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Reproduction, Fertility, and Development Oct 2019The involvement of the apoptosis signal-regulating kinase 1 (ASK1)-related signalling pathway in the control of reproduction is unknown. This study aimed to investigate...
The involvement of the apoptosis signal-regulating kinase 1 (ASK1)-related signalling pathway in the control of reproduction is unknown. This study aimed to investigate the role of ASK-1 in the control of basic ovarian functions (proliferation, apoptosis and hormone release) and its response to ovarian hormonal regulators (leptin and FSH). We compared the accumulation of ASK-1, proliferation marker proliferating cell nuclear antigen (PCNA), apoptosis marker Bax and apoptosis and proliferation regulating transcription factor p53 and the release of progesterone (P4), oxytocin (OT), insulin-like growth factor I (IGF-I) and prostaglandins F (PGF) and E (PGE) using cultured porcine ovarian granulosa cells transfected with ASK-1 cDNA and cultured with leptin or FSH. This study is the first to demonstrate that ASK-1 does not affect cell apoptosis and viability in ovarian cells, but promotes cell proliferation, suppresses p53, alters the release of ovarian hormones (P4, OT, IGF-I, PGF and PGE) and defines their response to the upstream hormonal regulators leptin and FSH. Therefore, ASK-1 can be considered a new and important regulator of multiple ovarian functions.
Topics: Animals; Cells, Cultured; Female; Follicle Stimulating Hormone; Gene Expression Regulation, Enzymologic; Insulin-Like Growth Factor I; Leptin; MAP Kinase Kinase Kinase 5; Ovary; Oxytocin; Progesterone; Prostaglandins E; Prostaglandins F; Swine
PubMed: 31217073
DOI: 10.1071/RD19055 -
Theriogenology Mar 2024Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper... (Review)
Review
Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper between two fundamental reproductive events - the estrous cycle and pregnancy. Uteroluteal research for the initial 33 years was productive but limited to laboratory species until the inclusion of farm animals in 1956. In the early 1960s, it was found that uterine luteolysin in sows travels unilaterally from a uterine horn to the adjacent CL which likely accounted for the heyday of uteroluteal research in the 1960s-70s. The luteolytic properties of PGF2α were demonstrated in rats in 1969. In 1971, (1) surgical separation of the lengthwise adherence between the uteroovarian vein and ovarian artery interfered with luteolysis in ewes, (2) species with primarily unilateral vs systemic uterine-induced luteolysis have a strong vs an absent or weak unilateral venoarterial transfer pathway, and (3) vascular infusions identified PGF2α as a uterine luteolysin. Vascular and PGF2α studies were beginning to merge. In 1973, a venoarterial pathway was firmly demonstrated in ewes and later in heifers by surgical anastomosis of a uterine vein or ovarian artery from a uterine-intact side to the corresponding vessel on the unilaterally hysterectomized side. More recent studies described how prostaglandins likely transfer through the walls of uterine and ovarian vessels using concentration gradients in sows and a prostaglandins transporter system in cows.
Topics: Pregnancy; Animals; Female; Cattle; Sheep; Swine; Rats; Guinea Pigs; Luteolysis; Dinoprost; Corpus Luteum; Uterus; Mammals
PubMed: 38266370
DOI: 10.1016/j.theriogenology.2024.01.014 -
Animal Reproduction Science Feb 2022In this study, aims were to evaluate orexin A (OXA) effects on mRNA abundance of important enzymes involved in prostaglandin production, such as cyclooxygenase 2...
Effects of orexin A on PTGS2, PTGES, CBR1 and PGFS mRNA transcript abundances and prostaglandin E and F concentrations in culture medium of pig uterine explants collected during early gestation and the estrogenic cycle.
