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Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterus albus.Biology of Sex Differences Oct 2023Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism...
BACKGROUND
Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.
METHODS
We produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.
RESULTS
This effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.
CONCLUSIONS
This study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M. albus, which will also enrich the sex differentiation mechanism of teleosts.
Topics: Male; Animals; Female; RNA, Long Noncoding; Gonads; Ovary; Testis; Sex Differentiation; Smegmamorpha
PubMed: 37880697
DOI: 10.1186/s13293-023-00559-y -
BMC Genomics Jul 2017Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal...
BACKGROUND
Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens and aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing to characterise zebrafish gonadal transcriptomes and investigate the effects of 17α-methyltestosterone on gonadal differentiation.
RESULTS
At a morphological level, 17α-methyltestosterone (MT) masculinised gonads and accelerated spermatogenesis, and these changes were paralleled in masculinisation and de-feminisation of gonadal transcriptomes. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt1, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It also repressed expression of ovarian development and folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT treatment altered epigenetic modification of histones in zebrafish gonads. Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in control ovaries compared to MT-treated testes and control testes were not statistically significant during early gonad development (40 dpf).
CONCLUSION
Our study suggests that both androgen production and aromatase inhibition are important for androgen-induced gonadal masculinisation and natural testicular differentiation in zebrafish.
Topics: Animals; Female; Male; Methyltestosterone; Ovary; Sex Characteristics; Sex Ratio; Spermatogenesis; Testis; Transcriptome; Zebrafish
PubMed: 28738802
DOI: 10.1186/s12864-017-3915-z -
Heliyon Dec 2022The 17α-methyltestosterone is the most common synthetic hormone used in male mono-sex production of Nile tilapia, . The current research aimed at finding out the most...
The 17α-methyltestosterone is the most common synthetic hormone used in male mono-sex production of Nile tilapia, . The current research aimed at finding out the most effective dose of 17α-methyltestosterone to produce quality Nile tilapia fry. Soon after absorbing the yolk sac, Nile tilapia fry was fed with a mixture of commercial fish feed and 17α-methyltestosterone for 28 days. Five doses of 17α-methyltestosterone, i.e., 0 mg, 50 mg, 60 mg, 70 mg, and 80 mg per kg feed, were used to treat tilapia that has been reared for additional 90 days to compare sex reversal, development, and survival rates. Both gonad histology and Squash test were performed to expose the sex percentage of accurately. The highest male 94.44% was obtained at 60 mg 17α-MT/kg feed dose followed by 91.67%, 88.89%, 86.11%, and 47.22% at 70, 80, 50, and 0 mg 17α-MT/kg feed dose. The groups treated with 17α-methyltestosterone hormone showed superior growth performance in comparison to the control group. The highest weight (14.62 ± 0.59 g) and length (92.18 ± 3.01 mm) were found at 60 mg dose whereas the lowest weight (8.64 ± 0.38 g) and length (70.17 ± 3.75 mm) were in the control group. The group given 60 mg 17α-MT feed represented the highest survival rate (84.10%) among other hormone-treated groups. The study disclosed that 60 mg 17α-MT/kg feed might be treated as the optimal dose for producing quality mono-sex male tilapia in the commercial hatchery.
PubMed: 36536906
DOI: 10.1016/j.heliyon.2022.e12252 -
Molecules (Basel, Switzerland) Jan 2023Steroid hormone molecules may exhibit very different functionalities based on the associated functional groups and their 3D arrangements in space, i.e., absolute...
Steroid hormone molecules may exhibit very different functionalities based on the associated functional groups and their 3D arrangements in space, i.e., absolute configurations and conformations. Infrared (IR) and vibrational circular dichroism (VCD) spectra of four different steroid hormones, namely dehydroepiandrosterone (DHEA), 17-methyltestosterone (MTTT), (16α,17)-epoxyprogesterone (Epoxy-P4), and dehydroepiandrosterone acetate (AcO-DHEA), were measured in deuterated dimethyl sulfoxide and some also in carbon tetrachloride. Extensive conformational searches were carried out using the recent developed conformer-rotamer ensemble sampling tool (CREST) which also accounts for solvent effects using an implicit solvation model. All the CREST conformational candidates were then reoptimized at the B3LYP-D3BJ/def2-TZVPD with the PCM of solvent. The good agreements between the experimental IR and VCD spectra and the theoretical simulations provide a conclusive information about their conformational distribution and absolute configurations. The experimental and theoretical IR and VCD spectra of AcO-DHEA in the carbonyl and alkene stretching region showed some discrepancies, and the possible causes related to solvent effects, large amplitude motions and levels of theory used in the modelling were explored in detail. As part of the investigation, additional calculations at the B3LYP-D3BJ/6-31++G (2d,p) and B3LYP-D3BJ/cc-pVTZ levels, as well as some 'mixed' calculations with the double-hybrid functional B2PLYP-D3 were also carried out. The results indicate that the double-hybrid functional is important for predicting the correct IR band pattern in the carbonyl and alkene stretching region.
PubMed: 36677830
DOI: 10.3390/molecules28020771 -
International Journal of Molecular... Feb 202317α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ...
