Semi-extensive goat production in Mediterranean environments is increasingly exposed to strong seasonal thermal fluctuations that may affect animal health and reproductive performance. This study aimed to assess the effects of summer heat and winter cold on local buck goats through a structured survey of goat farmers combined with seasonal blood biochemical and immunological profiling, reproductive and stress hormone assays, semen quality evaluation, and seminal plasma analysis. Farmers widely identified summer as the most challenging season, mainly due to forage scarcity and reduced animal appetite. Biochemically, most parameters remained stable across seasons; however, calcium, total protein, lactate dehydrogenase, cholesterol, and glucose showed significant seasonal variation, with higher Ca, total protein, and LDH in winter and elevated cholesterol and glucose in summer. Reproductively, luteinizing hormone and follicle-stimulating hormone were significantly higher in summer, while testosterone and cortisol were unaffected. Semen quality was largely resilient to seasonality, except for a higher ejaculate volume in summer. In contrast, seminal plasma composition was superior in winter, with significantly higher total protein, cholesterol, lipids, fructose, and citric acid. In conclusion, seasonal climatic stress distinctly modulates metabolic and reproductive physiology in buck goats, highlighting the importance of adaptive management strategies in Mediterranean semi-extensive systems.

The optimal approach to hormonal treatment aimed at increasing penis size has been established for infant males with micropenis; however, data are limited in partial androgen insensitivity syndrome (PAIS). We report a 6-month-old male patient treated with intramuscular testosterone for micropenis. At birth, he presented with atypical genitalia, including a microphallus, hypospadias, and a bifid scrotum. His karyotype was 46,XY, and endocrine evaluation revealed normal testicular function. A novel missense variant of the AR gene (p.G578E) was identified. Intramuscular testosterone enanthate 62.5 mg/dose was administered every 4 weeks for 3 doses (6-8 months). Stretched penile length increased from 18 to 30 mm (+67%) without adverse events. During treatment, luteinizing hormone secretion was suppressed, with trough levels falling below the limit of detection, consistent with androgen-mediated negative feedback. Luteinizing hormone levels during mini-puberty in response to testosterone treatment, supporting testosterone therapy in patients with PAIS.

The present study evaluated the combined germ cell effects of monosodium glutamate (MSG) and bisphenol A (BPA) on juvenile Sprague Dawley rats. Animals were orally exposed to low and high doses of MSG and BPA, individually and in combination, for a consecutive duration of eight weeks. Combined exposure significantly reduced body weight and increased micronucleus formation, indicating systemic genotoxicity. Oxidative stress was demonstrated by elevated MDA, reduced GSH and catalase activity, and increased 8-OHdG expression. Sperm count, motility, chromatin integrity, and ultrastructure were significantly impaired. Histological and protein analyses confirmed testicular degeneration and molecular alterations. Hormonal imbalance was observed by decreased serum testosterone, LH, FSH, and reduced 17β-HSD expression, which suggested not only testicular dysfunction but also the involvement of the central hypothalamic-pituitary axis. Inflammation was evident with elevated TNF-α and testicular MPO activity, accompanied by activation of p-NF-κB p65/NLRP3/caspase-1/IL-18 axis. Bax-mediated apoptosis was elevated, while p-AMPK/AMPK downregulation suggested impaired energy metabolism. These findings demonstrated that combined MSG and BPA exposure induced oxidative stress, inflammation, apoptosis, and hormonal imbalance, leading to germ cell toxicity.

Polycystic ovary syndrome (PCOS) is driven by multiple factors, but detailed mechanisms in the setting of PCOS remains unclear. Our study is to comprehensively clarify the potentially molecular mechanisms of effect Formulae Q (Traditional Chinese Medicine) on PCOS. A model of PCOS-liked rats induced by letrozole (1 mg/kg/d) for 21days was performed. Formulae Q (20 g/kg/d) was orally gavaged twice daily to rats as a pretreatment, and metformin (100 mg/kg/d) was orally gavaged daily as a positive control. HE stains were performed to assess pathological changes of the ovaries, and the number of corpuses luteum and cysts were assessed. Biochemistry test was used to measure testosterone, E2, FSH, LH, AMH and LH/FSH in serum. All the target proteins were identified by proteomics and bioinformatics analyses, and then verified by qPCR. The core components of Formulae Q identified by UPLC-MS/MS were subjected to molecular docking with target proteins.As a result, Formulae Q had a obviously protective-effect against PCOS by reversing alters of hormone levels in serum and pathology in ovary tissues. Proteomics data are available via ProteomeXchange with identifier PXD057910. Formula Q significantly inhibited Zp family related indexes (Zp2, Zp3 and Zp4). Furthermore, pharmachologic effectts of Formula Q were closely related to steroidogenesis metabolism (Cyp17a1, Ass1 and Apoc1), synthesis and metabolism processes (Cbr1l1, Fdx1 and Dpep1), signaling and cellular processes (Calb2, Dcn and Reep6), and the other biological processes (Fdx1, Hdgfl3, Lgals1 and Tagin). The Cbr1l1 protein showed strong binding affinity with the four core components of Formulae Q.These findings suggest that Formulae Q may hold promise as a potential candidate for PCOS management.

