Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment. Analyses of APS placentas showed a reduced cell proliferation, lower protein content and thinning of endothelial cells. Disturbances in APS trophoblast cells were linked to a cell cycle shift in cytotrophoblast cells, and a reduced number of spiral artery-associated trophoblast giant cells (SpA-TGC). Transcriptomic profiling of placental tissue highlighted disruptions in cell cycle regulation with notable downregulation of genes involved in developmental or signaling processes. Cellular senescence, metabolic and p53-related pathways were also enriched, suggesting potential mechanisms underlying placental dysfunction in APS. Thrombotic events, though occasionally detected, appeared to have no significant impact on the overall pathological changes. The increased number of dysfunctional uNK cells was not associated with enhanced cytotoxic capabilities. Transcriptomic data corroborated these findings, showing prominent suppression of NK cell secretory capacity and cytokine signaling pathways. Our study highlights the multifactorial nature of APS-associated placental pathologies, which involve disrupted angiogenesis, cell cycle regulation, and NK cell functionality.
- MeSH
- antifosfolipidový syndrom * imunologie patologie MeSH
- buňky NK * imunologie metabolismus MeSH
- modely nemocí na zvířatech * MeSH
- myši MeSH
- placenta * metabolismus patologie MeSH
- proliferace buněk MeSH
- stanovení celkové genové exprese MeSH
- těhotenství MeSH
- transkriptom MeSH
- trofoblasty metabolismus patologie imunologie MeSH
- uterus * patologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.
- MeSH
- endometrium metabolismus MeSH
- gastrointestinální motilita MeSH
- lidé MeSH
- progesteron * metabolismus farmakologie MeSH
- receptory progesteronu * genetika metabolismus MeSH
- těhotenství MeSH
- uterus metabolismus MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Aquaporin proteins (AQPs) are a family of channels expressed in numerous mammalian tissues, where they play a fundamental role in regulating water transport across cell membranes. Based on reports that AQPs are present in the reproductive system and participate in reproductive processes, our aim was to investigate the effect of progesterone (P(4)), estradiol (E(2)), oxytocin (OT), arachidonic acid (AA), forskolin (FSK) and cyclic adenosine monophosphate (cAMP) on AQP1 and AQP5 expression at mRNA and protein levels in porcine uterine explants from Days 14-16 of gestation in order to determine if they play a role in implantation period in pigs. Quantitative real time PCR and Western-blot analysis revealed that the uterine explants treated with FSK and cAMP produce delayed, but long-term effects on AQP1 abundance (24 h) while AQP5 had a rapid and sustained response to FSK and cAMP in protein content (3 and 24 h). AA increases gene and protein content of AQP1 after longer exposition whereas AQP5 increases after 3 h only at the protein level. Both AQPs potentially remains under control of steroid hormones. OT has been shown to increase AQP1, and decrease AQP5 mRNA, without visible changes in protein content. P(4), E(2), AA, FSK and cAMP caused the appearance of AQP5 expression in the basolateral plasma membrane of the epithelial cells. The staining represents most likely AQP5 functioning mechanism for both absorption and reabsorption across the glandular epithelium.
- MeSH
- akvaporin 1 metabolismus MeSH
- akvaporin 5 metabolismus MeSH
- AMP cyklický metabolismus MeSH
- estradiol metabolismus MeSH
- implantace embrya * MeSH
- imunohistochemie MeSH
- kolforsin metabolismus MeSH
- kyselina arachidonová metabolismus MeSH
- oxytocin metabolismus MeSH
- prasata MeSH
- progesteron metabolismus MeSH
- techniky in vitro MeSH
- těhotenství MeSH
- uterus metabolismus MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
One of the most abundant immunologic cell types in early decidua is the uterine natural killer (UNK) cell that despite the presence of cytoplasmic granules rich in perforin and granzymes does not degranulate in normal pregnancy. UNK cells are important producers of angiogenic factors that permit normal dilation of uterine arteries to provide increased blood flow for the growing feto-placental unit. Gram-negative bacteria lipopolysaccharide (LPS) administration can trigger an imbalance of pro-inflammatory and anti-inflammatory cytokines impairing the normal immune cells activity as well as uterine homeostasis. The present study aimed to evaluate by immunohistochemistry the reactivity of perforin and alpha-actin on UNK cell from LPS-treated pregnant mice. For the first time, we demonstrate that LPS injection in pregnant mice causes alpha-actin down regulation, concomitantly with perforin loss in UNK cells. This suggests that LPS alters UNK cell migration and activates cytotoxic granule release.
