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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 -
International Journal of Biological... Jan 2024A feature of the Chinese soft-shelled turtle (Pelodiscus sinensis) is seasonal spermatogenesis; however, the underlying molecular mechanism is not well clarified. Here,...
A feature of the Chinese soft-shelled turtle (Pelodiscus sinensis) is seasonal spermatogenesis; however, the underlying molecular mechanism is not well clarified. Here, we firstly cloned and characterized P. sinensis DKKL1, and then performed comparative genomic studies, expression analysis, and functional validation. P. sinensis DKKL1 had 2 putative N-glycosylation sites and 16 phosphorylation sites. DKKL1 also had classic transmembrane structures that were extracellularly localized. DKKL1's genetic distance was close to turtles, followed by amphibians and mammals, but its genetic distance was far from fishes. DKKL1 genes from different species shared distinct genomic characteristics. Meanwhile, they were also relatively conserved among themselves, at least from the perspective of classes. Notably, the transcription factors associated with spermatogenesis were also identified, containing CTCF, EWSR1, and FOXL2. DKKL1 exhibited sexually dimorphic expression only in adult gonads, which was significantly higher than that in other somatic tissues (P < 0.001), and was barely expressed in embryonic gonads. DKKL1 transcripts showed a strong signal in sperm, while faint signals were detected in other male germ cells. DKKL1 in adult testes progressively increased per month (P < 0.05), displaying a seasonal expression trait. DKKL1 was significantly downregulated in testes cells after the sex hormones (17β-estradiol and 17α-methyltestosterone) and Wnt/β-catenin inhibitor treatment (P < 0.05). Likewise, the Wnt/β-catenin inhibitor treatment dramatically repressed CTCF, EWSR1, and FOXL2 expression. Conversely, they were markedly upregulated after the 17β-estradiol and 17α-methyltestosterone treatment, suggesting that the three transcription factors might bind to different promoter regions, thereby negatively regulating DKKL1 transcription in response to the changes in the estrogen and androgen pathways, and positively controlling DKKL1 transcription in answer to the alterations in the Wnt/β-catenin pathway. Knockdown of DKKL1 significantly reduced the relative expression of HMGB2 and SPATS1 (P < 0.01), suggesting that it may be involved in seasonal spermatogenesis of P. sinensis through a positive regulatory interaction with these two genes. Overall, our findings provide novel insights into the genome evolution and potential functions of seasonal spermatogenesis of P. sinensis DKKL1.
Topics: Animals; Male; Turtles; beta Catenin; Methyltestosterone; Semen; Spermatogenesis; Estradiol; Genomics; Mammals
PubMed: 37913874
DOI: 10.1016/j.ijbiomac.2023.127696 -
Environmental Toxicology Mar 2024As a synthetic androgen, 17α-methyltestosterone (MT) is widely used in aquaculture to induce sex reversal and may pose a potential risk to aquatic organisms. This...
The effects of 17α-methyltestosterone on gonadal histology and gene expression along hypothalamic-pituitary-gonadal axis, germ cells, sex determination, and hypothalamus-pituitary-thyroid axis in zebrafish (Danio rerio).
As a synthetic androgen, 17α-methyltestosterone (MT) is widely used in aquaculture to induce sex reversal and may pose a potential risk to aquatic organisms. This ecological risk has attracted the attention of many scholars, but it is not comprehensive enough. Thus, the adverse effects of MT on zebrafish (Danio rerio) were comprehensively evaluated from gonadal histology, as well as the mRNA expression levels of 47 genes related to hypothalamic-pituitary-gonadal (HPG) axis, germ cell differentiation, sex determination, and hypothalamus-pituitary-thyroid (HPT) axis. Adult zebrafish with a female/male ratio of 5:7 were exposed to a solvent control (0.001% dimethyl sulfoxide) and three measured concentrations of MT (5, 51 and 583 ng/L) for 50 days. The results showed that MT had no significant histological effects on the ovaries of females, but the frequency of late-mature oocytes (LMO) showed a downward trend, indicating that MT could induce ovarian suppression to a certain extent. The transcriptional expression of activating transcription factor 4b1 (atf4b1), activating transcription factor 4b2 (atf4b2), calcium/calmodulin-dependent protein kinase II delta 1 (camk2d1), calcium/calmodulin-dependent protein kinase II delta 2 (camk2d2) and calcium/calmodulin-dependent protein kinase II inhibitor 2 (camk2n2) genes in the brain of females increased significantly at all treatment groups of MT, and the mRNA expression of forkhead box L2a (foxl2) and ovarian cytochrome P450 aromatase (cyp19a1a) genes in the ovaries were down-regulated by 5 and 583 ng/L group, which would translate into inhibition of oocyte development. As compared to females, MT had relatively little effects on the reproductive system of males, and only the transcriptional alterations of synaptonemal complex protein 3 (sycp3) and 17-alpha-hydroxylase/17,20-lyase (cyp17) genes were observed in the testes, not enough to affect testicular histology. In addition, MT at all treatments strongly increased corticotropin-releasing hormone (crh) transcript in the brain of females, as well as deiodinase 2 (dio2) transcript in the brain of males. The paired box protein 8 (pax8) gene was significantly decreased at 51 or 583 ng/L of MT in both female and male brains. The above results suggest that MT can pose potential adverse effects on the reproductive and thyroid endocrine system of fish.
