PGF2 Research Articles

Studies on in vivo antithrombotic activity of quercetin, a natural flavonoid isolated from a traditional medicinal plant, African eggplant (Solanum indicum)

Ethnopharmacological relevanceEvery year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. Aim of the studyThis study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. Materials and methodsBioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. ResultsQC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 μM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 μM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). ConclusionEffective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.

A pheromone receptor in cichlid fish mediates attraction to females but inhibits male parental care

Reproductive behaviors differ across species, but the mechanisms that control variation in mating and parental care systems remain unclear. In many animal species, pheromones guide mating and parental care. However, it is not well understood how vertebrate pheromone signaling evolution can lead to new reproductive behavior strategies. In fishes, prostaglandin F2α (PGF2α) drives mating and reproductive pheromone signaling in fertile females, but this pheromonal activity appears restricted to specific lineages, and it remains unknown how a female fertility pheromone is sensed for most fish species. Here, we utilize single-cell transcriptomics and CRISPR gene editing in a cichlid fish model to identify and test the roles of key genes involved in olfactory sensing of reproductive cues. We find that a pheromone receptor, Or113a, detects fertile cichlid females and thereby promotes male attraction and mating behavior, sensing a ligand other than PGF2α. Furthermore, while cichlid fishes exhibit extensive parental care, for most species, care is provided solely by females. We find that males initiate mouthbrooding parental care if they have disrupted signaling in ciliated sensory neurons due to cnga2b mutation or if or113a is inactivated. Together, these results show that distinct mechanisms of pheromonal signaling drive reproductive behaviors across taxa. Additionally, these findings indicate that a single pheromone receptor has gained a novel role in behavior regulation, driving avoidance of paternal care among haplochromine cichlid fishes. Lastly, a sexually dimorphic, evolutionarily derived parental behavior is controlled by central circuits present in both sexes, while olfactory signals gate this behavior in a sex-specific manner.

Associations among the largest follicle, preovulatory estradiol concentrations, and predominant vaginal epithelial cells at the completion of hormonal ovarian stimulation for fixed-time artificial insemination in goats.

The objective of the present study was to investigate the association among the largest follicle (LF), preovulatory estradiol (E2), and predominant vaginal epithelial cell at the completion of hormonal ovarian stimulation for fixed-time artificial insemination (FTAI) in goats. Thirty-seven crossbred Boer does received gonadotropin-releasing hormone (GnRH) and intravaginal progesterone (P4)-releasing devices (day 0). On day 5, P4 devices were removed and does received prostaglandin F2α and equine chorionic gonadotrophin. On day 7, does received GnRH, and FTAI was undertaken. On day 7, does were divided into three groups, i.e. small-sized (3-3.9 mm; n = 5), medium-sized (4-4.9 mm; n = 8), and large-sized (≥5 mm; n = 24) according to the diameter of the ovarian LF; follicular characteristics (number and diameter) were identified, and blood samples and vaginal smears were collected. The average diameters of total antral follicles and LF and the percentage of superficial cell were greatest in large-sized LF does (p < .01). The average diameters of total antral follicle (r = .68) and LF (r = .71), number of preovulatory follicle (r = .58), and plasma E2 concentrations (r = .61) were positively correlated with the percentage of superficial cells (p < .01). The likelihood of a pregnancy outcome after the FTAI increased by 13.71 times in does with a greater average diameter of antral follicle, 14.18 times with emergence of a large preovulatory follicle, and 36.83 times with a higher percentage of vaginal superficial cells (p < .01). It was concluded that there is a relationship between the cell types of the vaginal epithelium, the diameters of the largest ovarian follicles, and the concentration of E2 in goats subjected to FTAI protocols.