- MeSH
- aktiny metabolismus MeSH
- buňky NK účinky léků metabolismus MeSH
- down regulace účinky léků MeSH
- lipopolysacharidy farmakologie MeSH
- myši MeSH
- perforin metabolismus MeSH
- těhotenství MeSH
- uterus účinky léků metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
V rámci naší práce jsme se zabývali vyšetřením plodové vody u pacientek s diagnózou předčasného předtermínového odtoku plodové vody (PPROM). Nalezení metody vyšetření plodové vody schopné co nejčasnější detekce intraamniální zánětlivé reakce, která by nepovšimnuta mohla poškodit a v nejzávažnějších případech až ohrozit na životě plod nebo matku, považujeme za jeden z nejdůležitějších úkolů současné fetomaternální medicíny. To byl i hlavní důvod, proč jsme si ke svému výzkumu zvolili toto téma. Zajímal nás nejen již známý interleukin-6 (IL-6), ale k vyšetření plodové vody jsme přistoupili komplexněji. Použili jsme tzv. cytologicko-energetický princip doplněný o vyšetření aspartátamino-transferázy (AST), s kterým jsou již dlouhodobé zkušenosti při vyšetřování jiných extracelulárních tekutin. Sledovali jsme hodnoty C-reaktivního proteinu (CRP) a leukocytů v séru matky, IL-6, AST a koeficient energetické bilance (KEB) v plodové vodě a zjišťovali, které imunokompetentní buňky dominují v plodové vodě při různých typech zánětlivé reakce. Podle výsledků vyšetření kontrolní kohorty pacientek byla nutná korekce hranice normy u KEB oproti normám u jiných extracelulárních tekutin. Přestože naše studie zahrnuje zatím jen 44 pacientek, z toho 21 kontrol a 23 vyšetřovaných, již z takto malého počtu lze vysledovat určité tendence změn pozorovaných parametrů. Za důležité považujeme zjištění, že KEB, AST a cytologické vyšetření jsou metody pro predikci intraamniálního zánětu stejně spolehlivé a zároveň méně finančně náročné než vyšetření IL-6, a tím i vhodnější pro využití v menších nemocnicích či rozvojových zemích. V naší studii pokračujeme dále s cílem potvrdit dosud zjištěné trendy na větším počtu pacientek.
In our study we have dealt with the amniotic fluid examination on female patients with diagnosis of preterm premature rupture of membranes (PPROM). For one of the most important task in the feto-maternal medicine we consider the discovered method of amniotic fluid examination which is capable of the earliest possible detection in an intraamniotic inflammatory response. Unnoticed could harm or in the most serious cases threat the life of fetus or its mother. This was also the main reason why we chose this topic for our study. We have not been interested only in already known interleukin-6 (IL-6), but we have approached the examination comprehensively. We used the cytological-energetic principle supplemented by the examination of aspartate-amino-transferase (AST), in which already are long-term experiences in investigating other extracellular fluids. We have monitored values of C-reactive protein (CRP) and leucocytes in maternal serum, IL-6, AST and energetic score ratio (KEB) in amniotic fluid. Further we have investigated which imunocompetent cells have been dominant in amniotic fluid at different types of inflamantory reaction. According to the results of the examination of the control groups, it was necessary to correct the KEB limit in comparison to KEB limits of other extracellular fluids. Although our study includes untill now only 44 patients - 21 controls and 23 investigated persons, we have been already able to find out some trends of changes in observed parametres. As a very impotant discovery we consider the fact, that KEB, AST and cytological examination of amniotic fluid seem to be the methods for prediction of chorioamnionitis as reliable as the examination of IL-6. These methods are besides less expensive and therefore more suitable for the use in the small hospitals and developing countries. We continue in our study to confirm the previously found trends on the larger numbers of patients.