Topics: Animals; Male; Female; Zebrafish; Methyltestosterone; Hypothalamic-Pituitary-Gonadal Axis; Thyroid Gland; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Gonads; Gene Expression; Germ Cells; RNA, Messenger; Activating Transcription Factors; Water Pollutants, Chemical
PubMed: 37994244
DOI: 10.1002/tox.24044 -
The Journal of Steroid Biochemistry and... Sep 2024Methyltestosterone (MT) is one of the most frequently misused anabolic androgenic steroids detected in doping control analysis. The metabolism of MT in humans leads to...
Methyltestosterone (MT) is one of the most frequently misused anabolic androgenic steroids detected in doping control analysis. The metabolism of MT in humans leads to several phase І metabolites and their corresponding phase Ⅱ conjugates. Previous studies have postulated the 3α-sulfoconjugate of 17α-methyl-5β-androstane-3α,17β-diol (S2) as principal sulfate metabolite of MT, with a detection window exceeding 10 days. However, a final direct and unambiguous confirmation of the structure of this metabolite is missing until now. In this study, we established an approach to detect and identify S2, using intact analysis by liquid chromatography hyphenated with tandem mass spectrometry (LC-MS/MS) without complex sample pretreatment. An in vitro study yielded the LC-MS/MS reference retention times of all 3-sulfated 17-methylandrostane-3,17-diol diastereomers, allowing for accurate structure assignment of potentially detected metabolites. In an in vivo excretion study with a single healthy male volunteer, the presence of the metabolite S2 was confirmed after a single oral dose of 10 mg MT. The reference standard was chemically synthesized, characterized by accurate mass mass spectrometry (MS) and nuclear magnetic resonance (NMR), and quantified by quantitative NMR (qNMR). Thus, this study finally provides accurate structure information on the S2 metabolite and a direct analytical method for detection of MT misuse. The availability of the reference material is expected to facilitate further evaluation and subsequent analytical method validation in anti-doping research.
Topics: Male; Humans; Methyltestosterone; Tandem Mass Spectrometry; Chromatography, Liquid; Substance Abuse Detection; Doping in Sports; Anabolic Agents; Adult; Liquid Chromatography-Mass Spectrometry
PubMed: 38710312
DOI: 10.1016/j.jsbmb.2024.106527 -
Animals : An Open Access Journal From... Jan 2024The average daily weight gain (ADG) is considered a crucial indicator for assessing growth rates in the swine industry. Therefore, investigating the gastrointestinal...
The average daily weight gain (ADG) is considered a crucial indicator for assessing growth rates in the swine industry. Therefore, investigating the gastrointestinal microbiota and serum metabolites influencing the ADG in pigs is pivotal for swine breed selection. This study involved the inclusion of 350 purebred Yorkshire pigs (age: 90 ± 2 days; body weight: 41.20 ± 4.60 kg). Concurrently, serum and fecal samples were collected during initial measurements of blood and serum indices. The pigs were categorized based on their ADG, with 27 male pigs divided into high-ADG (HADG) and low-ADG (LADG) groups based on their phenotype values. There were 12 pigs in LADG and 15 pigs in HADG. Feces and serum samples were collected on the 90th day. Microbiome and non-targeted metabolomics analyses were conducted using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Pearson correlation, with Benjamini-Hochberg (BH) adjustment, was employed to assess the associations between these variables. The abundance of and in LADG was significantly higher than in HADG, while , , , , and in LADG were significantly lower than in HADG. The concentration of glutamine, etiocholanolone glucuronide, and retinoyl beta-glucuronide in LADG was significantly higher than in HADG, while arachidonic acid, allocholic acid, oleic acid, phenylalanine, and methyltestosterone in LADG were significantly lower than in HADG. The - networks (, , methyltestosterone, phenylalanine, oleic acid, arachidonic acid, glutamine, 3-ketosphingosine, L-octanoylcarnitine, camylofin, 4-guanidinobutyrate 3-methylcyclopentadecanone) were identified as the most influential at regulating swine weight gain. These findings suggest that the gastrointestinal tract regulates the daily weight gain of pigs through the network of and . However, this study was limited to fecal and serum samples from growing and fattening boars. A comprehensive consideration of factors affecting the daily weight gain in pig production, including gender, parity, season, and breed, is warranted.
