Environmental pollutants adversely affect both adult organisms and their offspring. Prednisone, a synthetic glucocorticoid frequently detected in surface water, harms aquatic organisms like sheepshead minnows, tadpoles, and zebrafish (Danio rerio). However, data on its effects on the thyroid endocrine system of zebrafish and its intergenerational toxicity are currently lacking. This study exposed adult male zebrafish to environmentally relevant prednisone concentrations (0-500 ng/L) for 60 days to explore potential thyroid endocrine disruption in both parents and offspring. Research findings show that compared with the control group, zebrafish in the high-dose (H) group had significantly reduced body length and weight. Their swimming speed decreased by 20.9-32.7%, the time spent stationary at the bottom of the tank decreased by 139.1-152.1%, and the frequency of this behavior dropped by 84.6-94.2%. As prednisone concentrations increased, the plasma levels of T4 in parental zebrafish decreased significantly, while the levels of T3 and TSH increased significantly. Thyroid follicular epithelial cells exhibited hyperplasia and hypertrophy along with a depletion of colloid cells. These effects were associated with abnormal transcriptional levels of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis (i.e., crh, pax8, tpo, tg, ttr and dio1 and dio2). Additionally, parental exposure to prednisone impaired F1 larvae: 82.3% increased mortality, 14.3-32.2% reduced hatching rates, abnormal heart rates, 29.16-38.76% reduced swimming activity, decreased thyroid hormones, and dysregulated transcription of HPT axis-related genes. The study confirms that prednisone induces intergenerational toxicity in parents and offspring by disrupting thyroid endocrine function, enhancing understanding of the risks posed by prednisone to fish.

Intestinal remodeling during amphibian metamorphosis is essential for adaptation to terrestrial environments. In this study, Pelophylax nigromaculatus tadpoles at developmental stage G26 were exposed to near-environmental concentrations of MC-LR until the end of metamorphosis to investigate whether and how MC-LR affects intestinal remodeling during metamorphosis in tadpoles. Furthermore, parents exposed to MC-LR and those unexposed were cross-matched to determine if tadpoles from the first filial generation (F1) affected intestinal remodeling. MC-LR exposure hindered the proliferation of adult intestinal stem cells and impaired their differentiation into adult epithelial cells during metamorphosis. MC-LR exposure caused pathological damage to thyroid tissue, downregulated thyroid hormone synthesis genes, and reduced blood concentrations of hypothalamic-pituitary-thyroid axis hormones (CRH, TSH, and T3) and transthyretin. Molecular docking analysis suggests that MC-LR may compete with T3 for TTR binding. T3-regulated Notch and Wnt signaling pathways, along with key intestinal remodeling genes (msi, pcna, and lgr5) controlled by these pathways, were downregulated. Thus, MC-LR inhibits Notch and Wnt signaling pathways' responses by interfering with thyroid hormone synthesis and transport, ultimately impairing tadpoles' intestinal remodeling to some extent. Moreover, transgenerational analysis revealed that the disruption of intestinal remodeling also occurred in F1 tadpoles. MC-LR exposure increased DNA methylation levels in parental gonads, as well as in the brains and thyroids of F1 tadpoles. DNA methylation levels negative correlation with the blood T3 concentration and the severity of intestinal remodeling disruption. This research pioneers the investigation of how environmentally relevant concentrations of Microcystin-LR affect intestinal remodeling during amphibian metamorphosis, creating a basis for future assessments of Microcystin-LR exposure risks to amphibian populations.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated not only with tumor progression but also with profound metabolic and nutritional disturbances. Thyroid hormone homeostasis may reflect this systemic response; however, perioperative data in PDAC remain limited. We aimed to assess perioperative changes in thyroid-related parameters in patients with PDAC undergoing different types of surgical management and to explore their associations with nutritional, metabolic, and tumor-burden variables. Methods: We performed a retrospective single-center study including 101 patients with PDAC. Thyroid-related and metabolic laboratory parameters were assessed before surgery and again 4-6 weeks later. The analyzed variables included thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), the FT3/FT4 ratio, albumin, total protein, glucose, insulin, HbA1c, lipid parameters, and CA 19-9. Patients were analyzed according to resectional versus non-resectional treatment and according to four procedure types. The primary endpoint was perioperative change in the FT3/FT4 ratio. Results: At baseline, resectional patients had significantly higher FT3 and FT3/FT4 ratio values and lower FT4 and CA 19-9 levels than non-resectional patients. In the whole cohort, FT3 and the FT3/FT4 ratio decreased significantly after treatment, whereas TSH increased, and FT4 remained unchanged. These endocrine changes occurred in parallel with significant declines in albumin, total protein, glucose, insulin, HbA1c, and HDL cholesterol, together with an increase in triglyceride levels. Baseline FT3 and FT3/FT4 ratios correlated positively with albumin and total protein and negatively with CA 19-9. Although perioperative changes did not differ significantly between resectional and non-resectional groups except for triglycerides, significant procedure-dependent differences were observed across the four surgical categories for FT3, FT4, TSH, and the FT3/FT4 ratio; glucose; insulin; and triglycerides. The prevalence of low-T3 syndrome increased from 11.1% preoperatively to 38.7% postoperatively. Conclusions: In PDAC, perioperative changes in thyroid hormone indices are pronounced and strongly depend on the type of surgical management. FT3 and the FT3/FT4 ratio appear to reflect systemic metabolic and nutritional adaptation as well as disease burden rather than acting as tumor-specific markers.

