Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions. Our study aimed to investigate the therapeutic potential of FTY for treating HD by utilizing a well-characterized mouse model of HD (zQ175dn) and wild-type littermates. The study design included a crossover, long-term oral treatment with 1 mg/kg to 2 mg/kg FTY from the age of 15-46 weeks (n = 128). Different motor behavior and physiological parameters were assessed throughout the study. The findings revealed that FTY rescued disease-related body weight loss in a sex-dependent manner, indicating its potential to regulate metabolic disturbances and to counteract neurodegenerative processes in HD. FTY intervention also rescued testicular atrophy, restored testis tissue structure in male mice suggesting a broader impact on peripheral tissues affected by huntingtin pathology. Histological analyses of the brain revealed delayed accumulation of activated astrocytes contributing to the preservation of the neural microenvironment by reducing neuroinflammation. The extent of FTY-related disease improvement was sex-dependent. Motor functions and body weight improved mostly in female mice with sustained estrogen levels, whereas males had to compensate for the ongoing, disease-related testis atrophy and the loss of androgen production. Our study underscores the beneficial therapeutic effects of FTY on HD involving endogenous steroid hormones and their important anabolic effects. It positions FTY as a promising candidate for therapeutic interventions targeting various aspects of HD pathology. Further studies are needed to fully evaluate its therapeutic potential in patients.

• Klíčová slova
• Anabolic, Astrocytes, FTY720, Fingolimod, Huntington’s disease, Microglia, Motor function, Neurodegeneration, Neuroinflammation, S1PR1, Sphingosin-1-phosphate, Steroid hormones, ZQ175dn,
• MeSH
• fingolimod hydrochlorid * terapeutické užití   farmakologie   MeSH
• Huntingtonova nemoc * farmakoterapie   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• modulátory receptorů sfingosin-1-fosfátu * farmakologie   terapeutické užití   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• receptory sfingosin-1-fosfátu agonisté   metabolismus   MeSH
• testis účinky léků   patologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fingolimod hydrochlorid * MeSH
• modulátory receptorů sfingosin-1-fosfátu * MeSH
• receptory sfingosin-1-fosfátu MeSH

The aim of the present narrative review is to summarise the existing knowledge concerning physiological and reproductive effects of buckwheat, its mechanisms of action on various targets, as well as outlines the direction of the further studies of this functional food plant. Search for literature was performed in agreement with the PRISMA criteria in Cochrane Library, Pubmed, Web of Science, SCOPUS databases between the year 1995 and 2023. Words used to search were buckwheat, review, fertility, ovarian and mechanisms. The current review of the available literature demonstrates the high nutritional value of buckwheat, as well as high contents and number of regulatory molecules in this functional food plant. These molecules can, via multiple signalling pathways, affect a wide spectrum of physiological processes and illnesses, which suggests a therapeutic value of buckwheat substances. Furthermore, recent reports demonstrate ability of buckwheat extract to directly affect basic ovarian cell functions (proliferation, apoptosis, viability, steroidogenesis). On the other hand, understanding the character and applicability of buckwheat influence on female reproductive processes requires further studies. Keywords: Buckwheat, Nutrition, Health, Ovary, Signalling.

• MeSH
• Fagopyrum * MeSH
• fertilita fyziologie   MeSH
• lidé MeSH
• ovarium metabolismus   fyziologie   MeSH
• rostlinné extrakty terapeutické užití   farmakologie   MeSH
• rozmnožování * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• rostlinné extrakty MeSH

This is the first study on how a substance with anti-progestogenic activity affects amphibian reproduction. Mifepristone, a synthetic anti-progestin used in abortion pills, was chosen as model compound. African clawed frog (Xenopus laevis) females were exposed to four mifepristone concentrations (0.7, 9, 120, and 1380 ng∙L-1) for 30 days. A control group was also included. Egg-laying during the experiment was significantly less at the highest concentration. At the experiment's end, mifepristone-exposed and control females were randomly mated with sexually mature males. Breeding rate for females exposed to 1380 ng∙L-1 mifepristone was only 50 %. Histology revealed no significant changes in gonads, thyroid, or liver. Females exposed to 1380 ng∙L-1 mifepristone had lower estradiol levels in plasma, lower mRNA expression of lh and fsh in brain-pituitary complex, and p450scc in ovaries. In liver, mRNA level of npr was significantly increased in females exposed to 120 ng∙L-1 mifepristone. mRNA expression of mpr, erβ, dio2, and dio3 were upregulated in animals exposed to 9 ng∙L-1 and 120 ng∙L-1 mifepristone, whereas vtg expression was significantly downregulated in females exposed to 1380 ng∙L-1 mifepristone. All these findings show that exposure to compounds with anti-progestogenic activity affects the hypothalamus-pituitary-gonad axis and decreases reproductive success.

