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Molecules (Basel, Switzerland) Oct 2022Molecularly imprinted polymers@ethylenediamine-modified carbon dots grafted on cotton fabrics (MIPs@EDA-CDs/CF) and smartphone-based fluorescence image analysis were...
Molecularly imprinted polymers@ethylenediamine-modified carbon dots grafted on cotton fabrics (MIPs@EDA-CDs/CF) and smartphone-based fluorescence image analysis were proposed and used for the first time for the detection of 17 α-methyltestosterone (MT). The EDA-CDs were synthesized and grafted on cotton fabric before coating with the MIPs. The MIPs were synthesized using the MT as a template molecule, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, and azobisisobutyronitrile (AIBN) as an initiator. The MIPs@EDA-CDs/CF were characterized using FTIR, SEM-EDS, and RGB fluorescence imaging. The fluorescence images were also taken using a smartphone and the ImageJ program was used for RGB measurement. The Δ red intensity was linearly proportional to MT concentration in the range of 100 to 1000 μg/L (R = 0.999) with a detection limit of 44.4 μg/L and quantification limit of 134 μg/L. The MIPs@EDA-CDs/CF could be stored at 4 °C for a few weeks and could be reused twice. The proposed method could apply for the specific determination of MT in water and sediment samples along with satisfactory recoveries of 96-104% and an acceptable relative standard deviation of 1-6% at the ppb level.
Topics: Molecular Imprinting; Carbon; Molecularly Imprinted Polymers; Methyltestosterone; Polymers
PubMed: 36364082
DOI: 10.3390/molecules27217257 -
International Journal of Molecular... Sep 2018In this study, we systematically investigated the process of sex reversal induced by 17-methyltestosterone (MT) feeding and MT-feeding withdrawal at the ovary...
In this study, we systematically investigated the process of sex reversal induced by 17-methyltestosterone (MT) feeding and MT-feeding withdrawal at the ovary differentiation stage in orange-spotted groupers, . Gonadal histology showed that MT feeding induced a precocious sex reversal from immature ovaries to testes, bypassing the formation of an ovarian cavity, and MT-feeding withdrawal led to an ovarian fate. In both the MT feeding and MT-feeding withdrawal phases, cytochrome P450 family 11 subfamily B () gene expression and serum 11-KT levels were not significantly changed, suggesting that the MT-treated fish did not generate endogenous steroids, even though active spermatogenesis occurred. Finally, by tracing doublesex-expressing and Mab-3-related transcription factor 1 (dmrt1)-expressing cells and TUNEL (terminal deoxynucleotidyl transferase 2-deoxyuridine, 5-triphosphate nick end labeling) assays, we found that the efferent duct formed first, and then, the germ cells and somatic cells of the testicular tissue were generated around the efferent duct during MT-feeding-induced precocious sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex reversal induced by exogenous hormones during sex differentiation in the protogynous orange-spotted grouper.
Topics: Animals; Bass; Cytochrome P450 Family 11; Female; Fish Proteins; Germ Cells; Male; Methyltestosterone; Sex Determination Processes; Sex Differentiation; Transcription Factors
PubMed: 30235790
DOI: 10.3390/ijms19092828 -
General and Comparative Endocrinology May 2023The division of the brain manifests in lateralized physical behaviors, where specific tasks originate from one side of the body. Previous studies have shown that birds...
The division of the brain manifests in lateralized physical behaviors, where specific tasks originate from one side of the body. Previous studies have shown that birds and reptiles mediate aggression in their right hemisphere and focus on opponents with their left eye. Degree of lateralization varies between sexes, likely due to androgen inhibition of lateralization in mammals, birds, and fish, but remains untested in herpetofauna. In this experiment, we investigated the effect of androgen exposure on cerebral lateralization in the American Alligator, Alligator mississippiensis. Alligator eggs were collected and incubated at female producing temperature with a subset dosed with methyltestosterone in ovo. Dosed hatchlings were randomly paired with control individuals and their interactions were recorded. The number of bites initiated by focus from each eye and the number of times an animal was bitten on each side of the body was recorded for each individual to elucidate cerebral lateralization in aggression. Control alligators had a significant bias towards left-eye bite initiation whereas androgen exposed alligators used both eyes indiscriminately. No significance was found in injury patterns. This study suggests that androgen exposure inhibits cerebral lateralization in alligator brains and corroborates right-hemisphere mediation of aggression, something previously unstudied in crocodilians.
Topics: Animals; Female; Alligators and Crocodiles; Androgens; Eggs; Mammals; Methyltestosterone; Temperature
PubMed: 36848983
DOI: 10.1016/j.ygcen.2023.114248 -
Frontiers in Genetics 202117α-Methyltestosterone (MT) is a synthetic androgen. The objective of this study was to explore the effects of exogenous MT on the growth and gonadal development of...
