Search Results (663)

Nile tilapia, as an ideal model for studying sex differentiation, is a popular farmed fish worldwide with a stable XX/XY sex-determination system. In tilapia, ovarian differentiation is triggered by estradiol-17β (E2) production in undifferentiated gonads. In a previous study, we suggested that follicle-stimulating hormone (FSH) signaling might be involved in ovarian differentiation in Nile tilapia. In this study, we further investigated the role of FSH signaling in ovarian differentiation via aromatase expression, which converts testosterone to E2. Masculinization of XX fry by aromatase inhibitor or 17α-methyltestosterone leads to suppression of fshr expression. Feminization of XY fry by E2 treatment increased fshr expression from 15 days after hatching, when E2 treatment was terminated. XX tilapia developed ovaries harboring aromatase expression if fsh and fshr were double knockdowns by morpholino-oligo injections. Finally, the transcriptional activity in the upstream region of the aromatase gene (cyp19a1a) was further increased by FSH stimulation when HEK293T cells were co-transfected with foxl2 and ad4bp/sf1. Collectively, this study suggests that the role of FSH signaling is not critical in tilapia ovarian differentiation; however, FSH signaling may have a compensatory role in ovarian differentiation by increasing cyp19a1a transcription in cooperation with foxl2 and ad4bp/sf1 in Nile tilapia. Full article

The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and the possible mechanisms involving the RAS. Female Wistar rats were divided into the following groups: sham (SHAM), ovariectomized (OVX), OVX and treated with 17β-estradiol (E2) (OE₂), OVX and treated with E2 and drospirenone (OE₂ + DRSP), and OVX and treated with medroxyprogesterone (MPA). Hormonal treatment was delivered via gavage for 28 days. Vascular responses to Ang-(1-7) were assessed in isolated aortic rings, and a Western blot of the thoracic aorta was used to determine the protein levels of angiotensin II (Ang II) type-1 receptor (AT₁R), Ang II type-2 receptor (AT₂R), Ang-(1-7) receptor (Mas), angiotensin-converting enzyme 2 (ACE2), and endothelial nitric oxide synthase (eNOS). The results showed impaired vascular reactivity caused by ovariectomy. Ang-(1-7) induced vasodilation in the OE₂, OE₂ + DRSP, and MPA-treated groups, while the administration of the AT₂R antagonist (PD123319) or the selective Mas antagonist (A779) increased the extent of vasorelaxation induced by Ang-(1-7) in the OVX + MPA group. There were no differences in the aortic levels of AT₁R or ACE2 between the groups, but the MPA group showed significantly increased levels of AT₂R and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters. Full article

This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich (Rex-AG) extracts in ovariectomized rats. Both treatments significantly reduced weight gain and alleviated vaginal dryness, with Rex demonstrating superior thermoregulatory stabilization. Histological and molecular analyses revealed preserved trabecular bone integrity through the downregulation of RANKL and upregulation of TGF-β. Both extracts exhibited potent anti-inflammatory effects in adipose tissue, suppressing IL-6 and TNF-α, while regulating adipogenesis markers (FABP4, KLF, leptin, PPARγ) more effectively than 17β-estradiol. Serum genistein concentrations confirmed its efficient biotransformation and systemic bioavailability. Importantly, the treatments showed favorable safety profiles with no adverse effects on organ weight. These findings establish S. japonicum L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy. Full article

