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Animal Reproduction Science Apr 2022Aim of this study was to determine the effect of metritis on in-vitro uterine contractility. Uteri obtained from 16 euthanized Holstein-Friesian cows were divided into...
Aim of this study was to determine the effect of metritis on in-vitro uterine contractility. Uteri obtained from 16 euthanized Holstein-Friesian cows were divided into two groups depending on whether metritis was absent (M-, n = 6) or present (M+, n = 10). Four longitudinal and four circular myometrial strips of all uteri were incubated in an organ bath. Spontaneous contractility was recorded in five consecutive 30-minute periods (T1-T5). This was followed by stimulation of one longitudinal and one circular strip with increasing concentrations of oxytocin, prostaglandinF (PGF), and calcium chloride (each during four 30-minute periods [T6-T9]). Strips in group M+ had higher minimum amplitude (minA) values at T1 and higher minA, mean amplitude (meanA), and area under the curve (AUC) values at T2 than strips in group M- (P ≤ 0.05). In the M+ group, the maximum amplitude (maxA), meanA, and AUC values of circular strips were higher than those of longitudinal strips during spontaneous contractility (T1, T4, and T5; P ≤ 0.05). The minA, meanA, and AUC values for strips in group M+ were higher than those in group M- when exposed to the highest concentration of PGF (P ≤ 0.05). During stimulation with PGF (T9), longitudinal strips had higher maxA values than the circular strips in group M+ (P ≤ 0.05). Spontaneous and stimulated contractility were temporarily increased in uteri with metritis compared to healthy uteri. Both myometrial layers, especially in uteri with metritis, reacted differently during spontaneous contractility and to stimulation with PGF.
Topics: Animals; Cattle; Female; Myometrium; Oxytocin; Postpartum Period; Prostaglandins F; Uterine Contraction; Uterus
PubMed: 35339982
DOI: 10.1016/j.anireprosci.2022.106971 -
Ageing Research Reviews Feb 2022The association between F-isoprostanes and Alzheimer's disease (AD) has been controversially discussed in the literature since the 1990s. However, no systematic review... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The association between F-isoprostanes and Alzheimer's disease (AD) has been controversially discussed in the literature since the 1990s. However, no systematic review has been performed so far.
METHODS
A systematic review of observational studies on the associations of F-isoprostanes and the specific biomarker 8-iso-prostaglandin F with AD were conducted. Random-effects model meta-analyses were performed.
RESULTS
29 studies were included in the systematic review, including four longitudinal studies. In an overall meta-analysis of the 25 cross-sectional studies, F-isoprostane levels were statistically significantly associated with AD (Hedge's g [95% confidence interval]: 1.00 [0.69-1.32]). When studies were grouped by biomarker and sample specimen, F-isoprostane and 8-iso-prostaglandin F levels were statistically significantly elevated in tissue samples of the frontal lobe of AD patients. Moreover, F-isoprostane levels in cerebrospinal fluid and 8-iso-prostaglandin F levels in blood samples of AD patients were significantly increased. Meta-analyses of the few longitudinal studies did not reach statistical significance.
DISCUSSION
Increased concentrations of F-isoprostanes were found in AD patients. However, due to the lack of adjustment in most cross-sectional case-control studies, results must be interpreted carefully. In addition, the causality of the association is uncertain because evidence from well-conducted longitudinal studies was conflicting, and further longitudinal studies are required to reinforce the results.
Topics: Alzheimer Disease; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Humans; Isoprostanes; Oxidative Stress
PubMed: 34954419
DOI: 10.1016/j.arr.2021.101552 -
Paediatric Respiratory Reviews Sep 2015Asthma represents the most common chronic respiratory disease of childhood. Its current standard diagnosis relies on patient history of symptoms and confirmed expiratory... (Review)
Review
Asthma represents the most common chronic respiratory disease of childhood. Its current standard diagnosis relies on patient history of symptoms and confirmed expiratory airflow limitation. Nevertheless, the spectrum of asthma in clinical presentation is broad, and both symptoms and lung function may not always reflect the underlying airway inflammation, which can be determined by different pathogenetic mechanisms. For these reasons, the identification of objective biomarkers of asthma, which may guide diagnosis, phenotyping, management and treatment is of great clinical utility and might have a role in the development of personalized therapy. The availability of non-invasive methods to study and monitor disease inflammation is of relevance especially in childhood asthma. In this sense, a promising role might be played by the measurement of exhaled biomarkers, such as exhaled nitric oxide (FE(NO)) and molecules in exhaled breath condensate (EBC). Furthermore, recent studies have shown encouraging results with the application of the novel metabolomic approach to the study of exhaled biomarkers. In this paper the existing knowledge in the field of asthma biomarkers, with a special focus on exhaled biomarkers, will be highlighted.
