Search Results (505)

Once dismissed as “junk”, transposable elements (TEs) have recently gained recognition for their regulatory roles, notably in the brain and during development. The brain is hormone-responsive and the hippocampus in particular is sensitive to circulating gonadal hormones. While transcriptionally active, TE function remains poorly understood, especially in the brain. We and other researchers have shown that one particular TE RNA, B2 SINE ncRNA, is a regulator in the rodent hippocampus, especially after a psychologically stressful event like acute restraint stress. However, it is unknown if B2 SINE ncRNA is necessary for the proper development of hippocampal neurons, and, furthermore, if there are sex differences in this development. This work investigates the differences in the expression of B2 SINE RNA across sexes and its role in the development of primary hippocampal neurons. We utilized pooled locked nucleic acid (LNA) GapmeRs to knock down the expression of B2 SINE RNA, and we treated primary hippocampal neurons with dihydrotestosterone (DHT) to test if there is a difference in dendritic complexity. We used Sholl analysis to quantify branching, number of tips, and Sholl mean. We found a sex difference in both B2 SINE, higher in males compared to females, and ß-actin, lower in males compared to females. Additionally, knocking down B2 SINE RNA results in a reduction in dendritic complexity in male but not in female neurons. Taken together, this work suggests that B2 SINE RNA is expressed differentially and that it plays an important role in the proper development of hippocampal neurons in a sex-dependent manner. Our findings support the identification of a sex-specific biomarker that may enable individualized treatment of conditions influenced by sex. This is the first evidence of the role B2 SINE RNA may play in the regulation of the development of neuronal dendritic structure and the first to show differential regulation by sex. Full article

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global population, poses a significant yet underappreciated threat to reproductive health in both sexes. Although this parasite has long been linked to birth defects caused by infection during pregnancy, new research shows that it also reduces fertility in both sexes through different but related mechanisms. This review synthesizes knowledge on T. gondii-induced reproductive pathology across females and males, examining shared mechanistic themes while respecting tissue-specific differences, and evaluates emerging therapeutic strategies. In females, the parasite establishes persistent uterine reservoirs, triggers decidual immune dysregulation characterized by NK cell cytotoxicity, M1 macrophage polarization, Treg apoptosis, and inflammasome-mediated pyroptosis, while disrupting estrogen and progesterone signaling through both host receptor modulation and intrinsic parasite steroidogenic enzymes (TgCYP450mt, TgMAPR, Tg-HSD). In males, T. gondii breaches the blood–testis barrier, induces germ cell and Leydig cell apoptosis via ER stress and caspase pathways, impairs sperm quality parameters across acute and chronic infection, and disrupts the hypothalamic–pituitary–gonadal axis. Conserved molecular mechanisms—including NLRP3 inflammasome activation, PERK/eIF2α/ATF4/CHOP-mediated ER stress, and oxidative stress—operate in both reproductive tissues. The parasite’s intrinsic steroidogenic capability and bidirectional hormonal manipulation represent a paradigm shift in understanding host–parasite interactions. Conventional antiparasitics face limitations due to poor reproductive sanctuary penetration. Immunomodulatory approaches targeting Trem2, Tim-3, and the NLRP3 inflammasome show promise, along with natural products including Inonotus obliquus polysaccharide and ginseng polysaccharide. Nanomedicine platforms and mRNA vaccine candidates offer new directions for overcoming tissue barrier limitations. Toxoplasma gondii represents a fundamental threat to fertility and pregnancy outcomes rather than merely a risk for congenital infection. Integrated therapeutic strategies addressing direct parasitism, immunopathology, and endocrine disruption are needed. Longitudinal cohort studies, strain-specific mechanistic comparisons, and clinical trials of immunomodulatory adjuncts are urgently required. Full article