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Estrogen receptor (ER) status is a key determinant in the diagnosis and treatment of BC. Although immunohistochemistry (IHC) is the gold standard for ER assessment, it has limitations. This umbrella review aims to evaluate the role of 16α-18F-fluoro-17β-estradiol ([¹⁸F]FES) PET/CT as a non-invasive imaging tool for assessing ER expression and its implications in BC management. Methods: A comprehensive search was conducted in PubMed/MEDLINE and Cochrane Library for systematic reviews and meta-analyses published in the last decade. Studies eligible for inclusion evaluated the diagnostic accuracy and clinical utility of [¹⁸F]FES PET/CT in BC based on a predefined research question “What is the role of fluoroestradiol ([¹⁸F]FES) PET/CT in breast cancer?”. Data extraction and quality assessment were performed independently by two reviewers using the AMSTAR-2 tool. Results: Eight systematic reviews met the inclusion criteria. [¹⁸F]FES PET/CT demonstrated high sensitivity (81–94%) and specificity (78–95%) in detecting ER-positive lesions. It provided a real-time, whole-body assessment of ER expression, outperforming IHC in detecting functional ER activity. Additionally, [¹⁸F]FES PET/CT showed promise in predicting treatment response and guiding therapy decisions, particularly in metastatic settings. Conclusions: This review highlights the clinical value of [¹⁸F]FES PET/CT in BC management, offering a non-invasive alternative for ER assessment with high diagnostic accuracy. Its integration into clinical practice may enhance personalized treatment strategies for BC patients. Full article

We previously reported that the level of EGFR expression is directly associated with the survival rate of estrogen receptor-positive (ER+) breast cancer patients. Here, we investigated how ER activation by 17β-estradiol (E2), the most potent form of estrogen, affects the expression or activity of EGFR or EGFR-related genes in ER+ breast cancer cells. As expected, E2 enhanced cell proliferation, the induction of S phase, and tumor growth in ER+ breast cancer models. E2 also increased the expression of secretory proteins, including amphiregulin (AREG), angiogenin, artemin, and CXCL16. We focused on AREG, which is a ligand of the epidermal growth factor receptor (EGFR). The levels of AREG expression were positively correlated with ESR1 expression. Our results also showed higher AREG mRNA expression levels in ER+ breast cancer cells than in ER- breast cancer cells. We treated ER+ breast cancer cells with lapatinib to inhibit the AREG/EGFR signaling pathway and then completely inhibited E2-induced cell proliferation and S-phase induction. Similar to the lapatinib treatment, cell proliferation, S-phase induction, cell migration, and tumor growth were suppressed by AREG knockdown. Taken together, we demonstrated that the induction of AREG by E2 contributes to EGFR activation, which then affects cell proliferation and tumor growth. Therefore, we suggest that AREG acts as an intermediary between EGFR and ER and targeting both ERs and EGFRs through combination therapy could prevent tumor progression in EGFR+ ER+ breast cancer patients. Full article

Background: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with a potential risk of developing estrogen-dependent cancers through interactions with estrogen receptor α (ERα). Alternatively, genistein produces estrogenic effects in animals and humans at dietary dosages that act on the nuclear and membrane ERα, estrogen receptor β (ERβ), and the G-protein-coupled estrogen receptor (GPER). These receptors are likely involved in the anxiety symptoms observed in premenstrual disorders. The objective of this study was to evaluate the effects of genistein and 17β-estradiol on anxiety-like behavior and the plasma concentrations of estradiol and progesterone throughout the ovarian cycle of Wistar rats. Methods: The effect of the administration of 0.09 mg/kg of genistein or 17β-estradiol was evaluated using the elevated plus maze (EPM) test, locomotor activity test (LAT), and light/dark box (LDB) test, as well as by assessing the plasma concentrations of estradiol and progesterone, while considering the ovarian cycle phases. Results: Higher levels of anxiety-like behavior were detected in the metestrus–diestrus phase compared to the proestrus–estrus phase, which was associated with low concentrations of estradiol. Genistein, similarly to 17β-estradiol, significantly reduced anxiety-like behaviors in the EPM and LDB; however, 17β-estradiol, but not genistein, significantly increased the plasma estradiol concentration. No significant changes were found in locomotor activity or the plasma progesterone concentrations due to the treatments. Conclusions: These findings suggest that genistein may be useful in the development of alternative therapies to reduce the anxiety associated with low steroid hormone concentrations, which occur in premenstrual syndrome. Genistein could be an alternative to steroidal estrogen therapy to avoid potential side effects due to estradiol or antidepressant treatments, although it still requires medical care. Full article