Topics: Aldehydes; Asthma; Biomarkers; Breath Tests; Child; Dinoprost; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Inflammation; Leukotrienes; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress
PubMed: 26100359
DOI: 10.1016/j.prrv.2015.05.001 -
Molecular Reproduction and Development Jul 2023Pregnancy establishment in mammals, including pigs, requires coordinated communication between developing conceptuses (embryos with associated membranes) and the... (Review)
Review
Pregnancy establishment in mammals, including pigs, requires coordinated communication between developing conceptuses (embryos with associated membranes) and the maternal organism. Porcine conceptuses signalize their presence by secreting multiple factors, of which estradiol-17β (E2) is considered the major embryonic signal initiating the maternal recognition of pregnancy. During this time, a limited supply of prostaglandin (PGF2α) to the corpora lutea and an increased secretion of luteoprotective factors (e.g., E2 and prostaglandin E2 [PGE2]) lead to the corpus luteum's maintained function of secreting progesterone, which in turn primes the uterus for implantation. Further, embryo implantation is related to establishing an appropriate proinflammatory environment coordinated by the secretion of proinflammatory mediators including cytokines, growth factors, and lipid mediators of both endometrial and conceptus origin. The novel, dual role of PGF2α has been underlined. Recent studies involving high-throughput technologies and sophisticated experimental models identified a number of novel factors and revealed complex relationships between these factors and those already established. Hence, it seems that early pregnancy should be regarded as a sequence of processes orchestrated by pleiotropic factors that are involved in redundancy and compensatory mechanisms that preserve the essential functions critical for implantation and placenta formation. Therefore, establishing the hierarchy between all molecules present at the embryo-maternal interface is now even more challenging.
Topics: Pregnancy; Female; Animals; Swine; Dinoprost; Pregnancy, Animal; Embryo Implantation; Prostaglandins; Dinoprostone; Mammals
PubMed: 35385215
DOI: 10.1002/mrd.23567 -
Frontiers in Endocrinology 2023Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in...
INTRODUCTION
Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.
METHODS
Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.
RESULTS
The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.
DISCUSSION
In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.
Topics: Infant, Newborn; Female; Humans; Dinoprost; NF-kappa B; Calcium; Premature Birth; Cyclooxygenase 2; Myometrium; Inflammation; Obstetric Labor, Premature; Cytokines; RNA, Messenger
PubMed: 37547305
DOI: 10.3389/fendo.2023.1150125 -
The Journal of Veterinary Medical... Sep 2021We determined a comprehensive immunohistochemistry of putative isoforms of enzymes for prostaglandin (PG) Fα and PGE biosynthesis and these PGs levels in placenta and...
Prostaglandins Fα and E in rat placenta and fetal membrane: a comprehensive immunohistochemistry of their synthetic enzymes and in vivo tissue levels during normal pregnancy.
We determined a comprehensive immunohistochemistry of putative isoforms of enzymes for prostaglandin (PG) Fα and PGE biosynthesis and these PGs levels in placenta and fetal membrane of normal pregnant rats in vivo. Placenta and fetal membrane showed positive immunoreactions for phospholipase A group 4A, but not group 2A, and cyclooxygenase (COX)-1 rather than COX-2. They showed positive immunoreactions for at least one isoform of each of PGF synthase and PGE synthase with tissue-dependent variations. PGFα and PGE levels in both tissues were highest on day 12 and declined and remained low thereafter. Obtained data would be the basic information on the primary PGs synthesis in rat placenta and fetal membrane in normal pregnancy.