Testosterone is an essential androgenic steroid traditionally produced from 4-androstenedione through multistep chemical or biocatalytic processes. Here, we report a streamlined and sustainable "two-stage" bioconversion strategy for direct testosterone production from phytosterols. In the first stage, Mycobacterium neoaurum NRRL B-3805 was metabolically reprogrammed to maximize 4-androstenedione accumulation by deleting kstd1 and kshB1 and overexpressing hsd4A, generating strain MnBΔkstd1/ΔkshB1/p261-hsd4A. This engineered strain produced 12.3 g L- 1 of 4-androstenedione within 6 days, corresponding to a molar yield exceeding 88%. In the second stage, structure-guided redesign of ketoreductase markedly enhanced its catalytic efficiency toward 4-androstenedione. Molecular docking and dynamics analyses identified residues G141 and M215 as critical contributors to substrate recognition. The G141A substitution optimized the local binding environment by modulating hydrophobic and polar interactions, leading to a 5.1-fold increase in catalytic efficiency. Under optimized reaction conditions, the engineered enzyme achieved complete conversion of in situ-generated 4-androstenedione to testosterone in a single bioreactor, yielding 12.05 g/L of testosterone with an overall molar yield of 86% from phytosterol and delivering a record spatiotemporal productivity of 0.6 g L- 1 h- 1. By eliminating intermediate 4-androstenedione extraction and purification, this integrated strategy establishes a cost-effective and environmentally sustainable route for industrial testosterone manufacture. More broadly, our work illustrates how synergistic metabolic engineering and structure-guided enzyme design can be combined to accelerate steroid biomanufacturing.

Testosterone deficiency (TD) is a prevalent and underdiagnosed condition associated with adverse metabolic and cardiovascular outcomes. The remnant cholesterol to high-density lipoprotein cholesterol ratio (RC/HDL-C) has emerged as a novel lipid marker reflecting both atherogenic burden and metabolic dysfunction. However, its relationship with testosterone levels remains unclear. We analyzed data from 2782 adult men aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. TD was defined as total testosterone (TT) < 300 ng/dL. RC/HDL-C was calculated as (total cholesterol - LDL-C - HDL-C)/HDL-C. Multivariable survey-weighted linear and logistic regression models were used to evaluate the association between RC/HDL-C and TT levels and TD risk. Generalized additive models were applied to assess nonlinear relationships, and receiver operating characteristic (ROC) curve analysis was performed to evaluate discriminative performance. Higher RC/HDL-C was significantly associated with lower TT and increased odds of TD. In the fully adjusted model, each unit increase in RC/HDL-C was associated with a 52.25 ng/dL decrease in TT (β = -52.25, 95% CI:-74.64 to-29.85, P < .0001), and 81% higher odds of TD (OR = 1.81, 95% CI: 1.36 to 2.41, P < .001). Compared to the lowest RC/HDL-C quartile, individuals in the highest quartile had significantly lower TT levels (β = -74.47, 95% CI:-107.81 to-41.13) and higher TD risk (OR = 2.25, 95% CI: 1.24 to 4.07). Subgroup analyses confirmed consistent associations across age, BMI, metabolic status, and lifestyle factors. Smooth curve fitting revealed monotonic relationships. The RC/HDL-C ratio demonstrated superior discriminatory ability for TD (AUC = 0.647) compared to RC (AUC = 0.633) and HDL-C (AUC = 0.619). High RC/HDL-C ratio is associated with a higher likelihood of TD, though the cross-sectional nature of this study limits the ability to establish causality.