Background: The oviduct is an organ that participates in multiple critical reproductive processes and provides essential nutritional support while maintaining a specialized microenvironment. It is particularly vulnerable to damage following heat stress-induced hyperthermia. Therefore, mitigating heat-induced damage to oviduct epithelial cells while preserving their physiological integrity under hyperthermia represents a critical therapeutic goal. Objective: This study aims to simulate the cellular damage state in yak oviduct epithelial cells (YOECs) under thermal challenge by increasing the incubation temperature of cultured cells, while observing changes in cellular injury upon supplementation with 17β-estradiol (E₂), in order to explore the underlying cellular regulatory mechanisms involved. Results: After 48 h of exposure to 41 °C, YOECs exhibited elevated HSP70 and HSP90 protein expression levels, reduced OVGP1 protein expression, and increased apoptotic cells. Compared to the 41 °C group, the E₂ + 41 °C group displayed decreased HSP70 protein levels, increased OVGP1 protein expression, and reduced apoptotic cell numbers. Additionally, changes in endoplasmic reticulum calcium ion (ER-Ca²⁺) distribution and fluorescence intensity variations in ER-Ca²⁺ regulatory proteins SERCA and IP3R3 were analyzed in the 37 °C, 41 °C, and E₂ + 41 °C groups. The ER-Ca²⁺ distribution pattern in the E₂ + 41 °C group remained similar to that of the 37 °C group. However, the fluorescence intensity levels of SERCA and IP3R3 proteins in the E₂ + 41 °C group did not recover to levels comparable to the 37 °C group. Conclusion: These findings suggest that E₂ may mitigate thermal challenge-induced cellular damage in YOECs by maintaining ER-Ca²⁺ homeostasis, thereby preserving cellular functionality under elevated temperatures. Full article

Malaria, the deadliest parasitic disease in the world, is sexually dimorphic, inflammatory, and oxidative. Males experience more severe symptoms and mortality than females do; therefore, the roles of 17β-estradiol and testosterone in this phenomenon have been studied. Both hormones affect oxidative stress, the primary mechanism of Plasmodium elimination. Estradiol has antioxidant activity, but the role of testosterone is controversial. Testosterone increases oxidative stress by reducing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, which increase lipoperoxidation in the testis. However, the antioxidant properties of testosterone in prostate and nervous tissue have also been reported. The discrepancies are probably because when testosterone levels increase, the aromatase enzyme transforms testosterone into estrogens that possess antioxidant activity, which masks the results. Therefore, it is unknown whether testosterone is involved in the sexual dimorphism that occurs in oxidative stress in malaria. In this work, we administered testosterone and simultaneously inhibited aromatase with letrozole to evaluate the role of testosterone in the sexually dimorphic pattern of oxidative stress that occurs in the blood, spleen, and brain of male and female CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). Testosterone triggers parasitemia in males, who also display more oxidative stress than females in the absence of infection, leading to sexually dimorphic patterns. Interestingly, increasing testosterone levels in infected mice reduced oxidative stress in males and increased oxidative stress in females, reversing or eliminating the dimorphic patterns observed. Oxidative stress varies in each tissue; the brain was the most protected, while the blood was the greatest damaged. Our findings highlight the role of testosterone as a regulator of oxidative stress in a tissue and sex-specific manner; therefore, understanding the role of testosterone in malaria may contribute to the development of sex-specific personalized antimalarial therapies. Full article