Serotoninomics, a nascent emerging discipline within the field of omics, provides a transdisciplinary framework for understanding reproductive toxicology via serotonergic signalling. This research investigates the neuroendocrine effects of permethrin, a commonly used pyrethroid insecticide often considered to pose a low risk to humans, and positions it as a model compound for evaluating reproductive susceptibility beyond conventional endocrine endpoints. It is hypothesized that serotonin, traditionally examined in neuropsychiatric contexts, plays an essential role in gonadal function, hormonal regulation, and emotional resilience. Although permethrins are generally regarded as safe, acute exposure may subtly interfere with serotonergic pathways, potentially resulting in molecular, biochemical, behavioural, and reproductive alterations. These effects could extend beyond immediate exposure, including during gestation, considering permethrins’ ability to cross the placental barrier and influence foetal development. By synthesizing evidence across molecular, organismal, and environmental domains, we advocate for a serotonergic approach to facilitate a more comprehensive assessment of risk and resilience. We emphasize the importance of fostering a transdisciplinary dialogue to redefine reproductive health through the perspectives of serotonergic vulnerability and systemic resilience. Full article

Monosex all-male culture of the giant freshwater prawn (Macrobrachium rosenbergii) maximizes aquaculture yield due to a male growth advantage, but direct hormonal treatment of grow-out populations poses significant food safety risks. This study evaluated the efficacy of dietary 17β-estradiol (E2) in inducing functional neo-females from a fully all-male postlarval population to support an indirect monosex seed production strategy. All-male postlarvae were fed diets supplemented with E2 at concentrations of 0, 50, 100, 150, and 200 mg/kg for 36 days, followed by a 150-day hormone-free post-treatment period to assess growth performance, feminization rates, and gonadal histology. E2 administration successfully induced feminization across all treatments, reaching a peak rate of 35.5% at 150 mg/kg, whereas the control group remained entirely male. During the 36-day treatment period, E2 supplementation transiently enhanced specific growth and survival rates but concurrently reduced feed conversion ratios. Notably, these physiological differences disappeared completely over the 150-day post-treatment phase. Histological assessments confirmed that E2-induced neo-females exhibited normal oogenesis, with gonadosomatic index (GSI) values and oocyte diameters similar to those of wild-caught females. This establishes a definitive, physiologically safe, and non-surgical protocol for producing the neo-female broodstock necessary to sustain high-yield commercial monosex populations. Full article

Epilepsy is associated with impaired reproductive function and testicular pathologies. Intermittent fasting (IF) is a nonpharmacological metabolic intervention with anti-inflammatory and antioxidant effects. This study investigated the protective effects of IF on testicular damage in a genetic absence epilepsy rat model (GAERS), focusing on histomorphology, oxidative stress parameters, and hormonal profiles. Testicular tissues from Wistar control (WC), Wistar + IF (WIF), GAERS control (GC), and GAERS + IF (GIF) groups (total n = 20; 5 rats per group) were evaluated using hematoxylin and eosin and Periodic Acid–Schiff staining. Apoptosis and spermatogenic cell integrity were assessed using caspase-3, P-element-induced wimpy testis (PIWI), and Deleted in Azoospermia-Like (DAZL) immunohistochemistry. Johnsen’s score, seminiferous tubule diameter, and epithelial thickness were quantified. Oxidative stress markers, including catalase, malondialdehyde, glutathione, myeloperoxidase, and superoxide dismutase, were measured using spectrophotometric methods, and serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using ELISA kits. The GC group showed significantly reduced Johnsen scores, tubular diameters, and epithelial thickness, along with disrupted basement membrane integrity and increased caspase-3 immunoreactivity. IF significantly improved histological parameters, restored basement membrane integrity, reduced apoptosis, and increased PIWI and DAZL expression in the GIF group. IF also ameliorated oxidative stress and elevated reproductive hormone levels, indicating positive modulation of the hypothalamic–pituitary–gonadal axis. In conclusion, IF reduces oxidative stress and preserves seminiferous tubules and hormonal function in genetic absence epilepsy, highlighting its potential as a supportive nonpharmacological approach to protect male reproductive health. Full article