PubMed: 38254447
DOI: 10.3390/ani14020278 -
Theriogenology Feb 2024Polystyrene microplastics (PS-MPs) are important carriers of pollutants in water. 17α-Methyltestosterone (MT) is a synthetic environmental endocrine disrupting chemical...
Polystyrene microplastics (PS-MPs) are important carriers of pollutants in water. 17α-Methyltestosterone (MT) is a synthetic environmental endocrine disrupting chemical (EDC) with androgenic effects. To study the effects of PS-MPs and MT on zebrafish reproductive systems, zebrafish were exposed to 0 or 50 ng L MT, 0.5 mg∙L PS-MPs, or 50 ng∙L MT + 0.5 mg∙L PS-MPs for 21 d. The results showed that the different exposure reagents caused varying degrees of damage to the reproductive systems in zebrafish, with the extent of damage increasing as the exposure duration increased. Histological analysis of the gonads revealed that the ratio of mature oocytes and mature spermatozoa in the gonad decreased gradually with increased exposure time, with the ratio being Control > PS-MPs > MT > MT + PS-MPs in decreasing order. The results of quantitative real-time PCR (qRT‒PCR) showed that in female fish treated for 7 d, the expression of cyp11a mRNA was significantly reduced in all three treatment groups(MT, PS-MPs, and MT + PS-MPs), while in the group treated for 14 d with MT + PS-MPs, the expression of cyp19a1a and StAR mRNA was significantly increased. In male fish exposed for 21 d, the expression of cyp11a, cyp17a1, cyp19a1a, StAR, 3β-HSD, and 17β-HSD3 mRNA was significantly decreased in MT + PS-MPs. ELISA results showed that after 14 d of exposure, the levels of E2, LH, and FSH in the ovaries of female fish were significantly reduced in all three treatment groups. Similarly, the levels of T, E2, LH, and FSH in the testis of male fish were significantly reduced after 14 d of exposure to PS-MPs and MT + PS-MPs. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. The cross-generational toxicity of PS-MPs themselves may be negligible, but it can exacerbate the toxicity of MT, making the cross-generational effects more pronounced in the offspring, causing offspring mortality and malformations. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. In addition, MT caused malformations such as pericardial edema, yolk cysts, and spinal deformities in zebrafish during the incubation period.
Topics: Female; Male; Animals; Zebrafish; Methyltestosterone; Polystyrenes; Microplastics; Plastics; Gonads; RNA, Messenger; Follicle Stimulating Hormone
PubMed: 38070215
DOI: 10.1016/j.theriogenology.2023.12.004 -
Journal of Chromatography. A Jul 2024Anabolic steroids and β-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological...
Anabolic steroids and β-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (FeO@SiO-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of FeO and FeO@SiO, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 μg/L for methyltestosterone and trenbolone, and 0.02-5 μg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 μg/L. The limits of quantification were 0.02-0.40 μg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The FeO@SiO-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.
Topics: Humans; Polyethylene Glycols; Anabolic Agents; Magnetite Nanoparticles; Limit of Detection; Doping in Sports; Adsorption; Reproducibility of Results; Solid Phase Extraction; Silicon Dioxide
PubMed: 38759462
DOI: 10.1016/j.chroma.2024.464993 -
Drug Testing and Analysis Aug 2023The frequent detection of anabolic androgenic steroids (AAS) indicates their popularity among rule-breaking athletes. The so called long-term metabolites play a crucial... (Comparative Study)
Comparative Study
Detection time comparison of non-hydrolysed sulphated metabolites of metenolone, mesterolone and 17α-methyltestosterone analysed by four different mass spectrometric techniques.