Several plant-associated microbes have the capability of ameliorating the adverse effects of salinity stress in plants. Such microbes produce metabolites, including proline, glycine betaine, and secondary compounds, like melatonin, traumatic acid, and β-estradiol, which have been found to have a role in reducing salinity-induced damage in plant cells. While the effects of these metabolites have been studied, their application-related aspects remain underexplored. In this study, we investigated the salinity-stress-alleviating potential of metabolites derived from the endophytic bacterium Bacillus safensis BTL5. The microbial metabolites were extracted using the hexane–chloroform fraction method and identified through LC-HRMS analysis. Four metabolites (traumatic acid, β-estradiol, arbutin, and α-mangostin), along with a fifth compound, melatonin, were initially screened for their salinity alleviation potential. Subsequently, two metabolites, i.e., arbutin and β-estradiol, were evaluated for their impact on growth parameters and enzymatic antioxidant activities under 200 mM salt stress. The results revealed that arbutin and β-estradiol significantly improved plant growth, chlorophyll content, and enzymatic activities while reducing oxidative damage. The dose-dependent effects highlighted optimal concentrations for maximum efficacy from these compounds under elevated salinity. This study signifies the potential of microbial metabolites in enhancing crop resilience to salinity, highlighting their role in sustainable agriculture. The outcomes of this study provide a baseline for the applied use of such microbial metabolites under field conditions. Full article

17β-estradiol (E2) contamination resulting from the widespread use of animal manure poses a new threat to the agricultural environment. Since anaerobic environments have been reported to significantly extend the persistence of E2, estrogen pollution of anaerobic farmland soils (e.g., paddy soils) is of particular concern, necessitating the development of in situ high-efficiency E2 bioremediation microorganisms. In this work, six E2-degrading strains were isolated from paddy soils, including strains from Elizabethkingia, Stenotrophomonas, Microbacterium, Ochrobactrum, Gordonia, and Acinetobacter. Among these strains, Ochrobactrum sp. AEPI-SP11 and Acinetobacter sp. AEPI-SP17 were able to degrade over 90% of 20 mg/L E2 within 5 days. Although both AEPI-SP11 and AEPI-SP17 exhibited strong tolerance to pH, temperature, and initial E2 concentrations (2, 5, 20, and 50 mg/L), only AEPI-SP17 was capable of biodegrading E2 under anaerobic conditions. Based on genomic analysis, we further obtained the whole genome sequences of AEPI-SP11 and AEPI-SP17 and identified and compared potential genes responsible for estrogen degradation in the two strains. Overall, this work significantly enhances our understanding of E2-degrading strains in paddy soils, offers valuable insights into the degradation mechanisms under varying conditions, and provides potential microbial resources for the effective control of E2 pollution in farmlands. Full article

Background: Diabetes mellitus induces profound metabolic and endocrine alterations, impacting reproductive function through oxidative stress and hormonal imbalances. This study investigated the effects of alloxan-induced diabetes on hormonal status and oxidative stress in female Wistar rats. Methods: A synthetic sulfonamide derivative (compound S) was obtained via chemical synthesis and characterized by elemental and spectral analysis. Salvia officinalis extract was phytochemically profiled using UHPLC-HRMS and assessed for antioxidant potential using DPPH, ABTS, and FRAP assays. The synthetic compound and the plant extract, along with metformin were evaluated in vivo for their potential antihyperglycemic, hormone-regulating, and antioxidant properties., Serum levels of progesterone, estradiol, and follicle-stimulating hormone (FSH) were evaluated alongside oxidative stress biomarkers transforming growth factor-beta 1 (TGF-β1) and glutathione peroxidase 3 (GPX3). Results: Diabetic rats (untreated) exhibited a significant decrease in estradiol (22.00 ± 4.1 pg/mL vs. 54.74 ± 17.5 pg/mL in controls, p < 0.001) and an increase in progesterone levels (17.38 ± 9.6 ng/mL vs. 3.59 ± 0.90 ng/mL in controls, p < 0.05), suggestive for ovarian dysfunction. TGF-β1 levels were elevated in diabetic rats (27.73 ± 19.4 ng/mL vs. 21.55 ± 13.15 ng/mL in controls, p < 0.05), while increased serum GPX3 (61.50 ± 11.3 ng/mL vs. 38.20 ± 12.84 ng/mL in controls, p < 0.05) indicates enhanced oxidative stress. Statistical analysis revealed a correlation between serum GPX3 levels, FSH (p = −0.039), and estradiol (p = −0.025) in the diabetic group (L2). Conclusions: These findings contribute new evidence regarding the effects of diabetes on reproductive hormones and oxidative stress in female models. Full article