Impact of Estrus Response and Pregnancy Rate of Two Cows That are Injected with Prostaglandin F2α Hormone in the System Maintenance is Different to Livestock Farming

Livestock farming is an effort to breed livestock to obtain benefits or results in the form of products and income. The success of a livestock business depends on three elements commonly referred to as the production triangle, namely seeds, feed, and management. In addition, the techno-socioeconomic characteristics of livestock farmers greatly influence the development of livestock businesses and will later affect the income of livestock farmers. The aim of the research was to examine the injection of the prostaglandin F2α hormone on the estrus response and pregnancy in Ongole crossbreed and Simental crossbreed cows reared using intensive and semi-intensive rearing systems. The data obtained will be analyzed using analysis of variance (ANOVA) and if there is a real effect, continue with further testing with Duncan's Multiple Range Test. The results of research on the percentage of estrus after the first and second injection of the prostaglandin hormone can be seen in the table. The highest percentage of estrus was in the S1P2 treatment with a percentage value of 80% and the lowest percentage value was in the S2P1 and S2P2 treatments with a percentage value of 40%. The percentage of estrus after the second injection, the percentage value for all treatments increased and the percentage of estrus was highest in the S1P2 treatment with a value of 100%. The average value of onset of estrus after the second injection of the PGF2α hormone was lower than the first injection. The longest duration of estrus in the treatment after the first PGF2α hormone injection was in the S1P2 treatment with an average of 24.75 hours, while the longest duration of estrus in the treatment after the second PGF2α hormone injection was in the S2P1 treatment with an average of 25 hours. PO cattle and Simental crossbreeds injected with PGF2α gave no different estrous responses. Intensive and semi-intensive rearing systems provide no different estrous responses. Raising PO cows using a semi-intensive rearing system injected with PGF2α provides an estrous response and high pregnancy rates (60), to be one of techniques to breed cattle of PO cow and have good impact to the success of a livestock business

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma

BackgroundPrimary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer).MethodsThis was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension.ResultsForty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events.ConclusionsLatanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life.Trial registrationThe study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

The Transcript Levels and the Serum Profile of Biomarkers Associated with Clinical Endometritis Susceptibility in Buffalo Cows.

Determining the gene expression and serum profile of the indicators linked to clinical endometritis susceptibility in Egyptian buffalo cows was the aim of this investigation. The buffalo cows that were enrolled were divided into two groups: forty infected buffalo cows with clinical endometritis and forty seemingly healthy buffalo cows that served as the control group. For the purposes of gene expression and biochemical analysis, ten milliliters of blood was obtained via jugular venipuncture from each buffalo cow. TLR4, IL-8, IL-17, NFKB, SLCA11A1, NCF4, Keap1, HMOX1, OXSR1, ST1P1, and SERP1 were manifestly expressed at much higher levels in the buffaloes with endometritis. On the other hand, the genes that encode SOD, CAT, NDUFS6, Nrf2, and PRDX2 were down-regulated. There was a significant (p < 0.05) elevation of the serum levels of non-esterified fatty acids (NEFAs), beta hydroxy butyric acid (BHBA), triglycerides (TGs), globulin, creatinine, and cortisol, along with a reduction in the serum levels of glucose, cholesterol, total protein albumin, urea, estrogen (E2), progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroxine (T4), prostaglandin F2 α (PGF2α), calcium, iron, and selenium, in the endometritis group in comparison with the control. However, no significant change was observed in the values of phosphorus, magnesium, copper, or zinc in either group. Within the selective breeding of naturally resistant animals, the variation in the genes under study and the changes in the serum profiles of the indicators under investigation may serve as a reference guide for reducing endometritis in Egyptian buffalo cows.

TREATMENT OF CLINICAL ANOESTRUS IN ARABIAN MARES BY A PROSTAGLANDIN F2 α|ή‎|‎ωϧΔΔ ‎‎|‎ ‎

A synthetic prostaglandin F2 α(PGF2 α) analogue, luprostiol* , was used in treatment of clinically anoestrus Arabian mares that suffered from abnormal persisting luteal function. Thirty two anoestrus mares were selected for this study after careful examination of their breeding history and a thorough genital examination which included rectal palpation of the genital tract and ovaries. The genital examination also included a vaginoscopy of the vagina and cervix. These mares were diagnosed as clinically anoestrus during the spring and summer months breeding season and received a single intramuscular injection of the prostaglandin F2 α. Twenty six mares (81%) responded to the treatment and came to oestrus within 2-4 days. Ovarian activity of the induced oestrus was monitored by rectal palpation and the mares were bred twice according to their follicular development. A total of 13 mares (54%) became pregnant as a result of the treatment and pregnancies were confirmed later by rectal palpation. This study reveals that the majority of non-cycling mares during the spring and summer months breeding season are in a prolonged luteal function rather than inactive ovaries or ‘true anoestrus. The study also demonstrates the efficiency of Iuprostiol in the treatment of clinically anoestrus mares.

