Search Results (25)

Estrogenic chemicals are widely distributed and structurally diverse. They primarily disrupt estrogen-related metabolism in animals or humans by mimicking the agonistic receptor effects of natural estrogens, thereby influencing the transcription of estrogen receptors to regulate their quantity and sensitivity. This disruption of estrogen-related metabolism can lead to estrogen-related effects, posing risks to biological health, emphasizing the urgent need for simple and effective methods to screen compounds with estrogenic effects. Herein, a new electrochemical biological effect biosensor based on human estrogen receptor α (hERα) is developed, which uses hERα as the biorecognition element and employs the electroactive horseradish peroxidase (HRP) labeled 17β-estradiol (E2) multifunctional conjugate HRP-E2 as the signal-boosting element and ligand competition agent. Based on the specific ligand–receptor interaction principle between the target and nuclear receptor, by allowing the test compound to compete with HRP-E2 conjugate for binding to hERα and testing the electrocatalytic signal of the conjugate that fails to bind to the hERα estrogen receptor, rapid screening and quantitative detection of chemical substances with estrogenic effect have been achieved. The biosensor shows a wide linear range of 40 pM to 40 nM with a detection limit of 17 pM (S/N = 3) for E2, and the detection limit is 2 orders of magnitude better than that of the previously reported sensors. The biosensor based on ligand–receptor binding can not only quantitatively analyze the typical estrogen E2, but also evaluate the relative estrogen effect strength of other estrogen compounds, which has good stability and selectivity. This electrochemical sensing platform displays its promising potential for rapid screening and quantitative detection of chemicals with estrogenic effects. Full article

In this study, we created a 3D Artificial Skin Platform that can be used for the treatment of pigmentation by artificially realizing the skin of pregnant women. For the stable realization of 3D artificial skin, a bilayer hydrogel composed of collagen type I and fibrin was designed and applied to the study to reduce the tension-induced contraction of collagen type I, the extracellular matrix (ECM) of artificial skin, by dynamic culture. Oxygen concentration and 17β-Estradiol (E2) concentration, which are highly related to melanin production, were selected as parameters of the pregnancy environment and applied to cell culture. Oxygen concentration, which is locally reduced in the first trimester (2.5–3%), and E2, which is upregulated in the third trimester, were applied to the cell culture process. We analyzed whether the 3D artificial skin implemented in the 3D Artificial Skin Platform could better represent the tendency of melanin expression in pregnant women than cells cultured under the same conditions in 2D. The expression levels of melanin and melanin-related genes in the 2D cell culture did not show a significant trend that was similar to the melanin expression trend in pregnant women. However, the 3D artificial skin platform showed a significant trend towards a 2-6-fold increase in melanin expression in response to low oxygen concentrations (2.5%) and E2 concentrations (17 ng/mL), which was similar to the trend in pregnant women in vivo. These results suggest that 3D artificial skin cultured on the Artificial Skin Platform has the potential to be used as a substitute for human pregnant skin in various research fields related to the treatment of pigmentation. Full article

Background: Sex difference in the immune response may influence patients’ response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Method: Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Result: Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7–43); p < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89–23.35); p < 0.0001]. Conclusions: High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs. Full article

Marfan syndrome causes a hereditary form of thoracic aortic aneurysms with worse outcomes in male compared to female patients. In this study, we examine the effects of 17 β-estradiol on aortic dilation and rupture in a Marfan mouse model. Marfan male mice were administered 17 β-estradiol, and the growth in the aortic root, along with the risk of aortic rupture, was measured. Transcriptomic profiling was used to identify enriched pathways from 17 β-estradiol treatments. Aortic smooth muscle cells were then treated with cytokines to validate functional mechanisms. We show that 17 β-estradiol decreased the size and rate of aortic root dilation and improved survival from rupture. The Marfan transcriptome was enriched in inflammatory genes, and the addition of 17 β-estradiol modulated a set of genes that function through TNFα mediated NF-κB signaling. In addition, 17 β-estradiol suppressed the induction of these TNFα induced genes in aortic smooth muscle cells in vitro in an NF-κB dependent manner, and 17 β-estradiol decreased the formation of adventitial inflammatory foci in aortic roots in vivo. In conclusion, 17 β-estradiol protects against the dilation and rupture of aortic roots in Marfan male mice through the inhibition of TNFα-NF-κB signaling. Full article