Elevated oxidative stress (OS) is a primary driver of ocular neurodegeneration, worsening with age-related declines in gonadal hormones. While the loss of endogenous 17β-estradiol (E2) is a recognized risk factor for retinal degeneration in females, the impact of testosterone depletion in males remains poorly understood. To address this knowledge gap, we employed mass spectrometry-based proteomics and bioinformatic pipelines to characterize retinal protein shifts triggered by orchiectomy (ORX) in the Brown Norway rat. Proteins from ORX and intact retinas were analyzed via a discovery-driven approach using nanoflow liquid chromatography–tandem mass spectrometry with data-independent acquisition. Ingenuity Pathway Analysis^® of differentially expressed proteins (DEPs) revealed nearly 300 significantly regulated canonical pathways, many associated with OS, free radical detoxification, mitochondrial dysfunction and ophthalmic disease. A selected panel of DEPs was verified by protein-targeted data extraction. Notably, pathway analysis revealed the prominence of estrogen receptor signaling over androgen receptor signaling in the retina, despite the loss of male sex hormones following ORX. These findings indicate that E2-mediated pathways play a more significant role in male retinal protection than previously recognized. Our study provides the first proteomics-based evidence of the male rat retina’s heightened susceptibility to ORX-associated OS, identifying potential targets for treating sex hormone deprivation-associated retinal neurodegeneration. Full article

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone–mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies. Full article

Prosocial risk-taking is defined as engagement in altruistic behaviors that may have personal costs. Emerging research indicates that testosterone—a gonadal steroid hormone—is linked to behaviors aimed at promoting one’s social status. In line with these findings, we hypothesized that testosterone levels would be associated positively with prosocial risk-taking. Additionally, according to the dual-hormone hypothesis, this relationship may be moderated by cortisol. To examine these hypotheses, we administered an adapted version of the probabilistic gambling task, which included a prosocial condition. In the original task, participants were the beneficiaries of their choices; under the prosocial condition, the benefits were directed to charitable organizations. Our results revealed that, consistent with previous findings, the endogenous testosterone level was associated positively with risk-taking for personal gain. Notably, we also observed an association between the endogenous testosterone level and prosocial risk-taking. These relationships were not moderated by cortisol, meaning that the dual-hormone hypothesis was not supported. Instead, elevated cortisol independently suppressed prosocial risk-taking. Collectively, these results demonstrate that basal testosterone and cortisol levels play different roles in the modulation of prosocial risk-taking behavior. Full article

This research aimed to examine the effects of different dietary levels of nano-selenium (NSE) on the reproductive performance, gonad hormones, histopathology, growth performance, feed utilization, and body indices in adult Nile tilapia, Oreochromis niloticus, broodstock for 90 days. The initial weights of the fish were 278.6 ± 5.5 (males) and 178.4 ± 1.6 (females). They were distributed randomly to 15 tanks with 20 fish in each tank (15 females and 5 males, sex ratio 3:1), with each treatment conducted with three replicates. The contents of NSE in five isocaloric and isonitrogenous practical feeds were 0 mg/kg (control), 1 mg/kg (T1), 2 mg/kg (T2), 3 mg/kg (T3), and 4 mg/kg (T4). Results show that the final weight (FW), weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) were significantly better in T2 and T1, followed by the control, in comparison with others. On the other hand, growth efficiency was decreased in T3 and T4 of both males and females. Referring to body indices and reproductive performance, females were higher than males in the hepatosomatic index (HSI), where the lowest treatment was the control and T4 for both males and females. Female Nile tilapia brood fish given NSE improved reproductive performance indicators (egg number, total egg, and fry number) when compared with the control. With increasing levels of NSE in the feed, the levels of testosterone and progesterone hormones were increased. The highest values for testosterone were in T4, followed by T3, then T2, T1, and the control. The same trend was observed across the progesterone treatments. Additionally, the results of histopathological examination indicate differences in tissues between different treatments as a result of the addition of NSE. These results indicate that NSE supplementation at low levels could lead to improved growth and reproductive efficiency of Nile tilapia. Full article