Blood Sampling and Hormone Measurement for Determining the Stage in the Ovarian Cycle in Marmosets.

Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.

Untargeted Metabolomics of the Sea Cucumber, Bohadschia marmorata (Jaeger, 1833)

The marine invertebrates such as sea cucumber are regarded as sources of diverse bioactive compounds with promising health and nutritional benefits. Many commercially traded sea cucumber species have been explored, yet none of the local low-value types in the province of La Union, Philippines. This study aimed to establish a baseline metabolomic profile of Bohadschia marmorata (Jaeger, 1833). The identification of compounds in its body wall utilized an Orbitrap MS-based approach. Metabolites were annotated using Compound Discover 3.2, and similarity searches were performed from online databases. Eleven putatively identified compounds, which included saponin (3beta,5xi,9xi)-28-Hydroxy-28-oxoolean-12-en-3-yl-beta-Dgalac topyranosyl-(1-3)-[beta-D-glucopyranosyl-(1-2)]-beta-D-glucopyranosiduronic acid, fatty acids and their byproducts such as eicosanoid (11,12-Epoxy-(5Z,8Z,11Z)-icosatrienoic acid) and prostanoids (13,14-dihydro Prostaglandin F1?; 13,14-Dihydro-15-keto Prostaglandin A2), dicarboxylic acids (tetradecanedioic acid; dodecanedioic acid; suberic acid; NP-001596), and amino acid (4-Oxoproline). The metabolic profile of the B. marmorata body wall showed a diverse group of representative metabolites common among holothurians associated with innate defense mechanisms, structural composition, and products of metabolic pathways. There is, however, a need to further isolate these compounds using other methods and test their biological activities.

Early Embryonic Development in Agriculturally Important Species.

The fertilization of oocytes ovulated by pigs, sheep, cows, and horses is not considered a limiting factor in successful establishment of pregnancy. Pig, sheep, and cow embryos undergo cleavage to the blastocyst stage, hatch from the zona pellucida, and undergo central-type implantation. Hatched blastocysts of pigs, sheep, and cows transition from tubular to long filamentous forms to establish surface area for exchange of nutrients and gases with the uterus. The equine blastocyst, surrounded by external membranes, does not elongate but migrates throughout the uterine lumen before attaching to the uterine luminal epithelium (LE) to begin implantation. Pregnancy recognition signaling in pigs requires the trophectoderm to express interleukin 1 beta, estrogens, prostaglandin E2, and interferon gamma. Sheep and cow conceptus trophectoderm expresses interferon tau that induces interferon regulatory factor 2 that inhibits transcription of estrogen and oxytocin receptors by uterine epithelia. This prevents oxytocin-induced luteolytic pulses of prostaglandin F2-alpha from regressing the corpora lutea, as well as ensuring the secretion of progesterone required for maintenance of pregnancy. The pregnancy recognition signal produced by equine blastocysts is not known. Implantation in these species requires interactions between extracellular matrix (ECM) proteins and integrins as the conceptus undergoes apposition and firm attachment to the uterine LE. This review provides details with respect to early embryonic development and the transition from spherical to filamentous conceptuses in pigs, sheep, and cows, as well as pre-implantation development of equine blastocysts and implantation of the conceptuses.

The Effects of Saturated and Polyunsaturated Fatty Acids on Reproductive Performance and Reproductive Hormonal Changes in Dairy Cows at the Transition Period