- Klíčová slova
- koeficient energetické bilance, KEB,
- MeSH
- amniocentéza MeSH
- aspartátaminotransferasy MeSH
- biochemická analýza krve MeSH
- C-reaktivní protein MeSH
- dospělí MeSH
- energetický metabolismus MeSH
- Klebsiella pneumoniae izolace a purifikace MeSH
- kompartmenty tělních tekutin MeSH
- komplikace těhotenství MeSH
- leukocyty MeSH
- lidé MeSH
- lymfocyty MeSH
- plodová voda * cytologie MeSH
- předčasný odtok plodové vody * diagnóza etiologie patologie MeSH
- těhotenství MeSH
- uterus metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Very little is known about the occurrence of immune system cells in the canine uterus. The aim of this study was to generate information about lymphocyte subsets that are present in the healthy canine uterus and that are recruited under inflammatory conditions caused by pyometra. Using immunohistochemistry and flow cytometry, a significant influx of γδ T lymphocytes was found in pyometra samples mainly due to recruitment of γδ(+)/CD8(-) T lymphocytes. The relative expression of genes encoding selected cytokines/chemokines was evaluated in samples from healthy and pyometra-affected uteri. Expression of pro-inflammatory cytokines (including IL-1β, TNF-α, IL-8, IL-17 and IFN-γ) and chemokines (including CXCL10, CCL4 and CCL5) was upregulated in pyometra samples confirming the presence of inflammation. In contrast, the expression of the homeostatic chemokine CCL25 and of the anti-inflammatory cytokine IL-10 was downregulated and unchanged, respectively.
- MeSH
- chemokiny genetika imunologie metabolismus MeSH
- cytokiny genetika imunologie metabolismus MeSH
- imunohistochemie veterinární MeSH
- kvantitativní polymerázová řetězová reakce veterinární MeSH
- nemoci psů imunologie metabolismus MeSH
- průtoková cytometrie veterinární MeSH
- psi genetika imunologie metabolismus MeSH
- pyometra imunologie metabolismus veterinární MeSH
- regulace genové exprese MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- uterus imunologie metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- psi genetika imunologie metabolismus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Polycyclic aromatic hydrocarbons (PAHs) are an important group of environmental pollutants, known for their mutagenic and carcinogenic activities. Many PAHs are aryl hydrocarbon receptor (AhR) ligands and several recent studies have suggested that PAHs or their metabolites may activate estrogen receptors (ER). The present study investigated possible estrogenic/antiestrogenic effects of abundant environmental contaminants benzo[a]pyrene (BaP), benz[a]anthracene (BaA), fluoranthene (Fla) and benzo[k]fluoranthene (BkF) in vivo, using the immature rat uterotrophic assay. The present results suggest that BaA, BaP and Fla behaved as estrogen-like compounds in immature Wistar rats, when applied for 3 consecutive days at 10mg/kg/day, as documented by a significant increase of uterine weight and hypertrophy of luminal epithelium. These effects were likely to be mediated by ERalpha, a major subtype of ER present in uterus, as they were inhibited by treatment with ER antagonist ICI 182,780. BaA, the most potent of studied PAHs, induced a significant estrogenic effect within a concentration range 0.1-50mg/kg/day; however, it did not reach the maximum level induced by reference estrogens. The proposed antiestrogenicity of the potent AhR agonist BkF was not confirmed in the present in vivo study; the exposure to BkF did not significantly affect the uterine weight, although a weak suppression of ERalpha immunostaining was observed in luminal and glandular epithelium, possibly related to its AhR-mediated activity. The PAHs under study did not induce marked genotoxic damage in uterine tissues, as documented by the lack of Ser-15-phoshorylated p53 protein staining. With the exception of Fla, all three remaining compounds increased CYP1-dependent monooxygenation activities in liver at the doses used, suggesting that the potential tissue-specific antiestrogenic effects of PAHs mediated by metabolization of 17beta-estradiol also cannot be excluded. Taken together, these environmentally relevant PAHs induced estrogenic effects in vivo, which might affect their toxic impact and carcinogenicity.
- MeSH
- alfa receptor estrogenů metabolismus MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- endokrinní disruptory toxicita MeSH
- epitel účinky léků MeSH
- estradiol metabolismus MeSH
- estrogeny biosyntéza MeSH
- financování organizované MeSH
- fosforylace MeSH
- hydroxylace MeSH
- imunohistochemie MeSH
- jaterní mikrozomy metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- látky znečišťující životní prostředí toxicita MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- ovarium účinky léků MeSH
- polycyklické aromatické uhlovodíky toxicita MeSH
- potkani Wistar MeSH
- uterus metabolismus účinky léků MeSH
- velikost orgánu účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- MeSH
- alanintransaminasa krev MeSH
- biochemická analýza krve MeSH
- kadmium metabolismus MeSH
- králíci MeSH
- otrava kadmiem krev metabolismus MeSH
- ovarium metabolismus MeSH
- testis metabolismus MeSH
- uterus metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
