Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development, partially mediated by extracellular vesicles (EVs) encapsulated with microRNAs (miRNAs) and present in the follicular fluid (FF). Here, we aimed to decipher the dynamics of the miRNAs in EVs from equine FF aspirated in vivo during different stages of follicular development, namely, predeviation (PreDev; 18-20 mm), deviation (Dev; 22-25 mm), postdeviation (PostDev; 26-29 mm), preovulatory (PreOV; 30-35 mm), and impending ovulation (IMP; ∼40 mm). Approximately 176 known miRNAs were found in all groups with 144 mutually detected among all groups. Cluster analysis exhibited 15 different expression patterns during follicular development. Among these patterns, a group of 22 miRNAs (including miR-146b-5p, miR-140, and miR-143) exhibited a sharp reduction in expression from the PreDev until the PreOV stage. Another cluster of 23 miRNAs (including miR-106b, miR-199a-5p, and miR-125a-5p) exhibited a stable expression pattern at the PreDev stage until the PostDev stage, with a significant increase at the PreOV stage followed by a significant decrease at the IMP stage. In conclusion, this study provides greater insights into the stage-specific expression dynamics of FF EV-miRNAs during equine follicular development, which may propose novel approaches to improve ART and provide new biomarkers to facilitate the assessment of ovarian pathophysiological conditions.
- MeSH
- extracelulární vezikuly * genetika metabolismus MeSH
- folikulární tekutina metabolismus MeSH
- koně MeSH
- lidé MeSH
- mikro RNA * metabolismus MeSH
- ovariální folikul metabolismus MeSH
- ovulace genetika MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- anovulace MeSH
- děložní krvácení * diagnóza etiologie komplikace terapie MeSH
- gynekologická onemocnění diagnóza epidemiologie terapie MeSH
- lidé MeSH
- menstruační cyklus fyziologie MeSH
- menstruační poruchy diagnóza etiologie patofyziologie terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.
- MeSH
- analýza spermatu MeSH
- fertilizace in vitro metody MeSH
- infertilita * diagnóza etiologie patofyziologie terapie MeSH
- klinické laboratorní techniky MeSH
- lidé MeSH
- oocyty fyziologie růst a vývoj MeSH
- superovulace MeSH
- umělá inseminace metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Endocrinal interactions are one of the most crucial regulatory mechanisms that maintain the state of homeostasis in humans. Processes such as oogenesis, folliculogenesis, menstruation and pregnancy remain under hormonal control. A key role in folliculogenesis is played by granulosa cells. Moreover, granulosa cells take part in corpus luteum formation after ovulation. Because of that, it is important to understand the ways in which the granulosa cells, associated with those processes, respond to hormonal stimulus. In the present study, a transcriptomic analysis of human granulosa cells (GCs) was carried out with the use of expression microarrays. The results were validated by RT-qPCR. The total RNA was isolated after 1st, 7th, 15th and 30th days of long-term primary cultures. The main focus of this work was placed on the genes belonging to "Response to estradiol", "Response to follicle-stimulating-hormone", "Cellular response to hormone stimulus", "Cellular hormone metabolic process" and "Hormone biosynthetic process" gene ontology groups. These groups of genes have been associated with GC hormone metabolism and cellular response to hormones. Eighty genes belonging to these groups were identified. Those that were members of more than one of the analyzed gene ontology groups, or exhibited unique expression patterns, were selected for further analysis. All of the selected genes were described, with their expression patterns detailed. In this manuscript, two gene expression patterns have been described. The first one showed large downregulation of genes in the later stages of culture, with the second one presenting upregulation of expression after day 1 of IVC. The present research was focused on six genes found to be the most important for steroidogenesis: STAR, POR, CYP11A1, ADM, GCLC, IL1B, as well as three genes of higher expression at the later stages of long-term in vitro culture: NR2F2, BMP4, COL1A1. The main goal of the presented study was to select genes involved in response to hormonal stimulus and hormone metabolism in GC long-term in vitro culture.
