Historicky spíše ignorovaná mužská neplodnost zapříčiňuje samostatně nebo v kombinaci neplodnost páru přibližně v 60 % případů. Nemožnost páru zplodit potomka vede k psychosociálnímu stresu. Úlohou systematické diagnostiky a terapie neplodnosti muže je rozpoznání příčiny, snaha o zlepšení tvorby spermií a zvýšení šance na úspěšné početí.
Historically rather ignored male infertility is alone or in combination the cause of approximately 60% infertile couples. Inability of couple to conceive leads to psychosocial stress. Role of systematic diagnostics and treatment of male infertility is to understand the cause, improve spermatogenesis and increase chances of successful fertilization.
- MeSH
- analýza spermatu metody MeSH
- antioxidancia terapeutické užití MeSH
- choriogonadotropin aplikace a dávkování terapeutické užití MeSH
- diagnostické techniky endokrinologické MeSH
- genetické testování MeSH
- inhibitory aromatasy terapeutické užití MeSH
- mužská infertilita * diagnóza etiologie farmakoterapie MeSH
- selektivní modulátory estrogenních receptorů aplikace a dávkování terapeutické užití MeSH
- Check Tag
- mužské pohlaví MeSH
- MeSH
- biologické markery MeSH
- lidé MeSH
- novorozenec MeSH
- placentární růstový faktor MeSH
- předčasná porodní činnost * MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental syncytiotrophoblast formation. To mediate cell-to-cell fusion, Syncytin-1 requires specific interaction with its cognate receptor. Two trimeric transmembrane proteins, Alanine, Serine, Cysteine Transporters 1 and 2 (ASCT1 and ASCT2), were suggested and widely accepted as Syncytin-1 cellular receptors. To quantitatively assess the individual contributions of human ASCT1 and ASCT2 to the fusogenic activity of Syncytin-1, we developed a model system where the ASCT1 and ASCT2 double knockout was rescued by ectopic expression of either ASCT1 or ASCT2. We demonstrated that ASCT2 was required for Syncytin-1 binding, cellular entry, and cell-to-cell fusion, while ASCT1 was not involved in this receptor interaction. We experimentally validated the ASCT1-ASCT2 heterotrimers as a possible explanation for the previous misidentification of ASCT1 as a receptor for Syncytin-1. This redefinition of receptor specificity is important for proper understanding of Syncytin-1 function in normal and pathological pregnancy.
- MeSH
- antigeny CD98 - těžký řetězec MeSH
- fúze buněk * MeSH
- genové produkty env * metabolismus genetika MeSH
- lidé MeSH
- placenta * metabolismus MeSH
- těhotenské proteiny * metabolismus genetika MeSH
- těhotenství MeSH
- transportní systém ASC pro aminokyseliny * metabolismus genetika MeSH
- transportní systémy pro neutrální aminokyseliny metabolismus genetika MeSH
- trofoblasty metabolismus cytologie MeSH
- vedlejší histokompatibilní antigeny metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
STUDY QUESTION: Which actively translated maternal transcripts are differentially regulated between clinically relevant in vitro and in vivo maturation (IVM) conditions in mouse oocytes and zygotes? SUMMARY ANSWER: Our findings uncovered significant differences in the global transcriptome as well as alterations in the translation of specific transcripts encoding components of energy production, cell cycle regulation, and protein synthesis in oocytes and RNA metabolism in zygotes. WHAT IS KNOWN ALREADY: Properly regulated translation of stored maternal transcripts is a crucial factor for successful development of oocytes and early embryos, particularly due to the transcriptionally silent phase of meiosis. STUDY DESIGN, SIZE, DURATION: This is a basic science study utilizing an ICR mouse model, best suited for studying in vivo maturation. In the treatment group, fully grown germinal vesicle oocytes from stimulated ovaries were in vitro matured to the metaphase II (MII) stage either as denuded without gonadotropins (IVM DO), or as cumulus-oocyte complexes (IVM COC) in the presence of 0.075 IU/ml recombinant FSH (rFSH) and 0.075 IU/ml recombinant hCG (rhCG). To account for changes in developmental competence, IVM COC from non-stimulated ovaries (IVM COC-) were included. In vivo matured MII oocytes (IVO) from stimulated ovaries were used as a control after ovulation triggering with rhCG. To simulate standard IVM conditions, we supplemented media with amino acids, vitamins, and bovine serum albumin. Accordingly, in vitro pronuclear zygotes (IMZ) were generated by IVF from IVM DO, and were compared to in vivo pronuclear zygotes (IVZ). All experiments were performed in quadruplicates with samples collected for both polyribosome fractionation and total transcriptome analysis. Samples were collected over three consecutive months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All ICR mice were bred under legal permission for animal experimentation (no. MZE-24154/2021-18134) obtained from the Ministry of Agriculture of the Czech Republic. Actively translated (polyribosome occupied) maternal transcripts were detected in in vitro and in vivo matured mouse oocytes and zygotes by density gradient ultracentrifugation, followed by RNA isolation and high-throughput RNA sequencing. Bioinformatic analysis was performed and subsequent data validation was done by western blotting, radioactive isotope, and mitotracker dye labelling. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression analysis of acquired polysome-derived high-throughput RNA sequencing data revealed significant changes (RPKM ≥ 0.2; P ≤ 0.005) in translation between in vitro and in vivo matured oocytes and respectively produced pronuclear zygotes. Surprisingly, the comparison between IVM DO and IVM COC RNA-seq data of both fractionated and total transcriptome showed very few transcripts with more than a 2-fold difference. Data validation by radioactive isotope labelling revealed a decrease in global translation bof20% in IVM DO and COC samples in comparison to IVO samples. Moreover, IVM conditions compromised oocyte energy metabolism, which was demonstrated by both changes in polysome recruitment of each of 13 mt-protein-coding transcripts as well as by validation using mitotracker red staining. LARGE SCALE DATA: The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE241633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241633). LIMITATIONS, REASONS FOR CAUTION: It is extremely complicated to achieve in vivo consistency in animal model systems such as porcine or bovine. To achieve a high reproducibility of in vivo stimulations, the ICR mouse model was selected. However, careful interpretation of our findings with regard to assisted reproductive techniques has to be made by taking into consideration intra-species differences between the mouse model and humans. Also, the sole effect of the cumulus cells' contribution could not be adequately addressed by comparing IVM COC and IVM DO, because the IVM DO were matured without gonadotropin supplementation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirmed the inferiority of standard IVM technology compared with the in vivo approach. It also pointed at compromised biological processes employed in the critical translational regulation of in vitro matured MII oocytes and pronuclear zygotes. By highlighting the importance of proper translational regulation during in vitro oocyte maturation, this study should prompt further clinical investigations in the context of translation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Czech Grant Agency (22-27301S), Charles University Grant Agency (372621), Ministry of Education, Youth and Sports (EXCELLENCE CZ.02.1.01/0.0/0.0/15_003/0000460 OP RDE), and Institutional Research Concept RVO67985904. No competing interest is declared.
- MeSH
- choriogonadotropin farmakologie MeSH
- embryonální vývoj * fyziologie MeSH
- IVM techniky * MeSH
- kumulární buňky * metabolismus MeSH
- myši inbrední ICR * MeSH
- myši MeSH
- oocyty * metabolismus MeSH
- proteosyntéza MeSH
- transkriptom MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- zygota metabolismus MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. CONCLUSION: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.
- MeSH
- biologické markery krev MeSH
- chorioamnionitida krev diagnóza MeSH
- dospělí MeSH
- fetální krev metabolismus MeSH
- interleukin-6 * krev MeSH
- lidé MeSH
- placenta metabolismus MeSH
- placentární růstový faktor * krev MeSH
- plodová voda metabolismus MeSH
- předčasná porodní činnost * krev MeSH
- prediktivní hodnota testů * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Tubární potrat představuje vypuzení plodu z vejcovodu do dutiny břišní. Může být kompletní nebo nekompletní s rezidui přetrvávajícími ve vejcovodu. Jedná se o formu mimoděložního těhotenství, jejíž incidenci nelze přesně stanovit. Rozpoznání případů tubárního abortu je zásadní v péči o pacientku, protože může vést ke konzervativnějšímu přístupu. Diagnóza by měla být stanovena kombinací ultrazvukového vyšetření, hladiny b-hCG a peroperačního nálezu. Článek popisuje případ 30leté pacientky přijaté pro suspektní mimoděložní graviditu, kdy ultrazvukové vyšetření prokázalo masu připomínající tubární graviditu vedle dělohy a hladiny b-hCG byly 111,8 U/l. Peroperačně byl zjištěn tubární abort v Douglasově prostoru umožňující zachování obou vejcovodů. Histopatologický rozbor potvrdil klinickou diagnózu. Konzervativní přístup může mít dostatečný efekt v případě tubárního abortu, což umožňuje zachování fertility a tubárních funkcí.