The common snook (Centropomus undecimalis) is a protandric hermaphrodite fish that undergoes a sex change during its life cycle. In nature, common snook females develop directly from males shortly after spawning. However, the factors triggering this process remain unknown. This knowledge gap poses challenges for managing the species in captivity. To address this, we conducted a study on sex change induction in three-year-old males using estradiol and evaluated the potential effects of photoperiod manipulation on early maturation. Four treatment groups were employed: (1) fish with estradiol + natural photoperiod; (2) fish without estradiol + natural photoperiod; (3) fish without estradiol + controlled photoperiod; and (4) fish with estradiol + controlled photoperiod. The effectiveness of these treatments was assessed through histological procedures, which allowed for the examination of the fishes’ gonads. Furthermore, the concentration of alkali labile phosphorus in fish plasma was measured and correlated with the histological results. Our findings revealed that administering 2 mg/kg estradiol implants resulted in a remarkable 100% female population within the estradiol-treated groups. No significant effect on fish maturation was observed due to the manipulated photoperiod conditions. This protocol offers improved management strategies for captive broodstock. Firstly, the concentration of estradiol used in this study proved sufficient to induce sex change in this hermaphroditic species, enabling the production of viable females at an early age and smaller size and facilitating easier broodstock manipulation. Secondly, the implementation of the alkali labile phosphorus technique allows for sex identification without the need to sacrifice the fish. In conclusion, our study provides valuable insights into sex change induction and photoperiod manipulation in common snook. The findings contribute to enhanced management practices for captive broodstock. However, further research is needed to explore the underlying mechanisms triggering sex change and to optimize protocols for long-term maintenance and successful reproduction in captivity. Full article

Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell–cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells. Full article

Among Chinese soft-shelled turtles, Pelodiscus sinensis, males have a richer nutritional value and higher market price than females. All-male offspring were obtained by 17β-estradiol (E2). However, the molecular mechanisms of E2 inducing sexual reversal remain unclear. In this study, we cloned estrogen nuclear receptors (ERs) from P. sinensis and investigated their expression profiles. We examined the responses of ERα and ERβ after treatment with different concentrations of 1.0, 5.0, and 10 mg/mL E2. ERs showed abundant expressions in the adult gonad, ERα for ovary, and ERβ for testis. E2 can up-regulate the expression of ERα, which showed a remarkable increase while the promotion of ERβ was unobvious. They reached a high level at stage 17 after the treatment of E2, genes of the female-related genes Rspo1, Wnt4, β-catenin, Foxl2, Cyp19a1, and Sox3 exhibited a significant raise at stage 17 with the increase in the concentration of E2 while the male-related genes Sox9, Dmrt1, and Amh were significantly inhibited. Our study cloned the full length of ERs and analyzed their structures and expressions, laying a foundation for the further study of the effect of estrogen on sex determination. Full article

The purpose of this study was to investigate the effects of BMP6 on the function of goat ovarian granulosa cells (GCs). The results showed that the exogenous addition of BMP6 did not affect the EdU-positive ratio of ovarian GCs and had no significant effect on the mRNA and protein expression levels of the proliferation-related gene PCNA (p > 0.05). Meanwhile, BMP6 had no significant effect on the cycle phase distribution of GCs but increased the mRNA expression of CDK4 (p < 0.05) and CCND1 (p < 0.01) and decreased the mRNA expression of CCNE1 (p < 0.01). Moreover, BMP6 had no significant effect on the apoptosis rate of GCs and did not affect the mRNA expression levels of apoptosis-related genes BAX, BCL2, and Caspase3 (p > 0.05). Importantly, BMP6 upregulated the secretion of 17 beta-estradiol (E2) and progesterone (P4) in ovarian GCs (p < 0.01). Further studies found that BMP6 inhibited the mRNA expression of 3β-HSD and steroid synthesis acute regulator (StAR) but significantly promoted the mRNA expression of the E2 synthesis rate-limiting enzyme CYP19A1 and the P4 synthesis rate-limiting enzyme CYP11A1 (p < 0.01). Taken together, these results showed that the exogenous addition of BMP6 did not affect the proliferation, cell cycle, and apoptosis of goat ovarian GCs but promoted the secretion of E2 and progesterone P4 in ovarian GCs by upregulating the mRNA expressions of CYP19A1 and CYP11A1. Full article