Topics: Animals; Cyclooxygenase 2; Dinoprost; Extraembryonic Membranes; Female; Immunohistochemistry; Placenta; Pregnancy; Prostaglandins; Prostaglandins F; Rats
PubMed: 34334510
DOI: 10.1292/jvms.21-0183 -
Reproduction in Domestic Animals =... Sep 2023Canine pregnancy relies on luteal steroidogenesis for progesterone (P4) production. The canine placenta responds to P4, depending on the nuclear P4 receptor (PGR). This... (Review)
Review
Canine pregnancy relies on luteal steroidogenesis for progesterone (P4) production. The canine placenta responds to P4, depending on the nuclear P4 receptor (PGR). This has sparked interest in investigating the interaction between ovarian luteal steroids and the placenta in dogs. Canine placentation is characterized by restricted (shallow) trophoblast invasion, making the dog an interesting model for studying decidua-derived modulation of trophoblast invasion, compared with the more invasive (hemochorial) placentation. The PGR is expressed in maternally derived decidual cells and plays a crucial role in feto-maternal communication during pregnancy maintenance. Understanding PGR-mediated signalling has clinical implications for improving reproductive performance control in dogs. Altering the PGR signalling induces the release of PGF2α from the foetal trophoblast, hindering placental homeostasis, which can also be achieved with antigestagens like aglepristone. Consequently, luteolysis, both natural and antigestagen-induced, involves apoptosis, vascular lesion, and immune cell infiltration in the placenta, resulting in placentolysis and foetal membranes expulsion. Our laboratory developed the immortalized dog uterine stromal (DUS) cell line to study canine-specific decidualization. We study canine reproduction by observing physiological processes and investigating evidence-based mechanisms of decidualization and feto-maternal interaction. Our focus on morphology, function and molecular aspects enhances understanding and enables targeted and translational studies.
Topics: Female; Pregnancy; Dogs; Animals; Placenta; Ovary; Apoptosis; Corpus Luteum; Dinoprost
PubMed: 37724655
DOI: 10.1111/rda.14443 -
British Journal of Pharmacology Apr 2019In contrast to the availability of potent and selective antagonists of several prostaglandin receptor types (including DP , DP , EP and TP receptors), there has been a... (Review)
Review
In contrast to the availability of potent and selective antagonists of several prostaglandin receptor types (including DP , DP , EP and TP receptors), there has been a paucity of well-characterized, selective FP receptor antagonists. The earliest ones included dimethyl amide and dimethyl amine derivatives of PGF , but these have failed to gain prominence. The fluorinated PGF analogues, AL-8810 and AL-3138, were subsequently discovered as competitive and non-competitive FP receptor antagonists respectively. Non-prostanoid structures, such as the thiazolidinone AS604872, the D-amino acid-based oligopeptide PDC31 and its peptidomimic analogue PDC113.824 came next, but the latter two are allosteric inhibitors of FP receptor signalling. AL-8810 has a sub-micromolar in vitro potency and ≥2 log unit selectivity against most other PG receptors when tested in several cell- and tissue-based functional assays. Additionally, AL-8810 has demonstrated therapeutic efficacy as an FP receptor antagonist in animal models of stroke, traumatic brain injury, multiple sclerosis, allodynia and endometriosis. Consequently, it appears that AL-8810 has become the FP receptor antagonist of choice. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
Topics: Animals; Dinoprost; Drug Discovery; Humans; Prostaglandins F, Synthetic; Receptors, Prostaglandin
PubMed: 29679483
DOI: 10.1111/bph.14335 -
Free Radical Biology & Medicine Feb 2018Oxidative stress is one hypothesized mechanism linking anthropometric, behavioral, and medical risk factors with cardiovascular disease (CVD). We evaluated...