Reproductive success is crucial in dairy farming as it heavily relies on the consumption of a complete mixed ration for the diet. The current study investigated the effects of adding saturated (SFA) and polyunsaturated fatty acids (PUFAs) to dairy cows' diets on reproductive performance and reproductive hormones during the transition period. A total of 30 Holstein dairy cows were randomly divided into three groups (10 animals in each group), based on parity and body condition score. The cows had an initial body weight of 567.5 ± 40.3 kg (mean ± SD), a body condition score of 3.5 ± 0.26 out of 5 (mean ± SD), and a parity of 1.7 ± 0.02 (mean ± SD). The control group received a balanced ration meeting all the nutrient requirements according to the National Research Council (NRC) guidelines. The SFA group received 1.4% of dry matter (DM) as palm oil (RumiFat®), while the omega group had 5% of DM as safflower (a source of n-6 fatty acids) added from 21 days before parturition to 21 days after, and 4% of DM as flaxseed (a source of n-3 fatty acids) added from 21 to 42 days after parturition. In the Omega group, estradiol concentration significantly increased on artificial insemination (AI) day (12.54 pg/mL). Additionally, serum prostaglandin F2-alpha concentration was significantly higher in the omega group (0.732 pg/mL on day 7 and 1.68 pg/mL on day 14) compared to other groups. The control group exhibited the highest progesterone concentrations at 14 and 21 days post-calving compared to the other groups, other groups. whereas the omega group highest concentration five days after AI. The omega group also showed a significantly higher mean number of follicles &gt;10mm and larger ovulatory follicle diameter. Moreover, a higher percentage of pregnant cows at 120 days in milk, fewer open days, and lower service per conception were observed in the omega group compared to the other groups. In conclusion, supplementing dairy cows' diets with PUFAs during the transition period positively influenced ovarian function, hormone levels, and reproductive performance.

Prostaglandin F2 Receptor Negative Regulator (PTGFRN) Expression Correlates With a Metastatic-like Phenotype in Epidermoid Carcinoma, Pediatric Medulloblastoma, and Mesothelioma.

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein associated with metastatic characteristics of certain cancer types. However, it remains poorly characterized and its direct function in cancer remains unclear. The study presented here aims to further examine whether PTGFRN expression affects a cancer cell's phenotype, as well as metastatic-like characteristics. We used stable shRNA and cDNA transfections to respectively knockdown and overexpress PTGFRN in three different cancer cell lines, two of which are representative of rare and aggressive cancers (Mesothelioma and Pediatric Medulloblastoma). We then examined the characteristics of the resulting clones and showed a decrease in proliferation, migration, colony formation, and spheroid growth capabilities in cells where PTGFRN expression had been inhibited, while cells overexpressing PTGFRN showed the opposite. In addition, we showed that PTGFRN displayed direct binding to two protein partners, Integrin β1 and E. Cadherin, the latter of which is a novel direct binding partner to PTGFRN. Furthermore, silencing PTGFRN expression impacted the cellular process of autophagy, thereby providing another avenue by which PTGFRN potentially contributes to a cancer cell phenotype. Our findings demonstrate the potential role of PTGFRN in cancer metastasis and suggest PTGFRN as a future target for drug development in the treatment of metastatic cancers.

Influence of early progesterone removal on follicular development, expression of estrus, and pregnancy rates in presynchronized postpartum beef cows

The objective of this study was to evaluate the impact of early progesterone removal on pregnancy rates to fixed-time artificial insemination (FTAI) in presynchronized beef cows. Postpartum beef cows (n = 882) were randomly assigned to 1 of 2 treatments: 1) 7&7 Synch: cows received a controlled internal drug release insert (CIDR) and a 25-mg injection of prostaglandin F2α on day 0, 100 μg of GnRH on day 7, a second injection of prostaglandin F2α (PG2) at CIDR removal on day 14, and a second injection of GnRH at FTAI 60–66 h after PG2 (day 17); 2) 7&6 Synch: cows received the same treatment as 7&7 Synch; however, CIDR removal occurred in conjunction with PG2 on day 13, while FTAI remained at 60–66 h after CIDR removal (day 16). Ovarian ultrasonography was performed to determine follicle diameter at PG2 and FTAI in a subset of cows (n = 40). Cows exposed to the 7&7 Synch tended to have larger follicle diameter at PG2 compared with 7&6 Synch cows (P = 0.09); however, there were no differences in follicle diameter at FTAI. No differences were determined between treatments for the expression of estrus (7&7 Synch: 61.6 ± 5.30; 7&6 Synch: 54.1 ± 5.45; P = 0.31) or pregnancy rates to FTAI (7&7 Synch: 60.8 ± 3.83; 7&6 Synch: 57.0 ± 3.84; P = 0.42). In conclusion, early removal of progesterone did not impact pregnancy rates in presynchronized beef cows.