In this study, aims were to evaluate orexin A (OXA) effects on mRNA abundance of important enzymes involved in prostaglandin production, such as cyclooxygenase 2 (PTGS2), microsomal PGE synthase-1 (PTGES), PGF synthase (PGFS) and carbonyl reductase 1 (CBR1), as well as prostaglandin E (PGE) and F (PGF) culture medium concentrations for endometrial and myometrial explants. Tissues were collected from gilts during specific phases of the estrogenic cycle or early gestational period. There were greater concentrations of PGE with OXA treatments of endometrial tissues collected on days 12-13 and 27-28, as well as PGF on days 10-11 of the gestational period. The PGF concentrations were less in tissues collected on days 27-28 of the gestational period. The OXA treatments resulted in lesser concentrations of PGE from myometrial tissues collected on days 10-11 and greater PGF on days 10-11 of the gestational period and 10-11 of the estrogenic cycle. Effects of OXA may occur due to actions at PTGS2, PTGES, PGFS and CBR1 genes because mRNA abundances for proteins encoded by these genes were affected by OXA. Results indicate there is an OXA effect on mRNA abundances and prostaglandin culture medium concentrations of uterine tissue collected at different stages of the gestational period or estrogenic cycle using different doses of OXA. It, therefore, is concluded OXA may affect de novo synthesis and secretion of PGE and PGF in the uterus of pigs.
Topics: Animals; Carbonyl Reductase (NADPH); Cyclooxygenase 2; Dinoprost; Dinoprostone; Endometrium; Female; Orexins; Pregnancy; Prostaglandins; RNA, Messenger; Swine; Uterus
PubMed: 34974394
DOI: 10.1016/j.anireprosci.2021.106910 -
Reproduction (Cambridge, England) Jan 2023Endometrial and luteal synthesis of prostaglandin F2alpha (PGF2A) occurs before and during luteolysis and is critical for luteal regression. This study demonstrates that...
IN BRIEF
Endometrial and luteal synthesis of prostaglandin F2alpha (PGF2A) occurs before and during luteolysis and is critical for luteal regression. This study demonstrates that PGF2A stimulates further PGF2A synthesis (autoamplification) apparently from the corpus luteum.
ABSTRACT
Understanding the endocrine profile of prostaglandin F2alpha (PGF2A) autoamplification is fundamental to comprehend luteal and endometrial responses to PGF2A. On day 10 of postovulation (preluteolysis), heifers (n = 6/group) were treated intrauterine with saline or PGF2A (0.5 mg; hour 0). A third group received flunixin meglumine + PGF (FM+PGF) to prevent endogenous synthesis of PGF2A. Exogenous PGF2A was metabolized at hour 2 as measured by PGF2A metabolite (PGFM). From hours 5 to 48, concentrations of PGFM were greatest in the PGF group, smallest in the FM+PGF, and intermediate in the control suggesting endogenous synthesis of PGF2A only in PGF group. Progesterone (P4) concentrations decreased transiently between hours 0 and 1 in PGF and FM+PGF groups but rebounded to pretreatment concentrations by hours 6 and 4, respectively. No control or FM+PGF heifers underwent luteolysis during the experimental period. Conversely, in the PGF group, one heifer had complete luteolysis (P4 < 1 ng/mL), two heifers had partial luteolysis followed by P4 and CL resurgence by hour 48, and three heifers did not undergo luteolysis. Endogenous PGF2A appears to be of luteal origin due to the lack of pulsatile pattern of PGFM and lack of endometrial upregulation of oxytocin receptor (typical of endometrial synthesis of PGF2A), whereas luteal downregulation of PGF receptor and HPGD indicates a classic luteal response to PGF2A signaling although other specific mechanisms were not investigated. The hypothesis was supported that a single PGF2A treatment simulating the peak of a natural luteolytic pulse and the uteroovarian transport of PGF2A stimulates measurable endogenous PGF2A production.
Topics: Cattle; Female; Animals; Dinoprost; Luteolysis; Corpus Luteum; Progesterone; Endometrium
PubMed: 36239920
DOI: 10.1530/REP-22-0242 -
The Journal of Veterinary Medical... May 2022Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are...
Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are metabolized into various lipid mediators. Lipid mediators such as prostaglandins (PGs) modulate inflammation and many of them are excreted into the urine. Thus, the investigation of the urinary lipid profile may reveal pathogenesis and help diagnosis of FIC. We collected urine samples from five FIC cats by spontaneous urination and analyzed 158 types of lipid mediators in urines using liquid chromatography-mass spectrometry. The urinary levels of PUFAs were higher in FIC compared to those of the healthy group. The excretions of a major inflammatory mediator, PGD, were less in FIC. Other well-known inflammatory mediators such as PGE, PGI, and their metabolites did not show a difference. In contrast, the levels of PGF and its 2 metabolites and PGF were higher in FIC. These results may provide new insights into the future management of cat FIC.
