Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age, characterized by a spectrum of reproductive, endocrine, and metabolic disturbances. The etiology of PCOS encompasses a complex interplay of genetic, metabolic, inflammatory, and oxidative factors, though the precise pathological mechanisms remain inadequately understood. Despite considerable variability in the clinical characteristics and biochemical profiles among individuals with PCOS, abnormalities in follicular development are a hallmark of the condition. Granulosa cells, integral to follicular development, play a pivotal role in follicle maturation. Recent studies have established a strong correlation between granulosa cell programmed cell death and follicular atresia in PCOS. This review provides a comprehensive analysis of the current understanding of granulosa cell programmed cell death and its contribution to follicular atresia within the pathophysiology of PCOS, providing a foundation for future research endeavors. Key words Follicular atresia, Hyperandrogenism, Insulin resistance, Polycystic ovary syndrome, Programmed cell death of granulosa cells.

• MeSH
• apoptóza * MeSH
• folikulární atrézie * metabolismus   MeSH
• folikulární buňky * metabolismus   patologie   MeSH
• lidé MeSH
• ovariální folikul metabolismus   patologie   MeSH
• syndrom polycystických ovarií * patologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

• MeSH
• adiponektin metabolismus   krev   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus   MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• folikuly stimulující hormon krev   MeSH
• GABA metabolismus   MeSH
• hormon uvolňující gonadotropiny metabolismus   MeSH
• hypothalamus * metabolismus   účinky léků   patologie   MeSH
• inzulinová rezistence MeSH
• krysa rodu rattus MeSH
• leptin krev   metabolismus   MeSH
• letrozol farmakologie   MeSH
• luteinizační hormon krev   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar * MeSH
• pyroptóza * účinky léků   MeSH
• syndrom polycystických ovarií * chemicky indukované   metabolismus   farmakoterapie   patologie   MeSH
• testosteron krev   MeSH
• triglyceridy krev   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• lidé MeSH
• syndrom polycystických ovarií * etiologie   patofyziologie   patologie   terapie   MeSH
• ženská infertilita etiologie   terapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• novinové články MeSH

Polycystic ovary syndrome (PCOS) is associated with multiple risk factors for cardiovascular diseases, including insulin resistance, diabetes mellitus type 2, obesity, hypertension, and dyslipidaemia. Many studies have assessed the role of adipokines in the etiopathogenesis of PCOS, however, no single biomarker has been recognized to be in causal relation to the syndrome. Apelin has been identified as a new adipokine linked to obesity and insulin resistance. Some studies demonstrated that the apelin / apelin receptor could play a pivotal role in the pathogenesis of polycystic ovary syndrome, however the other yielded controversial results. Underlying mechanisms of possible involvement of apelin/apelin receptor complex are discussed.

• MeSH
• adipokiny MeSH
• apelin MeSH
• biologické markery MeSH
• inzulinová rezistence * MeSH
• lidé MeSH
• syndrom polycystických ovarií * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Kůra nadledvin je zdrojem významného množství steroidních hormonů a jejich metabolitů s androgenním účinkem různého stupně. Donedávna byl považován příspěvek těchto látek k celkovému androgennímu potenciálu člověka za nepříliš významný, ale současné studie ukazují, že některé C19 steroidy adrenálního původu mají evidentně vysoký androgenní účinek. Jde především o 11-oxo- a 11β-hydroxyderiváty testosteronu a dihydrotestosteronu, jejichž androgenizující efekt předčí významně aktivitu testosteronu nebo dihydrotestosteronu. Protože stanovení 11-oxygenovaných C19-steroidů nebylo až na výjimky dosud v laboratořích zavedeno, byl náš dosavadní pohled na hormonální pozadí některých hyperandrogenních stavů zkreslen. Tato skutečnost má klinický význam např. u různých typů vrozené adrenální hyperplazie s androgenizací nebo u syndromu polycystických ovarií. Zde by laboratorní měření uvedených látek mohlo pomoci lépe zhodnotit celkový androgenní stav u pacientů s těmito onemocněními. Mění se i současný pohled na léčbu karcinomu prostaty androgenní deprivací, která vřazuje jenom účinek testikulárních androgenů. K dokonalejší blokádě androgenů by měla pomoci vedle současně prováděné deprivační terapie i souběžná blokáda sekrece adrenálních C19-steroidů, ať již účinnými kortikoidy, nebo adrenostatiky.

The adrenal cortex is an important source of a series of steroid hormones and their metabolites exerting an androgenic activity of some degree. Until recently their androgenic potency was considered to be low, but some new discoveries have shown that some of the C19-steroids of adrenal origin evidently possess very high androgenic activity. Especially 11-oxygenated derivatives of testosterone and dihydrotestosterone exert androgen potency higher than non-oxygenated analogues. Whereas the measurements of the levels of 11-oxygenated androgens until now has not been introduced in routine laboratories of clinical biochemistry, our view on some hyperandrogenic statusesis incomplete. This matter of fact has a clinical significance in our conception of hyperandrogenic types of congenital adrenal hyperplasia or polycystic ovary syndrome. In these situations the analysis of 11-oxygeneted adrenal androgens could help better to evaluate the androgenic status of the patients. Another point of attention is the present form of the treatment of prostate carcinoma by androgen deprivation method, which is blocking only the androgens of testicular origin. A more completed blocking of androgens in the prostate should be the present androgen deprivation therapy and concomitant block of the adrenal C19-steroids either by highly efficient corticosteroids or by adrenostatics.