Effects of yellow mealworm (Tenebrio molitor) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome in broiler chickens

The goal of this study was to evaluate the effects of Tenebrio molitor (TM) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome of broiler chickens. A total of 600 1-d-old male Liangfenghua broilers were randomly assigned to five equal groups with 5 replicates and 24 birds in each replicate. The dietary treatments were as follows: the control group (TM0 group) was fed a basal diet, and the experimental groups were fed experimental diets in which 3% (TM3 group), 5% (TM5 group), 7% (TM7 group) and 9% (TM9 group) TM larvae meal included in the basal diet, respectively. The feeding period was 70 d. The results showed that body weight (BW) and average daily gain (ADG) significantly increased (p < 0.05) in response to dietary 3% TM larvae meal supplementation at the age of 70 d. Serum concentrations of triglyceride (TG) and serum activity of aspartate aminotransferase (AST) decreased (p < 0.05) in 3% TM larvae meal-fed broilers. UHPLC-MS/MS-based metabolomics analysis revealed that a total of 55 significantly different metabolites were obtained in the caecal contents of dietary TM larvae meal supplemented broilers. The relative contents of 28 metabolites such as trans-4-hydroxy-L-proline, thymine and retinoic acid were significantly up-regulated (FC > 1.5) and the relative contents of 27 metabolites like prostaglandin F2α, glucocorticoids and prostaglandin E2 were significantly down-regulated (FC < 0.667) in the TM3 group. The main altered pathways were clustered into arachidonic acid metabolism, primary bile acid metabolism and propionic acid metabolism. In conclusion, the results indicated that supplementation of 3% TM larvae meal can improve growth performance, reduce the activity of serum AST and the content of TG, and regulation of the pathways of lipid, amino acid, and sugar metabolism in the caecum of broilers by improving nutrient digestion and absorption.

The effectiveness of different hormone protocols for improving ovarian function before ovum pick-up in crossbred Japanese black cattle.

Producing and transferring embryos in vitro are profitable for enhancing premium beef genetics. Reducing costs and enhancing the effectiveness of hormone protocols before ovum pick-up (OPU) yield advantages. This study aimed to confirm that estradiol benzoate (EB) treatment resulted in more medium- and large-sized follicles before OPU and of higher oocyte quality after OPU than non-hormonal treatments, comparable to those undergoing gonadotropin-releasing hormone (GnRH) with follicle-stimulating hormone (FSH) plus prostaglandin F2α (PGF2α) and progesterone-releasing controlled internal drug release (CIDR) or EB with progesterone-releasing CIDR hormonal treatments. 30 crossbred Japanese black cows were divided into five equal groups, which were either untreated or treated with different hormone protocols before OPU. Group 1 (cows in estrus) and group 2 (cows in diestrus) were the untreated controls. Cows in group 3 were treated with GnRH + FSH + CIDR + PGF2α. Cows in group 4 received EB, and those in group 5 received EB + CIDR + PGF2α. After administering the protocols, all cow follicles were examined through ultrasonography and categorized by size. Subsequently, all cows underwent OPU, and the oocytes were collected and graded from A to D according to standard criteria. Group 3 presented the highest large follicle numbers, and groups 3-5 had more medium follicle numbers, not different among groups but they had this parameter more than those of control groups 1 and 2. Moreover, groups 3-5 did not differ in combined grades A + B oocytes (good-quality oocytes). Groups 3 and 4 had more A + B oocytes than control groups 1 and 2, whereas group 5 was not different in this parameter from group 1. Among the three hormone protocols, EB treatment proved the most cost-effective and efficient, yielding more high-quality oocytes compared to the non-treatment protocols. To reduce the limitations of EB use in the future, this study suggests researching natural EB phytoestrogens as alternative treatments for improving ovarian function before OPU in other cattle breeds.

Bovine somatotropin increases the pregnancy rate in fixed-time artificial insemination in beef cattle.