Oxidative stress is one hypothesized mechanism linking anthropometric, behavioral, and medical risk factors with cardiovascular disease (CVD). We evaluated cross-sectional associations between CVD risk factors and biomarkers of oxidative stress, and investigated these biomarkers as predictors of incident diabetes and hypertension among premenopausal women. F-isoprostane (F-IsoP) and metabolite (15-F-IsoP-M), reliable biomarkers of oxidative stress, were measured in urine samples collected at enrollment from 897 premenopausal women (ages 35-54) enrolled in the Sister Study cohort without a CVD history. Blood pressure, waist circumference, and body mass index (BMI) were measured at enrollment by trained study personnel. Diabetes and cigarette smoking were self-reported via enrollment questionnaires. Over a maximum follow-up of 11.5 years, participants self-reported incident diabetes and hypertension diagnoses on mailed questionnaires. In cross-sectional analyses, both F-IsoP and 15-F-IsoP-M were positively associated with BMI, waist circumference, diastolic blood pressure, and current smoking. F-IsoP was elevated among those with diabetes, and 15-F-IsoP-M increased with higher systolic blood pressure. Prospective analyses suggested an increased hypertension risk among those with elevated 15-F-IsoP-M (highest vs. lowest quartile: hazard ratio=2.34; 95% CI: 1.20-4.56). Our results suggest that urinary F-IsoP and 15-F-IsoP-M are positively associated with adiposity measures, blood pressure, and cigarette smoking. Further investigation is warranted to evaluate 15-F-IsoP-M as a predictor of hypertension.
Topics: Adult; Aged; Biomarkers; Biometry; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Female; Follow-Up Studies; Humans; Middle Aged; Oxidative Stress; Predictive Value of Tests; Premenopause; Prognosis; Risk Factors; United States
PubMed: 29229550
DOI: 10.1016/j.freeradbiomed.2017.12.006 -
Veterinary Research Communications Dec 2022To determine the effect of the combination of melatonin implants and prostaglandin (PG) F2α on reproductive performance in the late breeding season (Dec at the northern...
To determine the effect of the combination of melatonin implants and prostaglandin (PG) F2α on reproductive performance in the late breeding season (Dec at the northern hemisphere), 500 Lacaune ewes were divided into four groups. On day 0 (7 Nov), 150 ewes were treated with a melatonin (M) implant. From that group, 64 ewes (M + 1PGF group) were injected with 10-mg prostaglandin (PG) F2α 34 d after melatonin implantation (11 Dec). The remaining 86 ewes (M group) were treated with melatonin, only. Another group of 75 ewes (2PGF group) was treated with double injection of PGF2α (9 days between the first and second application) (2 and 11 Dec), and 75 non-treated ewes (C group) were the control group. The remaining 200 ewes of the flock were not considered in the study. Rams (n = 23) were introduced on 11 Dec. The percentage of prolificacy, lambing and fecundity rates were calculated. Lambing rate did not differ among groups (M: 79%; M + 1PGF: 78%; 2PGF: 69%; C: 71%). The M + 1PGF group had a higher % of prolificacy than the 2PGF group (P < 0.10) and the C group (P = 0.06) (M: 1.65 ± 0.07; M + 1PGF: 1.74 ± 0.09; 2PGF: 1.54 ± 0.08; C: 1.54 ± 0.07 lambs/lambing) (P < 0.05), and a higher fecundity than the 2PGF group (P < 0.05) and the C group (P < 0.10) (M: 1.30 ± 0.09; M + 1PGF: 1.36 ± 0.11; 2PGF: 1.07 ± 0.10; C: 1.08 ± 0.09 lambs/ewe). Ewes implanted with melatonin had significantly higher prolificacy (1.69 ± 0.06 lambs/lambing) (P < 0.05) and fecundity (1.33 ± 0.07 lambs/ewe) (P = 0.01) than did ewes that did not receive melatonin (1.54 ± 0.04 and 1.08 ± 0.04, resp.). In conclusion, melatonin implants increased the number of lambs born per ewe in a late-autumn mating season, and the effect was greatest if it was given in combination with PGF2α administration at ram introduction.
Topics: Sheep; Animals; Female; Seasons; Dinoprost; Melatonin; Reproduction; Prostaglandins
PubMed: 36018475
DOI: 10.1007/s11259-022-09990-9