17α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ cell maturation in . To further investigate the regulation of gonadal development by MT through the hypothalamic-pituitary-gonadal (HPG) axis, were exposed to 0, 25, 50, and 100 ng/L of MT for 7, 14, and 21 days. We analyzed its biological indicators, gonadotropin-releasing hormone (GnRH), gonadotropins, reproduction-related gene expression, and brain tissue transcriptome profiles. We found a significant decrease in the gonadosomatic index (GSI) in males exposed to MT for 21 days compared to the control group. GnRH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, as well as the expressions of the , , , , and genes, were significantly reduced in the brains of both male and female fish when exposed to 100 ng/L MT for 14 days compared to the controls. Therefore, we further constructed four RNA-seq libraries from 100 ng/L MT-treated groups of male and female fish, obtaining 2412 and 2509 DEGs in male and female brain tissue, respectively. Three common pathways were observed to be affected in both sexes after exposure to MT, namely, nicotinate and nicotinamide metabolism, focal adhesion, and cell adhesion molecules. Furthermore, we found that MT affected the PI3K/Akt/FoxO3a signaling pathway through the upregulation of and , and the downregulation of and . Therefore, we hypothesize that MT interferes with the levels of gonadotropin-releasing hormone (GnRH, FSH, and LH) in brains through the PI3K/Akt/FoxO3a signaling pathway, and affects the expression of key genes in the hormone production pathway (, and ) to interfere with the stability of the HPG axis, thus leading to abnormal gonadal development. This study provides a multidimensional perspective on the damaging effects of MT on fish and confirms that is a suitable model animal for aquatic toxicology.
Topics: Animals; Female; Male; Methyltestosterone; Transcriptome; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Cyprinidae; Gonadal Steroid Hormones; Cypriniformes; Brain; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone
PubMed: 36834982
DOI: 10.3390/ijms24043571 -
Zebrafish Dec 2022Severely skewed sex ratios in zebrafish stocks can pose significant hurdles for line propagation and sperm cryopreservation. To overcome female-biased sex ratios in... (Review)
Review
Severely skewed sex ratios in zebrafish stocks can pose significant hurdles for line propagation and sperm cryopreservation. To overcome female-biased sex ratios in stocks derived from imported sperm samples, the Zebrafish International Resource Center has implemented routine supplementation of larval food with 17α-methyltestosterone to skew gonadal sex differentiation toward masculinization. Resulting stocks averaged 80% males.
Topics: Male; Female; Animals; Zebrafish; Methyltestosterone; Semen; Gonads; Sex Differentiation
PubMed: 36318811
DOI: 10.1089/zeb.2022.0029 -
Genes May 2024It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females...
It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales of for subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth of , while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes ( and ) while up-regulating male-related genes () in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role in sex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT in and offers an initial insight into the underlying mechanism of sexual reversal in this species.
Topics: Animals; Methyltestosterone; Male; Female; Sex Differentiation; Perciformes; Testis; Fishes; Fish Proteins
PubMed: 38790234
DOI: 10.3390/genes15050605 -
Clinical Journal of the American... Apr 2019Many aspects of CKD management rely heavily on patient self-care, including medication and dietary adherence, self-monitoring of BP, and daily physical activity. Growing...
BACKGROUND AND OBJECTIVES
Many aspects of CKD management rely heavily on patient self-care, including medication and dietary adherence, self-monitoring of BP, and daily physical activity. Growing evidence suggests that incorporating smartphone-based applications can support self-care in CKD and chronic disease more generally.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We identified applications targeting patients with CKD by conducting a search of the US Apple App Store (iOS) and Google Play Store (Android) using the following four phrases: "kidney disease," "renal," "dialysis," and "kidney transplant." We considered the first 50 applications for each search term on each application store. We adapted a previously described framework for assessment of mobile health applications to account for kidney disease-specific content areas and evaluated applications on their types of patient engagement, quality, usability, and safety. Engagement and quality were assessed by both a patient and a nephrologist, usability was assessed by a patient, and safety was assessed by a nephrologist. Overall, two patients with CKD and three nephrologists performed the evaluations. We examined pairwise correlations between patient, nephrologist, and consumer ratings of application quality.
RESULTS
Our search strategy identified 174 unique applications on Android and 165 unique applications on iOS. After excluding applications that were not related to kidney disease, were not patient facing, or were last updated before 2014, 12 Android-only applications, 11 iOS-only applications, and five dual-platform applications remained. Patient and nephrologist application quality ratings, assessed by the net promoter score, were not correlated (=0.36; =0.06). Consumer ratings on the application stores did not correlate with patient ratings of application quality (=0.34; =0.18).
CONCLUSIONS
Only a small subset of CKD applications was highly rated by both patients and nephrologists. Patients' impressions of application quality are not directly linked to consumer application ratings or nephrologist impressions.
Topics: Attitude of Health Personnel; Humans; Mobile Applications; Nephrology; Patient Participation; Renal Insufficiency, Chronic; Self Care; Smartphone
PubMed: 30898873
DOI: 10.2215/CJN.10370818