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Fish & Shellfish Immunology Aug 2022The development and intensification of tilapia farming depends on the manipulation of some physiological functions, such as the sexual inversion of larvae using a...
The development and intensification of tilapia farming depends on the manipulation of some physiological functions, such as the sexual inversion of larvae using a synthetic androgen (17α-methyltestosterone). This inversion, however, may represent a potential oxidative stress factor and cause damage to animals in the short, medium, and long term. Dietary supplementation of natural antioxidant compounds is an interesting alternative to combat such damage. To test this hypothesis, an experimental trial was carried out involving sexual inverted and non-inverted Nile tilapia fingerlings, both supplemented and not supplemented with a blend of organic acids and essential oils protected by microencapsulation. Animals were divided into four experimental groups: NI (non-inverted animals), I (sexual inverted animals), NI + M (non-inverted animals supplemented with microcapsules), and I + M (sexual inverted animals supplemented with microcapsules). Blood parameters (WBC - white blood cells; LY - lymphocytes; RBC - red blood cells; HGB - hemoglobin; HCT - hematocrit number; MCH - mean corpuscular hemoglobin; MCV - mean corpuscular volume and MCHC - mean corpuscular hemoglobin concentration), as well as oxidative stress markers (enzymatic activity of superoxide dismutase - SOD and catalase - CAT; and total antioxidant capacity - 2,2-diphenyl-1-picryl-hydrazyl (DPPH)) and gene expression (heat shock protein 70 kDa - HSP70) were evaluated. The HGB (p < 0.001) and HCT (p = 0.005) parameters were reduced beyond the recommended limits for the animals in group I. The MCV varied statistically between the groups (p < 0.001). However, all values were within the recommended range for the species, jointly indicating normocytic anemia in group I fingerlings at the time of collection. The activity of CAT and SOD, as well as DPPH differed statistically between the experimental groups (p < 0.001), with the lowest SOD and CAT activity, as well as the highest DPPH registered in animals supplemented with microcapsules. The expression of HSP70 was lower in I + MI animals (p < 0.001). The synergistic evaluation of the results indicates that animals sexual inverted during the larval stage have a lower total antioxidant capacity in the fingerling stage, which reflects a worsening in hematological and enzymatic parameters related to immunity; and that dietary supplementation with blend of organic acids and essential oils protected by microencapsulation is sufficient to improve the immunological response both in sexual inverted and non-inverted fingerlings.
Topics: Animals; Animal Feed; Antioxidants; Capsules; Cichlids; Diet; Dietary Supplements; Immunity; Oils, Volatile; Superoxide Dismutase
PubMed: 35863539
DOI: 10.1016/j.fsi.2022.07.023 -
Clinical and Experimental Reproductive... Jun 2024The aim of this study was to compare the outcomes of in vitro fertilization (IVF) in patients with a poor ovarian response who used methyltestosterone, versus those...
OBJECTIVE
The aim of this study was to compare the outcomes of in vitro fertilization (IVF) in patients with a poor ovarian response who used methyltestosterone, versus those using a placebo, in an infertility clinic setting.
METHODS
This clinical trial included 120 women who had undergone IVF with intracytoplasmic sperm injection due to poor ovarian reserve and infertility. The study took place at the Yas Infertility Center in Tehran, Iran, between January 1, 2018 and January 1, 2019. In the intervention group, 25 mg of methyltestosterone was administered daily for 2 months prior to the initiation of assisted reproductive treatment. The control group was given placebo tablets for the same duration before starting their cycle. Each group was randomly assigned 60 patients. All analyses were performed using SPSS ver. 23 (IBM Corp.).
RESULTS
The endometrial thickness in the intervention group was 7.57±1.22 mm, whereas in the control group, it was 7.11±1.02 (
p =0.028). The gonadotropin number was significantly higher in the control group (64.7±13.48 vs. 57.9±9.25,p =0.001). However, there was no significant difference between the two groups in the antral follicular count. The chemical and clinical pregnancy rates in the intervention group were 18.33% and 15% respectively, compared to 8.33% and 6.67% in the control group. The rate of definitive pregnancy was marginally higher in the intervention group (13.3% vs. 3.3%, p=0.05).CONCLUSION
The findings of this study suggest that pretreatment with methyltestosterone significantly increases endometrium thickness and is associated with an increase in the definitive pregnancy rate.
PubMed: 38812245
DOI: 10.5653/cerm.2023.05946 -
Biology Jul 2022Chinese soft-shelled turtles display obvious sex dimorphism. The exogenous application of hormones (estradiol and methyltestosterone) can change the direction of gonadal...