Topics: Animals; Cat Diseases; Cats; Chromatography, Liquid; Cystitis; Lipids; Mass Spectrometry; Prostaglandins F
PubMed: 35387958
DOI: 10.1292/jvms.22-0049 -
Cells Jun 2022Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid...
Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2α, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2α synthase abolished serum deprivation-induced LD suppression, LD-lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2α suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2α enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of β-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2α is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.
Topics: Animals; Autophagy; Dinoprost; Hepatocytes; Lipid Droplets; Prostaglandins; Zebrafish
PubMed: 35740999
DOI: 10.3390/cells11121870 -
Prostaglandins, Leukotrienes, and... Feb 2021Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F and prostaglandin...
Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F and prostaglandin F (PGF). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (Fam213b / Prxl2b) was accomplished by a two exon disruption. Prostamide F levels in wild type (WT) and PM/PGFS knock-out (KO) mice were determined by LC/MS/MS. Deletion of Fam213b (Prxl2b) had no observed effect on behavior, appetite, or fertility. In contrast, tonometrically measured intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. Outflow facility was measured in enucleated mouse eyes using the iPerfusion system. No effect on pressure dependent outflow facility occurred, which is consistent with the effects of prostamide F and PGF increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids known to raise intraocular pressure, namely prostaglandin D (PGD) and thromboxane A (TxA). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF and prostamide F to constrain the influence of those prostanoids that raise intraocular pressure.
Topics: Animals; Chromatography, Liquid; Dinoprost; Dinoprostone; Disease Models, Animal; Gene Deletion; Gene Knockout Techniques; Hydroxyprostaglandin Dehydrogenases; Intraocular Pressure; Male; Mice; Tandem Mass Spectrometry; Tonometry, Ocular
PubMed: 33418484
DOI: 10.1016/j.plefa.2020.102235 -
BMC Veterinary Research Jun 2023Difference in breed, nutrition status and climate in which animals are managed result in differences in response to reproductive hormones. Fertility rate to artificial...
Ovarian response and conception rate in Boran and Boran*Holstein cows treated by Gonadotrophin-realizing hormone and ProstaglandinF2α with and without exogenous progesterone.
BACKGROUND
Difference in breed, nutrition status and climate in which animals are managed result in differences in response to reproductive hormones. Fertility rate to artificial insemination is very low in Ethiopian Boran and Boran*Holstein crosses. This partly maybe due to adopting estrus and/or ovulation synchronization developed for temperate taurine cattle. Experimental study was conducted to evaluate ovarian response to combinations of Gonadotrophin-Realizing Hormone agonist (gonadorelin) and ProstaglandinF2α (PGF2α) with or without progesterone (Controlled Internal Drug Release/CIDR), and conception rate to timed AI. Postpartum native Ethiopian Boran (n = 60) and Boran*Holstein cross (n = 66) cows were randomly assigned to four treatment groups as Ovsynch (gonadorelin on day of start, PGF2α seven days later, 2nd gonadorelin at 48 h of PGF2α and insemination at 19 h of the 2nd gonadorelin); CIDR + Ovsynch (same as Ovsynch but CIDR device was inserted into vagina for 7 days); Cosynch (same as Ovsynch but insemination was made at the 2nd gonadorelin) and CIDR + Cosynch (same as Cosynch but CIDR was inserted for 7 days).