The frequent detection of anabolic androgenic steroids (AAS) indicates their popularity among rule-breaking athletes. The so called long-term metabolites play a crucial role in their detection, and non-hydrolysed sulphated metabolites have gained renewed interest, as research has demonstrated their extended detection time compared to the more conventional markers (e.g., for metenolone and mesterolone). Their potential has been investigated using liquid and gas chromatography-mass spectrometry (LC- and GC-MS). However, due to their complementary nature, chances are that the most promising metabolite on one technique does not necessarily exhibit the same behaviour on the other and vice versa. Therefore, a comparison was carried out where as a trial model, metenolone, mesterolone and 17α-methyltestosterone were selected and the most likely long-term sulphated metabolites identified on four mass spectrometric instruments. Additionally, using a modified sample preparation procedure, comparison between conventional and non-hydrolysed sulphated metabolites between different GC-MS instruments was also included. When focusing on each individual marker, no cases were observed where a single metabolite provided a superior detection time on all instruments. Furthermore, for each AAS, there were incidences where a metabolite provided the best detection time on one instrument but could only be detected for a shorter period or not at all on other instruments. This demonstrates that metabolite detection windows and hence their added-value as target substance are unique and dependent on the analytical technique and not only on their pharmacokinetic behaviour. Consequently, in each case, a metabolite versus instrument evaluation is needed to maximise the probabilities of detecting doping offences.
Topics: Humans; Anabolic Agents; Anabolic Androgenic Steroids; Doping in Sports; Gas Chromatography-Mass Spectrometry; Mesterolone; Methenolone; Methyltestosterone; Substance Abuse Detection; Sulfates; Tandem Mass Spectrometry
PubMed: 37055939
DOI: 10.1002/dta.3481 -
Water Science and Technology : a... May 202417α-methyltestosterone (MT) hormone is a synthetic androgenic steroid hormone utilized to induce Nile tilapia transitioning for enhanced production yield. This study...
17α-methyltestosterone (MT) hormone is a synthetic androgenic steroid hormone utilized to induce Nile tilapia transitioning for enhanced production yield. This study specifically focuses on the removal of MT through the utilization of photocatalytic membrane reactor (PMR), which employs an in-house polyvinylidene fluoride (PVDF) ultrafiltration membrane modified with 1% nanomaterials (either TiO or α-FeO). The molecular weight cut-off (MWCO) of the in-house membrane falls within the ultrafiltration range. Under UV95W radiation, the PMR with PVDF/TiO and PVDF/α-FeO membranes achieved 100% MT removal at 140 and 160 min, respectively. The MT removal by the commercial NF03 membrane was only at 50%. In contrast, without light irradiation, the MT removal by all the membranes remained unchanged after 180 min, exhibiting lower performance. The incorporation of TiO and α-FeO enhanced water flux and MT removal of the membrane. Notably, the catalytic activity was limited by the distribution and concentration of the catalyst at the membrane surface. The water contact angle did not correlate with the water flux for the composited membrane. The degradation of MT aligned well with Pseudo-first-order kinetic models. Thus, the in-house ultrafiltration PMR demonstrated superior removal efficiency and lower operational costs than the commercial nanofiltration membrane, attributable to its photocatalytic activities.
Topics: Ultrafiltration; Membranes, Artificial; Water Pollutants, Chemical; Methyltestosterone; Catalysis; Water Purification; Titanium
PubMed: 38747961
DOI: 10.2166/wst.2024.144 -
Journal of Experimental Zoology. Part... May 2024It is well known that hormones influence and direct most facets of physiology; however, there is still contention regarding the directions of certain relationships, for...
It is well known that hormones influence and direct most facets of physiology; however, there is still contention regarding the directions of certain relationships, for example, between gonadal hormones and immunity. Among the many proposed relationships relating to gonadal-immune interactions, support for immunosuppressive effects of androgens remains prominent within physiological literature. Although ample study has been directed toward the immunosuppressive effects of androgens, considerable disagreement remains regarding their influence on immune function. In this study, we test the hypothesis that androgens inhibit immunocompetence in the American alligator (Alligator mississippiensis). Developing alligators were incubated at female-producing temperatures with a subset of individuals being exposed to 17-α-methyltestosterone (MT) before sexual determination. 17-α-methyltestosterone is a potent androgen, not aromatizable by crocodilians, that has been found to exert masculinizing effects in exposed crocodilian populations in vivo and in vitro. Additionally, a subset of animals was exposed to a novel antigen to quantify innate and acquired immune function. We recovered no significant differences in leukocyte ratios or proportions between groups and found no significant differences in innate immune function as measured by hemolysis-hemagglutination. However, we did find significant differences in acquired immune function, where masculinized individuals expressed greater antibody titers. Our findings reject the hypothesis that androgens suppress immune function; rather, androgens may be immunoenhancing to acquired humoral responses and neutral to innate humoral immunity in crocodilians.
Topics: Humans; Female; Animals; Androgens; Methyltestosterone; Steroids; Gonads; Alligators and Crocodiles; Immunosuppression Therapy
PubMed: 38374761
DOI: 10.1002/jez.2795