Chinese soft-shelled turtles display obvious sex dimorphism. The exogenous application of hormones (estradiol and methyltestosterone) can change the direction of gonadal differentiation of to produce sex reversed individuals. However, the molecular mechanism remains unclear. In this study, TMT-based quantitative proteomics analysis of four types of (female, male, pseudo-female, and pseudo-male) gonads were compared. Quantitative analysis of 6107 labeled proteins in the four types of gonads was performed. We identified 440 downregulated and 423 upregulated proteins between pseudo-females and males, as well as 394 downregulated and 959 upregulated proteins between pseudo-males and females. In the two comparisons, the differentially expressed proteins, including K7FKG1, K7GIQ2, COL4A6, K7F2U2, and K7FF80, were enriched in some important pathways, such as focal adhesion, endocytosis, apoptosis, extracellular matrix-receptor interaction, and the regulation of actin cytoskeleton, which were upregulated in pseudo-female vs. male and downregulated in pseudo-male vs. female. In pathways such as ribosome and spliceosome, the levels of RPL28, SRSF3, SNRNP40, and HNRNPK were increased from male to pseudo-female, while they decreased from female to pseudo-male. All differentially expressed proteins after sexual reversal were divided into six clusters, according to their altered levels in the four types of , and associated with cellular processes, such as embryonic development and catabolic process, that were closely related to sexual reversal. These data will provide clues for the sexual reversal mechanism in .
PubMed: 36101459
DOI: 10.3390/biology11071081 -
The Journal of Steroid Biochemistry and... Mar 2024In comparison to well-known drug-metabolizing organs such as the liver, the metabolic capacity of human skin is still not well elucidated despite the widespread use of...
In comparison to well-known drug-metabolizing organs such as the liver, the metabolic capacity of human skin is still not well elucidated despite the widespread use of topical drug application. To gain a comprehensive insight into anabolic steroid metabolism in the skin, six structurally related anabolic androgenic steroids, testosterone, metandienone, methyltestosterone, clostebol, dehydrochloromethyltestosterone, and methylclostebol, were applied to human keratinocytes and fibroblasts derived from the juvenile foreskin. Phase I metabolites obtained from incubation media were analyzed by gas chromatography-mass spectrometry. The 5α-reductase activity was predominant in the metabolic pathways as supported by the detection of 5α-reduced metabolites after incubation of testosterone, methyltestosterone, clostebol, and methylclostebol. Additionally, the stereochemistry structures of fully reduced metabolites (4α,5α-isomers) of clostebol and methylclostebol were newly confirmed in this study by the help of inhouse synthesized reference materials. The results provide insights into the steroid metabolism in human skin cells with respect to the characteristics of the chemical structures.
Topics: Humans; Methyltestosterone; Anabolic Androgenic Steroids; Anabolic Agents; Testosterone Congeners; Testosterone; Biotransformation; Doping in Sports
PubMed: 38092130
DOI: 10.1016/j.jsbmb.2023.106444 -
Genes Sep 2022Nile tilapia is a GSD + TE (Genetic Sex Determination + Temperature Effect) fish, and high-temperature treatment during critical thermosensitive periods (TSP) can induce...
Nile tilapia is a GSD + TE (Genetic Sex Determination + Temperature Effect) fish, and high-temperature treatment during critical thermosensitive periods (TSP) can induce the sex reversal of Nile tilapia genetic females, and brain transcriptomes have revealed the upregulation of (Jumonji and AT-rich domain containing 2) expression after 36 °C high-temperature treatment for 12 days during TSP. It was shown that JARID2 forms a complex with polycomb repressive complex 2 (PRC2) that catalyzed H3K27me3, which was strongly associated with transcriptional repression. In this study, was cloned and characterized in Nile tilapia, which was highly conserved among the analyzed fish species. The expression of was upregulated in the gonad of 21 dpf XX genetic females after 12-day high-temperature treatment and reached a similar level to that of males. Similar responses to high-temperature treatment also appeared in the brain, heart, liver, muscle, eye, and skin tissues. Interestingly, expression was only in response to high-temperature treatment, and not to 17α-methyltestosterone (MT) or letrozole treatments; although, these treatments can also induce the sex reversal of genetic Nile tilapia females. Further studies revealed that responded rapidly at the 8th hour after high-temperature treatment. Considering that JARID2 can recruit PRC2 and establish H3K27me3, we speculated that it might be an upstream gene participating in the regulation of Nile tilapia GSD + TE through regulating the H3K27 methylation level at the locus of many sex differentiation-related genes.
Topics: Animals; Male; Female; Cichlids; Temperature; Methyltestosterone; Letrozole; Histones; Cloning, Molecular; Polycomb Repressive Complex 2
PubMed: 36292604
DOI: 10.3390/genes13101719 -
Angewandte Chemie (International Ed. in... Jul 2020To gain insight into the host functions of a nanocavity encircled by both polyaromatic panels and heteroatoms, nitrogen-doped polyaromatic capsules were successfully...
To gain insight into the host functions of a nanocavity encircled by both polyaromatic panels and heteroatoms, nitrogen-doped polyaromatic capsules were successfully synthesized from metal ions and pyridine-embedded, bent anthracene-based ligands. The new capsules display unique host-guest interactions in the isolated cavities, which are distinct from those of the undoped analogues. Besides the inclusion of Ag ions, the large absorption change of fullerene C and altered emission of a BODIPY dimer are observed upon encapsulation by the present hosts. Moreover, the N-doped capsule exhibits specific binding ability toward progesterone and methyltestosterone, known as a natural female and synthetic male hormone, respectively, in water.