- MeSH
- estradiol genetika MeSH
- folikulární buňky metabolismus MeSH
- folikuly stimulující hormon genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- oogeneze MeSH
- ovariální folikul růst a vývoj MeSH
- ovulace MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Clostilbegyt, Femara, Dracenax, Lerana,
- MeSH
- anovulace * etiologie farmakoterapie MeSH
- gonadotropiny aplikace a dávkování ekonomika farmakologie MeSH
- indukce ovulace ekonomika metody MeSH
- inhibitory aromatasy aplikace a dávkování farmakokinetika farmakologie MeSH
- klomifen aplikace a dávkování farmakologie MeSH
- letrozol aplikace a dávkování farmakokinetika farmakologie MeSH
- lidé MeSH
- náklady na léky MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- ženská infertilita etiologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Granulosa cells (GCs) have many functions in the endocrine system. Most notably, they produce progesterone following ovulation. However, it has recently been proven that GCs can change their properties when subjected to long‑term culture. In the present study, GCs were collected from hyper‑stimulated ovarian follicles during in vitro fertilization procedures. They were grown in vitro, in a long‑term manner. RNA was collected following 1, 7, 15 and 30 days of culture. Expression microarrays were used for analysis, which allowed to identify groups of genes characteristic for particular cellular processes. In addition, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to validate the obtained results. Two ontological groups characteristic for processes associated with the development and morphogenesis of the heart were identified during the analyses: 'Heart development' and 'heart morphogenesis'. The results of the microarrays revealed that the highest change in expression was demonstrated by the lysyl Oxidase, oxytocin receptor, nexilin F‑actin binding protein, and cysteine‑rich protein 3 genes. The lowest change was exhibited by odd‑skipped related transcription factor 1, plakophilin 2, transcription growth factor‑β receptor 1, and kinesin family member 3A. The direction of changes was confirmed by RT‑qPCR results. In the present study, it was suggested that GCs may have the potential to differentiate towards other cell types under long‑term in vitro culture conditions. Thus, genes belonging to the presented ontological groups can be considered as novel markers of proliferation and differentiation of GCs towards the heart muscle cells.
- MeSH
- buněčná diferenciace genetika MeSH
- buněčné kultury * MeSH
- buněčný rodokmen genetika MeSH
- folikulární buňky cytologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- lysyloxidasa genetika MeSH
- morfogeneze genetika MeSH
- ovariální folikul cytologie metabolismus MeSH
- ovulace genetika MeSH
- progesteron genetika MeSH
- receptory oxytocinu genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Management pacientek s nízkou odpovědí na kontrolovanou ovariální hyperstimulaci (KOH) je obtížnou a pořád kontroverzní otázkou. Přestože během posledních několika dekád došlo k výrazným pokrokům v reprodukční medicíně, dosud chybí konsenzus týkající se léčby neplodnosti v této populační skupině. Nově objevující se důkazy jasně hovoří o tom, že pro navýšení úspěšnosti léčení sterility je z hlediska kumulativní úspěšnosti IVF cyklu důležitý počet získaných oocytů, který se dá optimalizovat správným odhadem ovariální rezervy s přihlédnutím k věku pacientky. Léta existující paradigma folikulogeneze (jeden cyklus = jedná kohorta folikulů odpovídajících na stimulaci) byla překonána teorií folikulárních vln, což otevřelo nové terapeutické možnosti u starších pacientek s malou ovariální rezervou. V tomto souhrnném článku jsou uvedené aktuální informace týkající se problematiky pacientek s nízkou reakcí na KOH, včetně přesnější klasifikace těchto pacientek dle expertní skupiny POSEIDON a současné poznatky o Duostim protokolu – slibným nástrojem pro zlepšení výsledků terapie sterility u žen s nedostatečnou odezvou ovarií na KOH.
Management of patients with poor ovarian response to controlled ovarian hyperstimulation (COH) is a challenging and still a controversial issue. Despite the advances in reproductive medicine in the past decades, there is still no consensus regarding fertility treatment of this population group. In terms of improving the clinical outcomes by increasing the cumulative live birth rates per each started IVF cycle, increasing evidence demonstrate the importance of the number of oocytes retrieved after COH, which can be optimized by correct evaluation of the ovarian reserve, also taking into consideration the woman’s age. The classic paradigm of folliculogenesis (one cycle = one cohort of follicles responsive to stimulation) has been overtaken by the theory of follicular waves, which opened new therapeutical possibilities for the advanced maternal age patients with low ovarian reserve. This article is a review of the up-to-date information regarding low responsive patients, including more precise classification of these patients by the POSEIDON expert group, and a review of the existing data about the Duostim protocol – a promising instrument for improving the results of the fertility treatment in poor responders.
- Klíčová slova
- DUOSTIM protokol,
- MeSH
- anovulace terapie MeSH
- fertilizace in vitro metody MeSH
- indukce ovulace * MeSH
- lidé MeSH
- management nemoci MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- MeSH
- asistovaná reprodukce * MeSH
- časové faktory MeSH
- choriogonadotropin aplikace a dávkování MeSH
- diagnostické techniky porodnicko-gynekologické MeSH
- endosonografie metody MeSH
- hormon uvolňující gonadotropiny agonisté aplikace a dávkování MeSH
- indukce ovulace metody MeSH
- lidé MeSH
- luteinizační hormon účinky léků MeSH
- oocyty růst a vývoj účinky léků MeSH
- ovulace účinky léků MeSH
- vagina MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
