estrogen, progesterone]), the thyroid axis (thyrotropin-releasing hormone [TRH]-thyroid-stimulating hormone [TSH]-thyroxine [T₄]/triiodothyronine [T₃]), and the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing hormone [CRH]-adrenocorticotropic hormone [ACTH]-corticosterone). Green light enhances early-stage muscle growth via GHRH and IGF-1 upregulation, while blue light supports later myogenic activity and oxidative balance. Light schedules also influence melatonin dynamics, which in turn modulate endocrine axis responsiveness to photic cues. Furthermore, variations in photoperiod and exposure to artificial lights at night (ALAN) affect thyroid activity and HPA axis reactivity, influencing metabolism, thermoregulation, and stress resilience. Together, ocular and intracranial photoreception form a complex network that links environmental light to hormonal regulation and muscle growth. These insights support the strategic use of LED lighting to optimize broiler performance and welfare. Full article

Background: Long QT syndrome (LQTS) is characterized by delayed myocardial repolarization, predisposing to malignant arrhythmias such as torsades de pointes, ventricular fibrillation, and cardiac arrest. Recent reports suggest that acquired LQTS (aLQTS) may represent an early manifestation of hypopituitarism, potentially contributing to its increased cardiovascular mortality, although evidence remains limited to 16 published case reports. Objective: The objective was to investigate the relationship between hypopituitarism and corrected QT (QTc) interval. Methods: We retrospectively analyzed data from 185 patients (121 males) with hypothalamic–pituitary disorders who underwent a 12-lead electrocardiogram between April 2023 and September 2024. Clinical characteristics, hormone replacement therapy, and same-day laboratory parameters (electrolytes, fT3, fT4, IGF-I, testosterone) were recorded. QTc was calculated using Bazett’s formula. Multivariate logistic regression identified predictors of QTc prolongation. Results: Age (OR 1.07–1.09, p = 0.02) was a significant predictor in 5 of 8 models. The presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts was also associated with QTc prolongation (OR 8.35–17.73, p < 0.05 and p = 0.03). Potassium (OR 0.14–0.17, p = 0.09) and albumin-corrected calcium levels (OR 0.0003, p = 0.06) showed consistent, though borderline, associations. Conclusions: Age and the presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts are the main predictors of QTc duration in patients with hypothalamic–pituitary disease. Electrolyte imbalances—particularly low potassium and albumin-corrected calcium—may further contribute. The influence of specific pituitary deficiencies remains uncertain, likely due to adequate replacement therapy in most patients. Full article

Psychological “priming” strategies such as music, self-talk, imagery, and audience effects are commonly used by athletes, yet their acute influence on resistance training performance and underlying endocrine responses is unclear. We conducted three crossover studies in collegiate adults (n = 64) examining self-selected music (SSM), motivational self-talk with imagery (MSTI) or without (MST), and observation either in-person (OE) or via social media (SM) compared with control (CON). Performance tests included a 3-repetition maximum (3RM) back squat, four sets of a 4RM bench press, and a 65% 1RM back squat to failure. Salivary testosterone (T) and cortisol (C) concentrations were assessed to explore potential mechanisms. Across studies, no condition yielded statistically significant differences versus CON (p > 0.05); however, small-to-moderate effect sizes suggested practically relevant improvements. For example, 3RM back squat load increased under SSM (g = 0.26) and MSTI (g = 0.22), while SM observation improved repetitions to failure (g = 0.33) and produced a moderate rise in T (g = 0.79). Several priming strategies also favourably altered the T:C ratio. These findings suggest that although group-level changes were subtle, individualized responses may allow athletes to benefit from simple, free interventions that could accumulate into meaningful performance gains when applied repeatedly in training. Future work with larger samples and long-term training designs is warranted to confirm these effects and whether changes in T and C are modulating the priming response. Full article

Objectives: Bisphenol A (BPA), a prototypical environmental endocrine-disrupting chemical (EDC), is ubiquitously present in environmental matrices and biological fluids. Dietary ingestion and inhalation exposure to BPA can induce testicular oxidative stress and apoptosis. This study aimed to investigate the protective effects and underlying mechanisms of Pfaffia glomerata (Pg), a perennial herb of the Amaranthaceae family, against BPA-induced reproductive system injury. Methods: Potential targets and molecular mechanisms were predicted through network pharmacology. Physiological indicators, histopathological changes, serum biochemical parameters, and Western blot analysis were used to systematically evaluate the ameliorative effects of Pg and elucidate its mechanisms. Results: Our network pharmacology analysis identified core targets of Pg in attenuating reproductive system injury, including PTPN11, PIK3CA, JAK2, PIK3R1, PDGFRB, and others. GO enrichment and KEGG pathway analysis indicated that these key targets primarily regulate steroid metabolism, enhance antioxidant capacity, and modulate signaling pathways such as PI3K-AKT, Fc epsilon RI, and cAMP. In vivo studies demonstrated that all Pg dose groups showed significant improvement in BPA-induced histopathological injury to testicular tissues. BPA exposure increased serum levels of follicle-stimulating hormone (FSH) while decreasing testosterone (T), estradiol (E2), and progesterone (PROG) levels. Furthermore, BPA elevated serum levels of the testicular marker enzymes acid phosphatase (ACP) and lactate dehydrogenase (LDH) but reduced alkaline phosphatase (ALP) levels; all these effects were significantly reversed with Pg treatment. Western blot results showed that compared with the model group, high-dose Pg significantly upregulated the expression of phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and Bcl-2, while downregulating Cleaved Caspase-3 and Bax. Conclusions: Our findings indicate that Pg may attenuate BPA-induced reproductive system injury by activating the PI3K/AKT signaling pathway, upregulating the anti-apoptotic protein Bcl-2, and inhibiting the activation of the apoptotic effector Caspase-3. The study provides a new theoretical basis for the development of novel natural drugs or health products. Full article