17α-Methyltestosterone (MT) is a synthetic androgen. The objective of this study was to explore the effects of exogenous MT on the growth and gonadal development of female rare minnow Female groups were exposed to 25-100 ng/L of MT for 7 days. After exposure for 7 days, the total weight and body length were significantly decreased in the 50-ng/L MT groups. The major oocytes in the ovaries of the control group were vitellogenic oocytes (Voc) and cortical alveolus stage oocytes (Coc). In the MT exposure groups, some fish had mature ovaries with a relatively lower proportion of mature oocytes, and the diameter of the perinucleolar oocytes (Poc) was decreased compared with those of the control group. Ovarian VTG, FSH, LH, 11-KT, E2, and T were significantly increased after exposure to 50 ng/L of MT for 7 days. Unigenes (73,449), 24 known mature microRNAs (miRNAs), and 897 novel miRNAs in the gonads of were found using high-throughput sequencing. Six mature miRNAs (miR-19, miR-183, miR-203, miR-204, miR-205, and miR-96) as well as six differentially expressed genes (, , , , , and ) that may be associated with ovarian development and innate immune response were assayed using qPCR. Furthermore, the miR-183 cluster and miR-203 were differentially expressed in MT-exposed ovaries of the different groups. This study provides some information about the role of miRNA-mRNA pairs in the regulation of ovarian development and innate immune system, which will facilitate future studies of the miRNA-RNA-associated regulation of teleost reproduction.
PubMed: 34421998
DOI: 10.3389/fgene.2021.695699 -
Genetics and Molecular Research : GMR Sep 2013The synthetic hormone, 17-α-methyltestosterone (MT), is used in fish hatcheries to induce male monosex. Androgenic effects on various fish species have been reported;...
The synthetic hormone, 17-α-methyltestosterone (MT), is used in fish hatcheries to induce male monosex. Androgenic effects on various fish species have been reported; however, few studies have assessed possible genotoxic effects, although there are concerns about such effects in target and non-target species. We evaluated genotoxic and gonadal effects of MT in adult tilapia (Oreochromis niloticus) and Astyanax bimaculatus (a common native non-target fish in Brazil). Fish were fed for 28 days with ration containing MT (60 mg/L), a normal dose used in fish farming. Evaluation of MT genotoxicity was carried out through micronucleus test, nuclear abnormality, and comet assay analyses on peripheral erythrocyte cells collected by cardiac puncture. There were no significant differences in micronucleus frequencies and DNA damage in both species; however, MT caused cytogenetic toxicity in the non-target species, A. bimaculatus, with significantly increased erythrocyte nuclear abnormalities. Histopathological analyses of the female gonads of O. niloticus revealed that MT significantly inhibited the development of mature oocytes, while in A. bimaculatus it provoked significant inhibition of spermatozoa production. We concluded that discharge of fish-hatcheries water onto the surface of aquatic ecosystems should be avoided due to risks to reproduction of native species.
Topics: Animals; Brazil; Characidae; Cichlids; Comet Assay; DNA Damage; Female; Gonads; Male; Methyltestosterone; Micronucleus Tests; Reproduction; Spermatozoa
PubMed: 24085447
DOI: 10.4238/2013.September.23.4 -
Ecotoxicology and Environmental Safety Jan 2023Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the...
Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.
Topics: Animals; Biomarkers; Embryo, Nonmammalian; Endocrine Disruptors; Endocrine System; Estrogens; Gene Expression; Phosphatidate Phosphatase; Water Pollutants, Chemical; Zebrafish
PubMed: 36608563
DOI: 10.1016/j.ecoenv.2023.114514 -
Integrative and Comparative Biology Dec 2012Interest in the occurrence and fate of trace organic contaminants in the aquatic environment and their potential effects on all organisms has increased over the past two...
Interest in the occurrence and fate of trace organic contaminants in the aquatic environment and their potential effects on all organisms has increased over the past two decades. Researches on contaminants have included both natural and synthetic estrogenic contaminants, neuroactive pharmaceuticals, and other endocrine disrupting chemicals that are mediated by the androgen and progesterone receptors. Exposure to very low concentrations (ng/L or parts per trillion) of compounds such as 17α-ethynylestradiol (EE(2)), a synthetic estrogen, can affect gonadal development, viability and production of eggs, fertilization rate, and sexual differentiation in fishes. Researchers and aquaculturists have used exposures to relatively higher concentrations of androgens and estrogens, for example 17α-methyltestosterone and EE(2), respectively, to direct sexual differentiation in a number of fishes. Rivulus is an androdioecious teleost that in nature exists mostly as selfing, simultaneous hermaphrodites as well as a small number of males that outcross with hermaphrodites. No one has either collected females in the wild or created functional females in the laboratory. This study had two goals: (1) to develop a reliable protocol to produce female rivulus to enable downstream technologies such as embryo injections and (2) to investigate developmental effects of EE(2) on the sexual outcome, reproductive health, and relevant gene expression in rivulus. With these goals in mind, we exposed newly hatched rivulus to nominal concentrations of 0.1, 0.5, or 1.0 parts per million (ppm) EE(2) for 4 weeks, grew them to maturity in control water, and then compared egg production; production and viability of embryos; age of reproductive maturity; and gene expression in the brain, gonad, and liver. Expression levels of seven genes with known relevance to gonadal development and function (cyp19a1b, cyp19a1a, dmrt1, figα, ERα, ERβ, and vtg) were measured using quantitative polymerase chain reaction (PCR). There was a significant decrease in cyp19a1a gene expression in the brain, corresponding to increased exposure to EE(2). Gonadal gene expression for cyp19a1a, ERα, and dmrt1 also decreased in response to EE(2). Vtg expression in the liver was unaffected. Our hypothesis that exposure to EE(2) during gonadal differentiation would direct female development was not supported by the data. However, treated fish exhibited impaired reproductive health that included reduced expression of relevant genes and, importantly, decreased fertility, increased sterility, and delay of age of reproductive maturity. The results of this study suggest that the development and maintenance of a simultaneous hermphrodite ovotestis may be particularly sensitive to its hormonal milieu.