• Klíčová slova
• 11-ketotestosteron, androgen-deprivační terapie,
• MeSH
• androgeny * analýza   chemie   krev   MeSH
• hormony kůry nadledvin * analýza   fyziologie   klasifikace   krev   metabolismus   MeSH
• kongenitální adrenální hyperplazie krev   MeSH
• lidé MeSH
• syndrom polycystických ovarií patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7beta-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fatty-liver index, triglycerides, cytokines (IL-2, IL-13, IFN-gamma). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms.

• MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• endokrinní disruptory krev   MeSH
• estrogeny krev   MeSH
• index tělesné hmotnosti MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• obezita krev   epidemiologie   patologie   MeSH
• studie případů a kontrol MeSH
• syndrom polycystických ovarií krev   epidemiologie   patologie   MeSH
• testosteron krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Vitamin D3 is well-known as a major regulator of calcium and phosphorus homeostasis. A growing body of evidence highlights its crucial role in the regulation of reproductive processes in females. The role of vitamin D3 in the female reproductive tract has been extensively investigated because its receptor is abundant in reproductive organs, including ovary. Importantly, besides expression of vitamin D3 receptor, the ovary is an extrarenal site of vitamin D3 metabolism. The influence of vitamin D3 on follicular development and ovarian steroidogenesis has been investigated. Furthermore, vitamin D3 deficiency has also been associated with polycystic ovary syndrome, premature ovarian failure and ovarian cancer. The objective of this review is to summarize our knowledge about the contribution of vitamin D3 to physiological and pathological processes within the ovary.

• MeSH
• cholekalciferol metabolismus   MeSH
• lidé MeSH
• nedostatek vitaminu D metabolismus   MeSH
• ovarium metabolismus   patologie   MeSH
• receptory kalcitriolu metabolismus   MeSH
• syndrom polycystických ovarií metabolismus   patologie   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Ovarian follicle steroidogenesis associated with embryo quality results in a successful pregnancy. Each follicle consists of an oocyte surrounded by granulosa cells, which secrete several steroid and peptide hormones. Follicles harvested from women who conceived after assisted reproductive therapy (ART) had significantly higher estradiol levels in follicular fluids than the follicles from women who failed to conceive after ART. The higher follicular estradiol levels correlate well with successful fertilization following ART. Mitochondria are the central sites for steroid hormone biosynthesis. The first and rate-limiting step in the biosynthesis of steroid hormones occurs in the mitochondria of granulosa cells. In the present study, we hypothesized that the mitochondria in granulosa cells are critical for maintaining oocyte quality and fertility capacity. This study aims to clarify the relationship between mitochondrial function and granulosa cell steroidogenesis, and the relationship between hormone levels and fertility capacity. Sera, follicular fluids and granulosa cells were obtained from individuals undergoing IVF-ET treatment. The oocyte numbers, oocyte quality, fertilization rate, and pregnancy rate were also recorded. The patients who provided the granulosa cells were further classified into four groups: endometriosis, ovarian endometrioma, endometriosis without ovarian endometrioma, and polycystic ovary syndrome (PCOS); patients with other female factor infertility and male factor infertility were used as controls. We measured the levels of estradiol (E2) by radioimmunoassay. Concurrently, we analyzed the mitochondrial mass and membrane potential, and apoptosis by flow cytometry using nonyl acridine orange, TMRE, Annexin V-FITC and PI. Mitochondrial morphology was visualized by transfection with pLV-mitoDsRed. In addition, we assessed the protein levels of steroidogenic enzymes, steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) by Western blot. The results showed significantly decreased serum E2 and follicular E2 levels, and decreased IVF outcomes, in the patients with endometriosis. Reduced mitochondrial mass and decreased mitochondrial membrane potential were correlated with lower E2. Furthermore, a significant decrease in StAR and 3β-HSD was found in patients with ovarian endometrioma. The enzyme levels of StAR and 3β-HSD were highly correlated with E2 levels. Finally, elevated cumulus cell apoptosis was found in the patient group with ovarian endometrioma and PCOS. In conclusion, mitochondrial dysfunction of human granulosa cells may contribute to the decline of steroidogenesis, decreased fertilization rate, oocyte maturation rate, and oocyte quality, and it can ultimately jeopardize fertility.

• MeSH
• apoptóza MeSH
• biologické modely MeSH
• cysty patologie   MeSH
• dospělí MeSH
• endometrióza krev   komplikace   patologie   MeSH
• estradiol krev   MeSH
• fertilita * MeSH
• fertilizace in vitro MeSH
• folikulární buňky metabolismus   MeSH
• folikulární tekutina metabolismus   MeSH
• kumulární buňky metabolismus   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• oocyty metabolismus   MeSH
• progesteron krev   MeSH
• steroidy biosyntéza   MeSH
• syndrom polycystických ovarií krev   komplikace   patologie   MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• ženská infertilita krev   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dysmenorea diagnóza   patofyziologie   MeSH
• lidé MeSH
• menstruační poruchy diagnóza   klasifikace   patofyziologie   MeSH
• nemoci ovaria * diagnóza   klasifikace   patofyziologie   MeSH
• ovarium fyziologie   MeSH
• premenstruační syndrom diagnóza   MeSH
• syndrom polycystických ovarií farmakoterapie   patologie   MeSH
• testy funkce vaječníku MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

• MeSH
• alergologie a imunologie MeSH
• antifosfolipidový syndrom patologie   MeSH
• endometrióza diagnóza   imunologie   patologie   MeSH
• komorbidita MeSH
• lidé MeSH
• mužská infertilita imunologie   MeSH
• preeklampsie imunologie   patofyziologie   MeSH
• reprodukční lékařství MeSH
• syndrom polycystických ovarií diagnóza   patologie   MeSH
• ženská infertilita imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• souhrny MeSH