Several major cancer types exhibit significant sex dimorphism in incidence and survival. Whether and how sex as a biological factor impacts tumorigenesis, progression, and survival warrants full investigation, as such knowledge may lead to novel, precise prevention and treatment strategies. We reviewed epidemiological and molecular data on sex differences in cancers of the esophagus, bladder, head and neck, lung, liver, kidney, stomach, and skin melanoma, as well as the potential role of androgens and androgen receptor (AR) activity in these cancers. The potential molecular mechanisms are briefly discussed. Elevated testosterone (T) levels seemed to be associated with increased liver cancer and cutaneous melanoma incidences, and with reduced esophageal cancer risk. AR activity does not always correlate with T levels in tumorigenesis and progression. Higher AR expressions are associated with poorer survival in ESCC, whereas the role of AR in the survival of HNSCC and melanoma patients is inconsistent. The molecular impact of AR in liver cancer, kidney cancer, melanoma, and lung cancer is controversial. However, AR is likely to promote tumor growth and/or progression in esophagus, bladder, head and neck, and stomach cancers, and thus is associated with poor survival. Patients diagnosed with a tumor in this latter group could potentially benefit from therapeutic approaches targeting AR. Overall, the research on sex hormone androgens and AR in these cancers is limited. Further research is needed to determine a possible U-shaped relationship of T with cancer risk, and to decipher the role of testosterone and AR in some of these tumors to facilitate our understanding of sex dimorphism and to explore novel T/AR-based treatment options. Full article

Bone mineral density (BMD) is a key indicator of skeletal health in boars that influences their reproductive performance. Systematic research on the relationship between BMD and semen quality in adult boars of different breeds and ages is scarce. This study used quantitative ultrasound (QUS) technology to measure BMD in 492 adult and 208 replacement boars. The boars were divided into four equal groups based on descending BMD rankings to analyze correlations with semen quality. Simultaneously, a 25-hydroxyvitamin D₃ (25-OH-D₃) intervention trial was conducted on 150 adult Duroc boars. A control group and four dose groups (50 μg, 125 μg, 200 μg, and 250 μg) were established. After 90 days, the boars’ semen quality, reproductive hormone levels, and bone metabolism indicators were evaluated. The results showed no significant differences in BMD between adult and replacement boars. However, adult Landrace exhibited significantly higher BMD than Duroc and Yorkshire (p < 0.01). Within the BMD groups, Group D boars had significantly higher rates of sperm abnormality than Groups A and B (p < 0.01), and this trend was consistent across breeds. The 25-OH-D₃ intervention results indicated that the 250 μg dosage produced the optimal effect. In this group, boar semen motility significantly improved while sperm abnormality rates significantly decreased. Concurrently, levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), serum osteocalcin (OC), and BMD all increased to some degree. In summary, boar BMD is significantly influenced by breed and age and is closely correlated with the rate of sperm abnormality rate. Supplementing with 250 μg of 25-OH-D₃ effectively enhances reproductive hormone secretion, improves semen quality, and promotes bone formation. This demonstrates its potential value in breeding and nutritional regulation applications. Full article

Sea cucumber ovum are high-value compounds that remain after the processing of sea cucumbers, and their optimal utilization has long posed a challenge. In this research, we systematically examined the therapeutic effects of sea cucumber ovum hydrolysate (SCH) on premature ovarian failure (POF) and its underlying mechanism. We utilized a model of ICR mice induced with 100 mg/kg cyclophosphamide (CP) to evaluate the therapeutic influence of SCH on ovarian performance. The ovarian and uterine indices were significantly decreased in the POF group compared to the control group; however, these trends were notably reversed following SCH intervention. The therapeutic effects of SCH were positively reflected by the alterations induced by CP in levels of estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Regarding oxidative stress, SCH was found to enhance superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) levels, while also alleviating apoptosis in ovarian granulosa cells. Metabolomics analysis revealed hypoxanthine, mannitol, neocnidilide, tryptophan, palmitoleic acid, and protoporphyrinogen IX as potential biomarkers. In conclusion, SCH effectively improves POF induced by CP, thereby reinforcing the potential application of SCH in the domain of functional foods. Full article