Topics: Animals; Cloning, Molecular; Cyprinodontiformes; DNA, Complementary; Developmental Biology; Ethinyl Estradiol; Female; Gene Expression Regulation, Developmental; Hermaphroditic Organisms; Male; Real-Time Polymerase Chain Reaction; Sexual Development; Transcriptome
PubMed: 22927136
DOI: 10.1093/icb/ics110 -
Molecules (Basel, Switzerland) Mar 2020Novel reduction-responsive hyaluronic acid-chitosan-lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast cancer by...
Novel reduction-responsive hyaluronic acid-chitosan-lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast cancer by targeting Cluster of Differentiation 44 (CD44)-overexpressing cells and reduction-triggered 17α-Methyltestosterone (MT) release for systemic delivery. The effectiveness of these nanoparticles was investigated by different assays, including release rate, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), lactate dehydrogenase (LDH), caspase-3 activity, Rhodamine 123 (RH-123), and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro experiments revealed that Methyltestosterone/Hyaluronic acid-chitosan-lipoic acid nanoparticles (MT/HACSLA-NPs) illustrated a sustained drug release in the absence of glutathione (GSH), while the presence of GSH led to fast MT release. HACSLA-NPs also showed high cellular internalization via CD44 receptors, quick drug release inside the cells, and amended cytotoxicity against positive CD44 BT-20 breast cancer cell line as opposed to negative CD44, Michigan Cancer Foundation-7 (MCF-7) cell line. These findings supported that these novel reduction-responsive NPs can be promising candidates for efficient targeted delivery of therapeutics in cancer therapy.
Topics: Antineoplastic Agents, Hormonal; Biomarkers; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Female; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Methyltestosterone; Nanoparticles; Oxidation-Reduction; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 32151062
DOI: 10.3390/molecules25051181 -
Breast Cancer Research : BCR 2000The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones... (Review)
Review
The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities.
Topics: Breast; Breast Neoplasms; Clinical Trials as Topic; Endometrium; Epithelial Cells; Estrogen Replacement Therapy; Estrogens; Feasibility Studies; Female; Forecasting; Gonadotropin-Releasing Hormone; Goserelin; Humans; Incidence; Mammography; Methyltestosterone; Multicenter Studies as Topic; Neoplasms, Second Primary; Osteoporosis; Ovariectomy; Ovary; Pilot Projects; Premenopause; Progesterone; Progestins; Risk; Secretory Rate
PubMed: 11250719
DOI: 10.1186/bcr67 -
International Journal of Molecular... Aug 2019A-type K channels contribute to regulating the propagation and frequency of action potentials in smooth muscle cells (SMCs). The present study (i) identified the...
A-type K channels contribute to regulating the propagation and frequency of action potentials in smooth muscle cells (SMCs). The present study (i) identified the molecular components of A-type K channels in rat vas deferens SMs (VDSMs) and (ii) showed the long-term, genomic effects of testosterone on their expression in VDSMs. Transcripts of the A-type K channel α subunit, Kv4.3L and its regulatory β subunits, KChIP3, NCS1, and DPP6-S were predominantly expressed in rat VDSMs over the other related subtypes (Kv4.2, KChIP1, KChIP2, KChIP4, and DPP10). A-type K current (I) density in VDSM cells (VDSMCs) was decreased by castration without changes in I kinetics, and decreased I density was compensated for by an oral treatment with 17α-methyltestosterone (MET). Correspondingly, in the VDSMs of castrated rats, Kv4.3L and KChIP3 were down-regulated at both the transcript and protein expression levels. Changes in Kv4.3L and KChIP3 expression levels were compensated for by the treatment with MET. These results suggest that testosterone level changes in testosterone disorders and growth processes control the functional expression of A-type K channels in VDSMCs.
Topics: Animals; Blotting, Western; Castration; Down-Regulation; Electrophysiology; Kv Channel-Interacting Proteins; Male; Methyltestosterone; Muscle, Smooth; Rats; Rats, Wistar; Testosterone; Vas Deferens
PubMed: 31438481
DOI: 10.3390/ijms20174073