Tubal abortion is characterized by the extrusion of the foetus into the abdominal (peritoneal) cavity. It can either be a complete extrusion or incomplete with residual tissue remaining in the fallopian tube. It is a type of ectopic pregnancy that is difficult to determine the exact incidence of tubal pregnancies. Identifying cases of tubal abortions is crucial for individualized care since it can lead to a more conservative treatment approach. The diagnosis should be based on ultrasound imaging, b-hCG levels and visual conformation during exploratory surgery, either open or laparoscopic. The article describes the case of a 30-year old patient who presented with lower abdominal pain and was admitted for a suspected ectopic pregnancy. Ultrasound imaging showed a mass resembling a tubal pregnancy next to the uterus with b-hCG levels of 111.8 U/L. During laparoscopic surgery, a tubal abortion was detected in the pouch of Douglas (Rectouterine pouch). This finding led us to preserve both fallopian tubes. Histopathology confirmed our clinical findings. A conservative approach can be sufficient in case of tubal abortions, which can lead to preserved fertility and tubal functions.
- MeSH
- dospělí MeSH
- Douglasův prostor diagnostické zobrazování patologie MeSH
- gynekologické chirurgické výkony metody MeSH
- laparoskopie MeSH
- lidé MeSH
- lidský choriogonadotropin, beta podjednotka analýza MeSH
- mimoděložní těhotenství * chirurgie diagnostické zobrazování patologie MeSH
- salpingektomie MeSH
- samovolný potrat * chirurgie diagnostické zobrazování patologie MeSH
- těhotenství MeSH
- ultrasonografie MeSH
- uterus diagnostické zobrazování patologie MeSH
- vejcovody chirurgie diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Sialic acids are negatively charged carbohydrates that are components of saccharide chains covalently linked to macromolecules. Sialylated glycoproteins are important for most biological processes, including reproduction, where they are associated with spermatogenesis, sperm motility, immune responses, and fertilization. Changes in the glycoprotein profile or sialylation in glycoproteins are likely to affect the quality of ejaculate. The aim of this study was to determine differences in the degree of sialylation between normozoospermic ejaculates and ejaculates with a pathological spermiogram using two lectins, Sambucus nigra (SNA) and Maackia amurensis (MAL II/MAA) recognizing α-2,6 or α-2,3 linkage of Sia to galactosyl residues. Our results show a close relationship between seminal plasma (SP) sialoproteins and the presence of anti-sperm antibodies in the ejaculate, apoptotic spermatozoa, and ejaculate quality. Using mass spectrometry, we identified SP sialoproteins such as, semenogelins, glycodelin, prolactin-inducible protein, lactotransferrin, and clusterin that are associated with spermatozoa and contribute to the modulation of the immune response and sperm apoptosis. Our findings suggest a correlation between the degree of SP glycoprotein sialylation and the existence of possible pathological states of spermatozoa and reproductive organs. Glycoproteins sialylation represents a potential parameter reflecting the overall quality of ejaculate and could potentially be utilised in diagnostics.
- MeSH
- analýza spermatu metody MeSH
- apoptóza MeSH
- ejakulace MeSH
- glykodelin metabolismus MeSH
- glykoproteiny metabolismus MeSH
- klusterin metabolismus MeSH
- kyseliny sialové metabolismus MeSH
- laktoferrin metabolismus MeSH
- lektiny metabolismus chemie MeSH
- lidé MeSH
- motilita spermií MeSH
- proteiny semenné plazmy metabolismus MeSH
- sekreční proteiny semenných váčků metabolismus MeSH
- sperma * metabolismus chemie MeSH
- spermie * metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. MATERIAL AND METHODS: This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians. RESULTS: Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. CONCLUSIONS: Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.
- MeSH
- amniocentéza MeSH
- biologické markery krev MeSH
- chorioamnionitida krev MeSH
- dospělí MeSH
- gestační stáří MeSH
- lidé MeSH
- placentární růstový faktor * krev MeSH
- plodová voda * mikrobiologie metabolismus MeSH
- předčasný odtok plodové vody * krev MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.
- MeSH
- biologické markery MeSH
- císařský řez MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- novorozenec MeSH
- placentární růstový faktor MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * diagnóza prevence a kontrola epidemiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