• Klíčová slova
• Amphibians, Gonads, Hormones, Mating, Progesterone receptor,
• MeSH
• estradiol MeSH
• folikuly stimulující hormon MeSH
• játra účinky léků   metabolismus   MeSH
• luteinizační hormon MeSH
• mifepriston * farmakologie   MeSH
• ovarium účinky léků   metabolismus   MeSH
• progestiny farmakologie   MeSH
• rozmnožování * účinky léků   MeSH
• Xenopus laevis * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• estradiol MeSH
• folikuly stimulující hormon MeSH
• luteinizační hormon MeSH
• mifepriston * MeSH
• progestiny MeSH

OBJECTIVE: Redox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic β-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in β-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for β-cell function and health. METHODS: We employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic β-cells. RESULTS: Glucose stimulation significantly increases ROS levels in β-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation. CONCLUSIONS: Proper functioning of pancreatic β-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic β-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in β-cell function.

• Klíčová slova
• Glucose, Pancreatic β-cells, Posttranslational modifications, ROS, Redox proteomics, Redox signaling,
• MeSH
• beta-buňky * metabolismus   účinky léků   MeSH
• fyziologická adaptace fyziologie   MeSH
• glukosa * metabolismus   MeSH
• lidé MeSH
• myši MeSH
• oxidace-redukce * MeSH
• posttranslační úpravy proteinů MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• sekrece inzulinu účinky léků   fyziologie   MeSH
• signální transdukce * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa * MeSH
• reaktivní formy kyslíku * MeSH

The somatostatin (SST) receptor family controls pituitary hormone secretion, but the distribution and specific roles of these receptors on the excitability and voltage-gated calcium signaling of hormone producing pituitary cells have not been fully characterized. Here we show that the rat pituitary gland expressed Sstr1, Sstr2, Sstr3, and Sstr5 receptor genes in a cell type-specific manner: Sstr1 and Sstr2 in thyrotrophs, Sstr3 in gonadotrophs and lactotrophs, Sstr2, Sstr3, and Sstr5 in somatotrophs, and none in corticotrophs and melanotrophs. Most gonadotrophs and thyrotrophs spontaneously fired high-amplitude single action potentials, which were silenced by SST without affecting intracellular calcium concentrations. In contrast, lactotrophs and somatotrophs spontaneously fired low-amplitude plateau-bursting action potentials in conjunction with calcium transients, both of which were silenced by SST. Moreover, SST inhibited GPCR-induced voltage-gated calcium signaling and hormone secretion in all cell types expressing SST receptors, but the inhibition was more pronounced in somatotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with both direct and indirect inhibition of voltage-gated calcium channels, the latter being driven by cell type-specific hyperpolarization. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several types of SST receptors and their slow desensitization, that SST may play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs, and that the lack of SST receptors in corticotrophs and melanotrophs keeps them excitable and ready to responses to stress.

• Klíčová slova
• Gonadotrophs, Lactotrophs, Pituitary, Somatostatin receptors, Somatotrophs, Thyrotrophs, Voltage-gated calcium influx,
• MeSH
• akční potenciály účinky léků   MeSH
• gonadotropní buňky metabolismus   účinky léků   MeSH
• hypofýza * metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• receptory somatostatinu * metabolismus   genetika   MeSH
• somatostatin metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory somatostatinu * MeSH
• somatostatin receptor 5 MeSH Prohlížeč
• somatostatin MeSH
• vápník MeSH

OBJECTIVE: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment. METHODS: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile). RESULTS: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, p < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, p < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, p = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, p = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight. CONCLUSIONS: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.

• Klíčová slova
• Thyroid dysfunction, growth restriction, low birth-weight, pre-term birth, pregnancy, screening,
• MeSH
• lidé MeSH
• porod v termínu MeSH
• prenatální diagnóza MeSH
• štítná žláza * MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• thyroxin * MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• thyroxin * MeSH

Chromosomal inversions have been identified in many natural populations and can be responsible for novel traits and rapid adaptation. In zebra finch, a large region on the Z chromosome has been subject to multiple inversions, which have pleiotropic effects on multiple traits but especially on sperm phenotypes, such as midpiece and flagellum length. To understand the effect, the Z inversion has on these traits, we examined testis and liver transcriptomes of young males at different maturation times. We compared gene expression differences among three inversion karyotypes: AA, B*B* and AB*, where B* denotes the inverted regions on Z with respect to A. In testis, 794 differentially expressed genes were found and most of them were located on chromosome Z. They were functionally enriched for sperm-related traits. We also identified clusters of co-expressed genes that matched with the inversion-related sperm phenotypes. In liver, there were some enriched functions and some overrepresentation on chromosome Z with similar location as in testis. In both tissues, the overrepresented genes were located near the distal end of Z but also in the middle of the chromosome. For the heterokaryotype, we observed several genes with one allele being dominantly expressed, similar to expression patterns in one or the other homokaryotype. This was confirmed with SNPs for three genes, and interestingly one gene, DMGDH, had allele-specific expression originating mainly from one inversion haplotype in the testis, yet both inversion haplotypes were expressed equally in the liver. This karyotype-specific difference in tissue-specific expression suggests a pleiotropic effect of the inversion and thus suggests a mechanism for divergent phenotypic effects resulting from an inversion.