PubMed: 32291946
DOI: 10.1002/anie.202004168 -
Frontiers in Cell and Developmental... 2022Sex dimorphism is a key feature of Chinese soft-shelled turtle (). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth....
Sex dimorphism is a key feature of Chinese soft-shelled turtle (). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth. Exogenous hormones like estradiol and methyltestosterone can induce sexual reversal to form new phenotypes (pseudo-female, PF; pseudo-male, PM) without changing the genotype. The possibility of inducing sexual reversal is particularly important in aquaculture breeding, but the underlying biological mechanisms remain unclear. Here we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in . Nanopore sequencing of the four gender types (M, F, PF, and PM) showed that the distribution of read length and gene expression was more similar between same-sex phenotypes than same-sex genotypes. Compared to turtles with an M phenotype, alternative splicing was more pronounced in F turtles, especially at alternative 3' splice sites, alternative 5' splice sites, and alternative first exons. Furthermore, the two RNA methylation modifications m5C and m6A were differentially distributed across gender phenotypes, with the M type having more modification sites in coding sequence regions, but fewer modification sites in 3'UTR regions. Quantitative analysis of enriched m6A RNAs revealed that the N6-methylated levels of , , and were significantly higher in M phenotype individuals, while the N6-methylated levels of were reduced after sexual reversal from both M and F phenotypes. Taken together, these findings reveal an important role of epigenetics during sexual reversal in Chinese soft-shelled turtles.
PubMed: 35399508
DOI: 10.3389/fcell.2022.876045 -
Biochemical and Biophysical Research... Apr 2023In pharmacokinetics plasma protein binding (PPB) is a well-established parameter impacting drug disposition. The unbound fraction (f) is arguably regarded the effective...
In pharmacokinetics plasma protein binding (PPB) is a well-established parameter impacting drug disposition. The unbound fraction (f) is arguably regarded the effective concentration at the target site. Pharmacology and toxicology, increasingly use in vitro models. The translation of in vitro concentrations to in vivo doses can be supported by toxicokinetic modelling, e.g. physiologically based toxicokinetic models (PBTK). PPB of a test substance is an input parameter for PBTK. We compared three methods to quantify f: rapid equilibrium dialysis (RED), ultrafiltration (UF) and ultracentrifugation (UC) using twelve substances covering a wide range of Log P (-0.1 to 6.8) and molecular weights (151 and 531 g/mol): Acetaminophen, Bisphenol A, Caffeine, Colchicine, Fenarimol, Flutamide, Genistein, Ketoconazole, α-Methyltestosterone, Tamoxifen, Trenbolone and Warfarin. After RED and UF separation, three polar substances (Log P < 2) were largely unbound (f > 70%), while more lipophilic substances were largely bound (f < 33%). Compared to RED or UF, UC resulted in a generally higher f of lipophilic substances. f obtained after RED and UF were more consistent with published data. For half of the substances, UC resulted in f higher than the reference data. UF, RED and both UF and UC, resulted in lower f of Flutamide, Ketoconazole and Colchicine, respectively. For f quantifications, the separation method should be selected according to the test substance's properties. Based on our data, RED is suitable for a broader range of substances while UC and UF are suitable for polar substances.
Topics: Ultrafiltration; Flutamide; Ketoconazole; Renal Dialysis; Protein Binding; Blood Proteins; Ultracentrifugation
PubMed: 36812744
DOI: 10.1016/j.bbrc.2023.02.021 -
Biology Apr 202217α-Methyltestosterone (MT) is a synthetic steroid that has been widely used to masculinize many fish species when administered early during larval development,...
17α-Methyltestosterone (MT) is a synthetic steroid that has been widely used to masculinize many fish species when administered early during larval development, however, reports on its efficacy on adults is limited. To this end, this study investigated the efficacy of MT in the masculinization of the eastern mosquitofish () at two adult stages (maiden and repeat gravid females). The treated females were fed control or respective MT incorporated feed (0-200 mg/kg diet) for 50 days. Effects of the hormone on secondary sexual characteristics, internal gonad morphology, expression of the Anti-Müllerian Hormone () gene and sexual behavior of the treated females were investigated. The results showed that MT at the dose of 50 mg/kg feed stimulated secondary sexual character development, upregulated expression of , formation of testicular tissue and a shift in the behavior similar to those of normal males, prominently so in treated maiden gravid females. Post-treatment, long-term observations indicated that only two masculinized females reverted back to being females and gave birth to young. Induction of masculinizing effects in most individuals suggests that the sexual phenotype of this species appears to be highly plastic with potential to sex reverse at adulthood. This in combination with its small size and short reproductive cycle could provide an ideal system to explore the mechanisms of sequential hermaphroditism in fish and contribute to genetic control of this pest fish.
PubMed: 35625423
DOI: 10.3390/biology11050694 -
Journal of Investigative Medicine High... 2022A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy... (Review)
Review
A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.
Topics: Adult; Breast Neoplasms; COVID-19; COVID-19 Vaccines; Female; Gender Identity; Humans; Male; Mastectomy; Sarcoidosis; Uveitis; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35313760
DOI: 10.1177/23247096221086450