Mammalian sex hormones are steroid-structured compounds that support the growth and development of plants at low concentrations. Since they affect the physiological processes in plants, it has been thought that mammalian sex hormones may cause modifications to plant genomes and epigenetics. This study aims to determine whether different mammalian sex hormones (17 β-estradiol, estrogen, progesterone, and testosterone) in several concentrations (0, 10⁻⁴, 10⁻⁶, and 10⁻⁸ mM) affect genetic or epigenetic levels in bean plants, using in vitro tissue cultures from plumule explants. We investigated levels of DNA damage, changes in DNA methylation and DNA stability in common bean exposed to mammalian sex hormones (MSH) using inter-primer binding site (iPBS) and Coupled Restriction Enzyme Digestion-iPBS (CRED-iPBS) assays, respectively. The highest rate of polymorphism in iPBS profiles was observed when 10⁻⁴ mM of estrogen (52.2%) hormone was administered. This finding indicates that genetic stability is reduced. In the CRED-iPBS profile, which reveals the methylation level associated with the DNA cytosine nucleotide, 10⁻⁴ mM of estrogen hormone exhibited the highest hypermethylation value. Polymorphism was observed in all hormone administrations compared to the control (without hormone), and it was determined that genomic stability was decreased at high concentrations. Taken together, the results indicate that 17 β-estradiol, estrogen, progesterone, and testosterone in bean plants affect genomic instability and cause epigenetic modifications, which is an important control mechanism in gene expression. Full article

Endocrine disrupting compounds (EDCs) in the environment are considered a motif of concern, due to the widespread occurrence and potential adverse ecological and human health effects. The natural estrogen, 17β-estradiol (E2), is frequently detected in receiving water bodies after not being efficiently removed in conventional wastewater treatment plants (WWTPs), promoting a negative impact for both the aquatic ecosystem and human health. In this study, the biodegradation of E2 by Rhodococcus sp. ED55, a bacterial strain isolated from sediments of a discharge point of WWTP in Coloane, Macau, was investigated. Rhodococcus sp. ED55 was able to completely degrade 5 mg/L of E2 in 4 h in a synthetic medium. A similar degradation pattern was observed when the bacterial strain was used in wastewater collected from a WWTP, where a significant improvement in the degradation of the compound occurred. The detection and identification of 17 metabolites was achieved by means of UPLC/ESI/HRMS, which proposed a degradation pathway of E2. The acute test with luminescent marine bacterium Aliivibrio fischeri revealed the elimination of the toxicity of the treated effluent and the standardized yeast estrogenic (S-YES) assay with the recombinant strain of Saccharomyces cerevisiae revealed a decrease in the estrogenic activity of wastewater samples after biodegradation. Full article

Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells (cholangiocytes) and primarily affects postmenopausal women, when their estrogen levels sharply decrease. An impaired cholangiocyte response to estrogen characterizes the terminal stage of the disease, as this is when an inefficiency of cholangiocyte proliferation, in balancing the loss of intrahepatic bile ducts, is observed. Here, we report that the estrogen precursor dehydroepiandrosterone (DHEA) and its sulfate metabolites, DHEA-S and 17 β-estradiol, enhance the proliferation of cholangiocytes and hepatocytes in vitro. Flow cytometry analysis showed that DHEA and DHEA-S decreased glyco-chenodeoxycholic acid (GCDC)-driven apoptosis in cholangiocytes. Cell viability assay (MTT) indicated that ER-α, -β, and the G-protein-coupled estrogen receptor, are involved in the protection of DHEA against oxidative stress in cholangiocytes. Finally, immunoblot analysis showed an elevated level of steroid sulfatase and a reduced level of sulfotransferase 1E1 enzymes, involved in the desulfation/sulfation process of estrogens in cirrhotic PBC, and primary sclerosis cholangitis (PSC) liver tissues, another type of chronic cholestatic and immune-mediated liver disease. Taken together, these results suggest that DHEA can prevent the deleterious effects of certain potentially toxic bile acids and reactive oxygen species, delaying the onset of liver disease. Full article

Several chondrichthyan species are threatened, and we must increase our knowledge of their reproductive biology in order to establish assisted reproductive protocols for ex situ or in situ endangered species. The small-spotted catshark (Scyliorhinus canicula) is one of the most abundant shark species of the Mediterranean coast and is easy to maintain in aquaria; therefore, it is considered an ideal reproductive model. This study aimed to compare S. canicula male reproductive function in aquarium-housed (n = 7) and wild-captured animals, recently dead (n = 17). Aquarium-housed animals had lower semen volume (p = 0.005) and total sperm number (p = 0.006) than wild-captured animals, but similar sperm concentrations. In terms of sperm parameters, aquarium-housed sharks showed higher total sperm motility (p = 0.004), but no differences were observed regarding sperm viability, mitochondrial membrane potential, or membrane integrity. A morphometric study pointed to a significantly longer head (p = 0.005) and acrosome (p = 0.001) in wild-captured animals. The results of the spermatozoa morphological study of S. canicula were consistent with previous results obtained in other chondrichthyan species. With regard to sex hormones, testosterone levels were significantly lower in aquarium-housed animals (p ≤ 0.001), while similar levels of 17β-estradiol and progesterone were found. In short, the present study provides evidence of good in vitro semen quality in S. canicula housed in an aquarium, underlining their excellent potential for application in reproductive technologies for this and other chondrichthyan species. Full article

Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate with a much higher stiffness than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting a sex-disaggregated analysis of changes in cellular morphology and relative levels of profibrotic signaling proteins in CFs cultured on 8 kPa stiffness plates with and without 17 β-estradiol (E2). Cyclic immunofluorescent analysis indicated that there was a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs occur at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein–protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored sex-informed prevention and treatment interventions of cardiac fibrosis. Full article

In addition to the well-known central modulatory role of orexins, we recently demonstrated a peripheral involvement in swine granulosa cells for orexin A and in adipose tissue for orexin B (OXB). The aim of present research was to verify immunolocalization of OXB and its potential role in modulating the main features of swine granulosa cells. In particular, we explored the effects on granulosa cell proliferation (through the incorporation of bromodeoxyuridine), cell metabolic activity (as indirect evaluation by the assessment of ATP), steroidogenic activity (by immunoenzymatic examination) and redox status (evaluating the production of superoxide anion by means of the WST test, production of nitric oxide through the use of the Griess test and the non-enzymatic reducing power by FRAP test). Our data point out that OXB does not modify granulosa cell growth, steroidogenesis and superoxide anion generation. On the contrary, the peptide stimulates (p < 0.05) nitric oxide output and non-enzymatic reducing power. Since new vessel growth is crucial for ovarian follicle development, a further aim of this study was to explore the expression of prepro-orexin and the effects of OXB on swine aortic endothelial cells. We found that the peptide is ineffective in modulating cell growth, while it inhibits redox status parameters. In addition, we demonstrated a stimulatory effect on angiogenesis evaluated in fibrin gel angiogenesis assay. Taken together, OXB appears to be potentially involved in the modulation of redox status in granulosa and endothelial cells and we could argue an involvement of the peptide in the follicular angiogenic events. Full article

Premature ovarian insufficiency (POI) is a type of hypergonadotropic hypogonadism caused by impaired ovarian function before the age of 40. Due to the hypoestrogenism, women with POI experience a variety of health complications, including an increased risk of bone mineral density loss and developing osteopenia and osteoporosis, which poses an important problem for public health. Purpose: The aim of this study was to evaluate and compare the values of bone mineral density (BMD), T-score and Z-score within the lumbar spine (L1-L4) using the dual energy X-ray absorptiometry method. The dual-energy X-ray absorptiometry (DXA) scans described in this original prospective article were performed at the time of POI diagnosis and after treatment with sequential hormone replacement therapy (HRT). Materials and methods: This study included 132 patients with a mean age of 31.86 ± 7.75 years who had been diagnosed with idiopathic POI. The control group consisted of 17 healthy women with regular menstrual cycles, with a mean age of 23.21 ± 5.86 years. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), insulin, and fasting serum glucose were measured. Lumbar spine (L1-L4) BMD was assessed by means of dual-energy X-ray absorptiometry. DXA scans were performed at the time of diagnosis and following treatment with sequential hormone replacement therapy (HRT) comprised of daily oral 2 mg 17-β-estradiol and 10 mg dydrogesterone. The mean time of observation was 3 ± 2 years. Results: Patients in the POI group presented with characteristic hypergonadotropic hypogonadism. They had a significantly decreased mean lumbar spine BMD when compared to healthy controls (1.088 ± 0.14 g/cm²) vs. 1.150 ± 0.30 g/cm²) (p = 0.04) as well as a decreased T-score (0.75 ± 1.167 vs. −0.144 ± 0.82) (p = 003). There was a significant increase in BMD (1.088 ± 0.14 vs. 1.109 ± 0.14; p < 0.001), T-score (−0.75 ± 1.17 vs. −0.59 ± 1.22; p < 0.001), and Z-score (−0.75 ± 1.12 vs. −0.49 ± 1.11; p < 0.001) after the implementation of HRT when compared to pre-treatment results. Conclusions: In conclusion, this study has demonstrated that patients with POI often have decreased bone mineral density and that the implementation of HRT has a significant and positive influence on bone mass. The implementation of full-dose HRT and monitoring of bone status is particularly important in these patients. Full article