• Klíčová slova
• Taeniopygia guttata, chromosome inversion, liver, testis, transcriptomics,
• MeSH
• chromozomální inverze * genetika   MeSH
• exprese genu genetika   MeSH
• fenotyp MeSH
• játra * metabolismus   MeSH
• karyotyp MeSH
• pěnkavovití * genetika   MeSH
• pohlavní chromozomy genetika   MeSH
• spermie metabolismus   MeSH
• testis * metabolismus   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The potential of microRNAs to protect the female reproductive system from the toxic influence of oil-related environmental contaminants has not yet been examined. The aim of the present study was to examine the ability of the microRNA miR-152 to prevent the toxic effects of toluene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without toluene (0, 10 and 100 ng/ml). The expression of miR-152; cell viability; proliferation (accumulation of PCNA, cyclin B1 and BrdU); cytoplasmic/mitochondrial apoptosis (accumulation of bax and caspase 3); and release of progesterone, testosterone and estradiol were quantified via RT-qPCR, the Trypan blue exclusion test, quantitative immunocytochemistry, the BrdU assay and ELISA. The addition of toluene reduced cell viability, decreased the levels of all the measured markers of proliferation and the release of all the measured steroid hormones, and promoted the expression of apoptosis markers. Transfection of cells with miR-152 mimics increased the expression of miR-152, cell proliferation, and progesterone release but reduced apoptosis and the release of testosterone and estradiol. Moreover, miR-152 prevented or inhibited all the toluene effects in addition to its inhibitory effect on testosterone and estradiol release. The present results demonstrate that miR-152 can protect ovarian cells from the harmful influence of toluene.

• MeSH
• apoptóza * účinky léků   MeSH
• estradiol MeSH
• folikulární buňky * účinky léků   metabolismus   MeSH
• kultivované buňky MeSH
• mikro RNA * metabolismus   genetika   MeSH
• prasata MeSH
• progesteron metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• toluen * toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• estradiol MeSH
• mikro RNA * MeSH
• progesteron MeSH
• toluen * MeSH

Most eukaryotes maintain the stability of their cellular genome sizes to ensure genome transmission to offspring through sexual reproduction. However, some alter their genome size by selectively eliminating parts or increasing ploidy at specific developmental stages. This phenomenon of genome elimination or whole genome duplication occurs in animal hybrids reproducing asexually. Such genome alterations occur during gonocyte development ensuring successful reproduction of these hybrids. Although multiple examples of genome alterations are known, the underlying molecular and cellular processes involved in selective genome elimination and duplication remain largely unknown. Here, we uncovered the process of selective genome elimination and genome endoreplication in hemiclonal fish hybrids from the genus Hypseleotris. Specifically, we examined parental sexual species H. bucephala and hybrid H. bucephala × H. gymnocephala (HB × HX). We observed micronuclei in the cytoplasm of gonial cells in the gonads of hybrids, but not in the parental sexual species. We also observed misaligned chromosomes during mitosis which were unable to attach to the spindle. Moreover, we found that misaligned chromosomes lag during anaphase and subsequently enclose in the micronuclei. Using whole mount immunofluorescent staining, we showed that chromatid segregation has failed in lagging chromosomes. We also performed three-dimensional comparative genomic hybridization (3D-CGH) using species-specific probes to determine the role of micronuclei in selective genome elimination. We repeatedly observed that misaligned chromosomes of the H. bucephala genome were preferentially enclosed in micronuclei of hybrids. In addition, we detected mitotic cells without a mitotic spindle as a potential cause of genome duplication. We conclude that selective genome elimination in the gonads of hybrids occurs through gradual elimination of individual chromosomes of one parental genome. Such chromosomes, unable to attach to the spindle, lag and become enclosed in micronuclei.

• Klíčová slova
• Asexual, Carp gudgeon, Gonocytes, Histone modification, Hybridogenesis, Micronucleus,
• MeSH
• chromozomy genetika   MeSH
• délka genomu MeSH
• genom * MeSH
• gonády metabolismus   MeSH
• hybridizace genetická MeSH
• mitóza genetika   MeSH
• ryby genetika   MeSH
• segregace chromozomů genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

• Klíčová slova
• 17α-Ethynylestradiol, DNA methylation, EE2, Endocrine disruptors, Histone-to-protamine exchange, Post-translational modifications, Sperm, Testis, Transgenerational study,
• MeSH
• endokrinní disruptory farmakologie   toxicita   MeSH
• epigeneze genetická * účinky léků   MeSH
• ethinylestradiol * farmakologie   MeSH
• histony * metabolismus   MeSH
• myši MeSH
• posttranslační úpravy proteinů účinky léků   MeSH
• protaminy * metabolismus   genetika   MeSH
• spermatogeneze * účinky léků   genetika   MeSH
• spermie účinky léků   metabolismus   MeSH
• testis * účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokrinní disruptory MeSH
• ethinylestradiol * MeSH
• histony * MeSH
• protaminy * MeSH