17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca²⁺]_i transients were measured in mechanically non-loaded CM, and the tension–length relationship was studied in CM mechanically loaded by carbon fibers. The actin–myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca²⁺]_i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension–length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT. Full article

Background: This paper briefly reviews the most important endocrine features of primary ovarian insufficiency (POI) and shows their relevance for the diagnosis and treatment of this condition. Introduction: Endocrine disturbances in POI cause problems for both the fertility and general health status of the affected women. Both subfertility and infertility result from the depletion of growing ovarian follicles which, in its turn, is the causative factor of hypoestrogenism; this is responsible for most of the general health problems affecting women. Method: Search of literature. Results and conclusion: A combination of high-serum follicle-stimulating hormone (FSH) and low 17β-estradiol (E2) concentrations is a key feature characterizing POI and is the decisive element for POI diagnosis. However, an in-depth search for possible genetic and non-genetic causes is important for adequate counseling regarding prevention and early intervention. The treatment of general health problems, based on correcting hypoestrogenism through hormone replacement therapy (HRT), is relatively easy. On the other hand, resolving infertility is a much more difficult task, and oocyte donation is the only really efficient instrument. Fertility preservation is a suitable alternative in patients with early POI diagnosis, in whom some viable follicles are still present in the ovaries. In patients who refuse oocyte donation, intraovarian injection of autologous platelet-rich plasma and in vitro activation of dormant follicles may be considered. Other innovative treatments, such as stem cell therapies or nuclear transfer, are currently under investigation. Full article

During the current outbreak of Marburg virus disease (MVD) in Rwanda, we synthesized evidence from the literature to improve case management. Accordingly, experimental treatment was offered to patients under close follow-up. Remdesivir alone or in combination with monoclonal antibody treatment (MBP091) complemented with supportive care has improved the clinical outcomes of patients. Additionally, we have identified several experimental therapies currently under investigation, including antiviral drugs such as favipiravir, galidesivir, obeldesivir, and remdesivir, along with monoclonal and polyclonal antibodies (e.g., polyclonal IgG, monoclonal antibody MR-78-N; MR82-N; MR191-N; monoclonal antibodies MR186-YTE and MBP091). Furthermore, substantial progress is being made in vaccine development, with promising candidates including adenovirus-vectored vaccines, DNA vaccines, and the recombinant vesicular stomatitis virus (rVSV) vaccine. Moreover, innovative preventive and treatment strategies—such as synthetic hormones like estradiol benzoate, small interfering RNA (siRNA), interferon-β therapy, and phosphorodiamidate morpholino oligomers—are emerging as potential options for MVD management. Further investment is needed to accelerate research and optimize these therapeutics and preventive modalities. Additional epidemiological, preclinical, and clinical studies are warranted to generate the evidence required to inform policymaking, resource mobilization, and the implementation of cost-effective interventions for the prevention, control, and treatment of MVD. Full article

For many years, there has been increasing concern about the effects of the presence of hazardous substances in the environment. The chemical and biological effect (BE) monitoring of these pollutants has proven difficult due to low environmental concentrations, variable bioavailability, and the generalised nature of ecological responses to these substances. The over- or under-expression of key genes has proven to be useful in understanding the molecular mechanisms of the toxicity of contaminants. This study uses a quantitative PCR array to detect the changes in gene expression in flounder livers after exposure to both laboratory- and field-based contaminants. The model contaminants included 17β-estradiol (E2), 3-methylcholanthrene (3-MC), a commercial mixture of polychlorinated biphenyls (PCB, Arochlor), perfluoroctanoic acid (PFOA), and lindane. Multivariate analysis was used to investigate relationships between higher-organisational-level biomarkers, supporting parameters, and genes. A scoring system enabled the visualisation of biological effect responses and contaminants in field samples. Although gene expression was useful for inferring the pathways of toxicity in this organism, we recommend that this array be used in combination with existing and recommended higher-level biomarkers and should not be used as a replacement for traditional biomarkers currently used in monitoring. Full article