Primary mitochondrial diseases (PMD) are rare disorders with limited therapeutic options. Coenzyme Q10 (CoQ10) supplementation is widely used, although formulation differences can affect absorption and efficacy. This open-label pilot feasibility trial evaluated a food for special medical purposes (FSMP) containing high-dose CoQ10 (250 mg per capsule) in patients with PMD. Ten patients (mean age: 55.5 ± 8.6 years) were enrolled. Serum/plasma biomarkers, including CoQ10, fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), ferric-reducing antioxidant power (FRAP), total sulfhydryl groups (t-SH), and advanced oxidation protein products (AOPP), were assessed at baseline (T0, after ≥30 days of conventional ubidecarenone) and after 30 days of FSMP administration (T1). Fatigue severity scale (FSS) and 5-times sit-to-stand test (5xSST) were evaluated at both timepoints. FSMP was administered at 250 or 500 mg/day. Twenty sex- and age-matched healthy controls were included for CoQ10 comparison. Absolute CoQ10 concentrations remained stable overall at T1, with all patients maintaining levels above 390 ng/mL (100% vs. 60% at T0), although concentrations remained lower than in healthy controls (p < 0.01). Dose-normalized CoQ10 exposure was significantly higher with FSMP versus conventional ubidecarenone (p < 0.001, Cohen's d = 7.31). FGF21, GDF15, AOPP, and t-SH remained unchanged, whereas FRAP increased at T1 (p < 0.01). No significant changes were observed in 5xSST and FSS. Exploratory analyses indicated inter-individual variability in functional responses. FSMP was associated with higher dose-normalized systemic CoQ10 exposure, more consistent circulating CoQ10, and increased FRAP levels. Its simplified dosing regimen may support long-term adherence. Larger studies are warranted to validate these preliminary findings.

Infertility is an increasing concern for many women and can affect both physical and emotional well-being. The central nervous system (CNS) -particularly the hypothalamus, pituitary gland, and pineal gland - plays a crucial role in female reproductive health. We conducted a narrative review of relevant studies published between 2015 and 2025, sourcing data from PubMed and Scopus. Our goal was to investigate how dysregulation of hormones from the hypothalamus, pituitary gland, and pineal gland contributes to fertility-related disorders, such as impairments in ovulation, oocyte quality, and embryo development. Both human and significant animal studies were considered to better understand how CNS hormones affect fertility. The findings emphasize the roles of key hormones, including gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), melatonin, Adrenocorticotropic Hormone (ACTH), Thyroid-Stimulating Hormone (TSH), and vasopressin (ADH). The proper timing and balance of these hormones are vital. For instance, GnRH pulses regulate the release of LH and FSH, which are essential for ovulation and follicle development. Melatonin supports oocyte health and helps maintain the menstrual cycle, while ACTH and TSH are also involved in reproductive function. Vasopressin contributes by affecting uterine activity and hormone production. Understanding these hormonal interactions may lead to better diagnostic tools and more effective treatment strategies for conditions such as polycystic ovary syndrome (PCOS) and other fertility-related disorders. Unlike previous studies, this research provides a comprehensive investigation of how CNS-mediated hormonal regulation influences female reproductive outcomes, examining the roles of all involved hormones.

The U.S. Army Ranger Training Course (RTC) is a multi-stressor environment including cognitive and physical stress coupled with repeated sleep and energy deficits over 61+ days. Previous investigations of physiological responses to RTC operational stressors were conducted exclusively in males, leaving female responses uncharacterized. Therefore, this study aimed to identify changes in metabolic, growth, and sex hormones, inflammatory and iron markers in males and females undergoing RTC. Blood samples and body composition assessments (DXA) were collected at the start of RTC (Baseline (BL)) and at the end of each phase (Phase (P)1 - general field, P2 - mountains, P3 - swamp). During each phase, daily urine sampling and measures of energy balance (doubly labeled water method) occurred. Females experienced physiological changes primarily in P2, with reductions in estradiol (mean difference [95% Confidence Interval]: -79.29 [-115.32, -43.26]), progesterone (-1.48 [-2.70, -0.26]), testosterone (-0.74 [-1.43, -0.04]), free testosterone: -12.70 [-23.23, -2.17]), thyroid stimulating hormone (TSH; -0.54 [-1.03, -0.05]), and insulin-like growth factor 1 (IGF-1; -92.58 [-121.28, -63.88]) compared to BL. Males demonstrated significant decreases in free testosterone, TSH, triiodothyronine (T3), IGF-1, hemoglobin, and hematocrit across all three phases compared to BL (all, p < 0.05), with the largest changes in P3 for TSH (-0.66, [-1.21, -0.11]), T3 (-0.30 [-0.41, -0.20]), IGF-1 (-104.70 [-116.52, -92.88]), hemoglobin (-1.32 [-1.71, -0.94]), and hematocrit (-3.89 [-5.02, -2.75]). Ferritin increased across all phases compared to BL regardless of sex (p < 0.05). These findings indicate that multi-stressor environments may disproportionately affect male physiological markers, whereas females exhibited fewer, phase-specific changes.