RESULT
There was no difference (P > 0.05) in ovulation rate to day 9 gonadorelin (88.33% in Boran; 78.79% in Boran*Holstein) and interval from day 9 gonadorelin to ovulation (36.5 ± 1.13 h in Boran and 36.057 ± 1.11 h in Boran*Holstein). Dominant follicle immediate to ovulation (14.95 ± 0.19 mm Vs 19.12 ± 0.49 mm) and corpus luteum size (16.31 ± 0.33 mm Vs 20.28 ± 0.43 mm ) respectively were smaller (P < 0.05) in Boran than Boran*Holstein. Plasma progesterone concentration at PGF2α was higher (P < 0.05) in Boran (11.91 ± 0.74ng/mL) than Boran*Holstein (6.13 ± 0.27ng/mL) but luteolysis rate was lower (P < 0.05) in Boran (87.9%) than Boran-Holstein (96.9%). Cows with CIDR had higher conception rate than cows without CIDR (72.00% Vs 39.02% in Boran*Holstein and 74.07%, Vs 51.52% in Boran respectively). Insemination at 19 h of gonadorelin administration resulted in higher conception rate (78.6% for Boran; 71.43% for Boran*Holstein) than insemination at gonadorelin (69.29% for Boran; 66.67% for Boran*Holstein).
CONCLUSION
Boran cows have smaller preovulatory follicles, smaller corpus luteum, large amount of progesterone and lower rate of luteolysis to PGF2α compared to Boran*Holstein. The CL of Boran cattle seems les reactive to PGF2α than Boran*Holstein CL. CIDR significantly improved conception rate in Boran and Boran*Holstein cows.
Topics: Female; Cattle; Animals; Progesterone; Dinoprost; Estrus Synchronization; Lactation; Gonadotropin-Releasing Hormone; Insemination, Artificial
PubMed: 37264362
DOI: 10.1186/s12917-023-03617-0 -
Reproduction in Domestic Animals =... Jan 2023Camelids have many unique reproductive features that considerably differ from those of other domestic species. Females are induced ovulators with subsequent development... (Review)
Review
Camelids have many unique reproductive features that considerably differ from those of other domestic species. Females are induced ovulators with subsequent development of a corpus luteum (CL) with a short lifespan. Plasma progesterone concentration starts to increase on day 4, peaks on day 8-9 and, in non-pregnant animals, basal concentration is reached around day 10-11 post-induction of ovulation. Luteolytic pulses of prostaglandin F (PGF ) are firstly detected on day 7 or 8 (approximately on day 5-6 after ovulation), with maximal luteolytic peaks observed between days 9 and 11 post-mating, in coincidence with a high endometrial expression of cyclooxygenase 2, a limiting enzyme in prostaglandins synthesis. Unlike other species, oxytocin seems not to be involved in the luteolytic process in these species. The CL is the main source of progesterone secretion, and its function is required to support pregnancy. Despite constant research efforts, aspects of reproduction and maternal recognition of pregnancy in camelids remain not fully understood. A transient decrease and subsequent recovery in plasma progesterone concentration are observed after day 9 post-mating in pregnant animals in association with a pulsatile release of PGF and a transitory decrease in CL vascularization. Thus, embryo recognition should occur between days 8 and 12 post-mating. In camels, conceptus tissues exhibit aromatizing activity with the capacity to synthesize large amounts of oestradiol. Similarly, llama blastocysts secrete oestradiol-17β during the preimplantation stage, with a higher production during the elongation period. An increase in the endometrial expression of oestrogen receptor α is also observed on day 12 post-mating. All these evidences suggest that oestrogen could be the signal released by the embryo at the time of its recognition in camelids. Besides, nearly 98% of pregnancies are carried out in the left horn. A decrease in the endometrial expression of mucin 1 and 16 genes has been reported, suggesting that these changes are crucial for successful embryo implantation; however, no differences have been observed between horns. Thus, maternal recognition of pregnancy in camelids is a particularly complex process that must occur in a concise time to allow the rescue of the CL and embryo survival.
Topics: Pregnancy; Female; Animals; Luteolysis; Progesterone; Corpus Luteum; Estradiol; Endometrium; Camelids, New World; Dinoprost
PubMed: 36149369
DOI: 10.1111/rda.14269 -
International Journal of Environmental... May 2020Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with... (Review)
Review
Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPA- or organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Child; Cross-Sectional Studies; Dinoprost; Female; Follow-Up Studies; Humans; Infant, Newborn; Male; Oxidative Stress; Phenols; Pregnancy; Prospective Studies; Single-Blind Method; Young Adult
PubMed: 32455625
DOI: 10.3390/ijerph17103609