Modern genetic selection for high productivity has created a physiological conflict in ruminants, where the metabolic demands of lactation compete directly with the energy requirements of reproduction. This review provides a mechanistic synthesis of how key nutritional factors modulate the endocrine and cellular pathways governing reproductive success in cattle and sheep. Negative energy balance (NEB), characteristic of the early postpartum period, suppresses the hypothalamic–pituitary–gonadal (HPG) axis by impairing the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), mediated through reduced kisspeptin signaling, growth hormone (GH) resistance, and decreased circulating insulin, insulin-like growth factor-1 (IGF-1), and leptin. At the macronutrient level, excess rumen-degradable protein elevates blood urea nitrogen and impairs the uterine environment, while omega-3 polyunsaturated fatty acids inhibit prostaglandin F2α synthesis to support corpus luteum maintenance. At the micronutrient level, selenium, copper, and zinc are essential antioxidant cofactors protecting gametes and embryos from oxidative stress, while vitamins A, D, and E regulate gene expression in reproductive tissues. Furthermore, maternal nutrition during critical gestational windows programs the reproductive capacity of offspring through epigenetic modifications, with profound implications for long-term herd fertility. Understanding these nutritional–reproductive interactions is crucial for developing precision feeding strategies that optimize herd fertility, improve animal welfare, and ensure the economic sustainability of livestock management. A thorough understanding of these nutritional–reproductive interactions is essential for developing precision feeding strategies that optimize fertility in high-producing ruminants. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

Background/Objectives: Sex differences in lung cancer incidence and outcomes are well recognized, yet the relative contributions of sex chromosomes and gonadal sex remain incompletely defined. We aimed to disentangle chromosomal complement and hormonal sex in urethane-induced lung tumorigenesis using the Four Core Genotypes mouse model. Methods: Mice (6–8 weeks old) with independently varied chromosomal complement (XX vs. XY) and gonadal sex received urethane (1 g/kg body weight) weekly for 10 weeks and were evaluated after a 20-week latency period. Tumor multiplicity, tumor area, normalized tumor burden, and Ki-67 proliferation indices were quantified histologically. Hepatic Cyp2e1 expression was measured to assess carcinogen bioactivation. Tumor mutations were analyzed by Sanger sequencing. RAS Q61R immunoreactivity and ERK phosphorylation were evaluated to assess oncogenic signaling. Bronchoalveolar lavage fluid cellularity was analyzed. Survival was monitored. Statistical analyses tested the main effects of chromosomal complement, gonadal sex, and their interaction. Results: Tumor multiplicity (p = 0.0729), tumor area (p = 0.5302), normalized tumor burden (p = 0.5316), and Ki-67 indices (p = 0.6551) did not differ among genotypes. Hepatic Cyp2e1 expression was comparable across groups (genotype p = 0.076; treatment p = 0.445). Sanger sequencing confirmed canonical Kras Q61R mutations. Anti-RAS (Q61R) immunohistochemistry revealed a significant genotype effect on mutant RAS expression (F(3,23) = 3.48, p = 0.032), with the highest H-scores observed in XYF mice compared with male gonadal genotypes; ERK phosphorylation did not differ. Bronchoalveolar lavage fluid analysis revealed increased lymphocytes after urethane exposure without genotype-dependent effects. Survival differed significantly, with XX females demonstrating prolonged survival relative to XY males. Conclusions: Sex influenced survival independently of tumor burden, indicating that sex-associated differences in lung cancer outcomes are likely driven by systemic or microenvironmental factors rather than tumor-intrinsic growth mechanisms. Full article