This study evaluated the effect of bovine somatotropin (bST) on pregnancy rate (PR) and size of the dominant follicle (DF) on the day of intravaginal progesterone (P4) removal in protocols for fixed-time artificial insemination (FTAI). Bos indicus (Nellore) females (n = 392) were distributed into three groups. The control group (CG; n = 92) received an intravaginal P4 device + estradiol benzoate on day (d)0; prostaglandin F2α on d7 (first application); removal of P4 + estradiol cypionate (EC) + PGF2α (second application) + ultrasound (US) of the DF on d9; the FTAI was performed on d11; and pregnancy diagnosis (PD) was performed on d45. The bST group (bSTG; n = 142) underwent the same protocol as the CG, except that the animals received 125 mg of bST on d7. The equine chorionic gonadotropin (eCG) group (eCGG; n = 158) underwent the same protocol as the CG, except that the animals received 300 IU of eCG on d9. The PRs of the bSTG, eCGG, and CG were 48%, 48%, and 35%, respectively (p < .05); the bSTG and eCGG showed greater PRs, with follicles 6-7.9 mm (p < .05) and 8-8.9 mm in diameter, respectively. The bSTG exhibited a greater dimension of the DF on d9 of the protocol (p < .05). The eCGG had higher PRs with a body condition score (BCS) of 2.5, and the bSTG had a BCS of 3.0 (p < .05). It was concluded that bST increased PR, bST showed better performance in smaller DF and larger follicular diameter on d9 of the protocol, eCG acted better on animals with lower BCSs, and bST can be used in FTAI.

BCG vaccination is associated with longitudinal changes in systemic eicosanoid levels in elderly individuals: A secondary outcome analysis

We investigated how BCG vaccination affects the levels of certain eicosanoids, namely Leukotriene B4, 15-epimer of LXA4, prostaglandin F2, Lipoxin A4, Prostaglandin E2 and Resolvin D1 in the plasma of healthy elderly individuals (aged 60–80) before vaccination, one month post-vaccination (M1), and six months post-vaccination (M6). This study is part of the clinical trial "BCG Vaccine Study: Reducing COVID-19 Impact on the Elderly in Indian Hotspots," registered in the clinical trial registry (NCT04475302). While some primary outcomes have been previously reported, this analysis delves into the immunological outcomes. Our findings indicate that BCG vaccination leads to reduced plasma levels of 15-epi-LXA4, LXA4, PGE2, and Resolvin D1 at both M1 and M6. In contrast, there is a notable increase in circulating levels of LTB4 at these time points following BCG vaccination. This underscores the immunomodulatory effects of BCG vaccination and hints at its potential to modulate immune responses by dampening inflammatory reactions.

Decidual Cells Block Inflammation-Mediated Inhibition of 15-Hydroxyprostaglandin Dehydrogenase in Trophoblasts

Chorioamnionitis generates prostaglandin (PG) E2 and F2α, promoting fetal membrane rupture, cervical ripening, and uterine contractions. 15-Hydroxyprostaglandin dehydrogenase (HPGD) contributes to pregnancy maintenance by inactivating PGs. Herein, the role of decidual cells in the regulation of HPGD expression at the maternal-fetal interface was investigated. HPGD immunostaining was primarily detected in anchoring villi and choriodecidual extravillous trophoblasts (EVTs) during pregnancy. Chorionic EVTs adjacent to the decidua parietalis exhibited significantly higher HPGD levels than those adjacent to the amnion. HPGD histologic score levels were significantly lower in choriodecidua from chorioamnionitis versus gestational age-matched controls (means±SEM, 132.6±3.8 versus 31.2±7.9; P<0.05). Conditioned media supernatant (CMS) from invitro decidualized term decidual cells (TDCs) up-regulated HPGD levels in differentiated EVTs, primary trophoblasts, and HTR8/SVneo cells. However, CMS from 5 μg/mL lipopolysaccharide or 10ng/mL IL-1β pretreated TDC cultures down-regulated HPGD levels in HTR8/SVneo cultures. Similarly, direct treatment of HTR8/SVneo with lipopolysaccharide or IL-1β significantly reduced HPGD levels versus control (P<0.05) but not in TDC-CMS pretreated HTR8/SVneo cultures. Collectively, these results uncover a novel decidual cell-mediated paracrine mechanism that stimulates levels of trophoblastic HPGD, whose function is to inactivate labor-inducing PGs, thereby promoting uterine quiescence during pregnancy. However, infectious/inflammatory stimuli in decidual cells cause a paracrine inhibition of trophoblastic HPGD expression, increasing PGE2/PGF2α levels, thereby contributing to preterm birth.