Several reproductive issues in both men and women are caused by changes in the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). For males to sustain spermatogenesis and Leydig cell function, and for females to ensure orderly folliculogenesis, ovulation, and ovarian steroidogenesis, precise coordination of LH and FSH secretion is necessary. Pituitary responsiveness, the frequency or amplitude of gonadotropin-releasing hormone pulses, or the dysregulation of feedback signals mediated by sex steroids and inhibins all disrupt the balance between LH and FSH secretion. Oligozoospermia, luteal-phase abnormalities, anovulation, or complete spermatogenic failure are possible clinical signs of these alterations. In addition to functional neuroendocrine disturbances, emerging genetic and epigenetic evidence, including pathogenic variants in genes such as gonadotropin-releasing hormone receptor, kisspeptin, kisspeptin receptor, luteinizing hormone beta subunit, follicle-stimulating hormone beta subunit, follicle-stimulating hormone receptor, and luteinizing hormone/choriogonadotropin receptor, has highlighted the role of inherited and acquired molecular defects in disrupting gonadotropin regulation. This narrative review synthesizes contemporary mechanistic, clinical, translational, and genetic evidence elucidating how dysregulated secretion of LH and FSH contributes to reproductive dysfunction. The molecular processes that regulate gonadotropin synthesis and release, as well as neuroendocrine regulation, gene-level determinants of hypothalamic–pituitary–gonadal (HPG) axis dysfunction, and the clinical phenotypes that result from their disruption, are all given special attention. We conclude with a discussion of new treatment strategies that target local intragonadal regulators to enhance gametogenic capacity, modulate gonadotropin signaling, or restore physiological gonadotropin-releasing hormone (GnRH) pulsatility, with consideration of how genetic insights may inform personalized therapeutic approaches. Full article

Gonad loss triggers severe endocrine disorders and altered energy metabolism, yet the precise mechanisms remain poorly understood. In swine production, surgical castration is widely performed to eliminate boar taint and aggressive behavior, but it impairs feed efficiency, increases fat deposition, and raises animal welfare issues. Castration reduces testosterone and estrogen levels, leading to elevated gonadotropin-releasing hormone (GnRH) and its downstream follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Traditionally viewed as a reproductive hormone, FSH has recently emerged as a critical regulator of peripheral metabolism. Based on these findings, we designed and developed a novel FSH vaccine comprising an FSHβ13AA-tandem-ovalbumin conjugate, which has been demonstrated to effectively regulate growth and metabolism in castrated boars. In conclusion, this review underscores the previously underrecognized metabolic functions of follicle-stimulating hormone (FSH) and proposes a novel immunomodulatory strategy targeting FSH for fine-tuning organ function and energy metabolism. This approach shows considerable potential for advancing sustainable, welfare-oriented swine production. Full article

Cyflumetofen (CYF) and its main metabolite, trifluoromethyl benzoic acid (B-1), both of which contain a trifluoromethyl group, are increasingly used in agriculture due to their high stability and efficacy. Structurally, these molecules share several physicochemical features with per- and polyfluoroalkyl substances (PFASs), including endocrine disruption and reproductive toxicity. This study aims to evaluate the reproductive toxicity effects of CYF and its metabolites using adult zebrafish as a model organism. The results indicate that exposure to CYF and B-1 at environmentally relevant concentrations for 21 days causes hormonal disruption and abnormal gonadal development in fish; moreover, as the concentrations increase, CYF and B-1 significantly impair the reproductive capacity of zebrafish and lead to developmental abnormalities in their offspring. Based on the ratio of E2/T and the alteration of key genes in the HPG axis, such as cyp17a2 and cyp11c1, it is hypothesized that CYF and B-1 disrupt hormonal homeostasis via the HPG axis. Notably, male fish were more susceptible when exposed to CYF or B-1, exhibiting sex-specific differences. RNA-seq analysis revealed that CYF/B-1 promotes Ca²⁺ release from the zebrafish brain and induces steroid hormone dysregulation based on the HPG axis via genes such as hsd17a and gnrh. In summary, this study provides key insights into the reproductive toxicity of CYF and its major metabolite, highlighting their risks to the environment and human health. Full article