Unraveling the role of lipid droplets and perilipin 2 in bovine luteal cells.

Steroidogenic tissues contain cytosolic lipid droplets that are important for steroidogenesis. Perilipin 2 (PLIN2), a structural coat protein located on the surface of lipid droplets in mammalian cells, plays a crucial role in regulating lipid droplet formation and contributing to various cellular processes such as lipid storage and energy homeostasis. Herein, we examine the role that PLIN2 plays in regulating progesterone synthesis in the bovine corpus luteum. Utilizing gene array databases and Western blotting, we have delineated the expression pattern of PLIN2 throughout the follicular to luteal transition. Our findings reveal the presence of PLIN2 in both ovarian follicular and steroidogenic luteal cells, demonstrating an increase in its levels as follicular cells transition into the luteal phase. Moreover, the depletion of PLIN2 via siRNA enhanced progesterone production in small luteal cells, whereas adenovirus-mediated overexpression of both PLIN2 and Perilipin 3 (PLIN3) induced an increase in cytosolic lipid droplet accumulation and decreased hormone-induced progesterone synthesis in these cells. Lastly, invivo administration of the luteolytic hormone prostaglandin F2α resulted in an upregulation of PLIN2 mRNA and protein expression, accompanied by a decline in serum progesterone. Our findings highlight the pivotal role of PLIN2 in regulating progesterone synthesis in the bovine corpus luteum, as supported by its dynamic expression pattern during the follicular to luteal transition and its responsiveness to luteotropic and luteolytic hormones. We suggest PLIN2 as a potential therapeutic target for modulating luteal function.

The regulation of the expression of prokineticin 1 and its receptors and its mechanism of action in the porcine corpus luteum

Prokineticin 1 (PROK1) is an important factor in pregnancy establishment in pigs, acting at the embryo–maternal interface and the corpus luteum (CL). Estradiol-17β (E2) is the primary pregnancy recognition signal in pigs, and its effects are augmented by luteotropic prostaglandin E2 (PGE2). On the contrary, prostaglandin F2α (PGF2α) exerts mainly a luteolytic effect. The present study aimed to elucidate whether E2, PGE2, and PGF2α regulate the expression of PROK1 and its receptors in the porcine CL and to determine the PROK1 effect on luteal endothelial cells and pathways that may be involved in this regulation. The effects of E2, PGE2, and PGF2α on the expressions of PROK1 and its receptors in the CL were studied using an in vitro model of ultrathin luteal tissue explants model. Additionally, the effects of E2 and PGE2 on the PROK1 system were determined using an in vivo approach, in which the hormones were administered into the uterine lumen to imitate their secretion by embryos. Endothelial cell proliferation was measured using the colorimetric method. E2 acting via estrogen receptors simulated the mRNA and protein expressions of PROK1 and PROKR1 in CL explants in vitro (p < 0.05). The simultaneous action of E2 with PGE2 enhanced the expression of luteal PROK1 mRNA in vitro (p < 0.05). Estradiol-17β acting alone significantly increased PROK1 mRNA levels in vivo, whereas E2 simultaneously administered with PGE2 significantly elevated the PROK1 mRNA expression and PROKR1 mRNA and protein contents in CLs adjacent to uterine horns receiving hormonal infusion compared with CLs adjacent to placebo-treated uterine horns (p < 0.01). The PROK1 protein expression was significantly higher in the CLs of pigs treated with E2, PGE2, and E2 together with PGE2 than in the control group. PGF2α increased the PROK1 mRNA content in CLs on days 12 and 14 of the estrous cycle (p < 0.05). The expression of PROKR2 at the mRNA and protein levels remained unchanged in response to in vitro and in vivo treatments. PROK1 stimulated the proliferation of luteal endothelial cells by activating the MAPK, AKT, and mTOR pathways (p < 0.05). In summary, the luteal expressions of PROK1 and PROKR1 in early pregnancy are regulated by E2 and PGE2. PROK1 stimulates luteal angiogenesis by activating the MAPK, AKT, and mTOR pathways. The regulation of luteal PROK1 expression by PGF2α indicates PROK1's putative role during luteolysis. We conclude that PROK1-PROKR1 signaling supports luteal function during CL rescue in pregnancy in pigs.