PGF2 Research Articles

179 Cost and Profit Per Pregnancy Associated with Estrous Synchronization Utilizing Estrus Detection And/Or Fixed-Time Artificial Insemination

Abstract This experiment aimed to compare synchronization cost associated with two protocols: one utilizing estrus detection (6d; PG 6-d CIDR+TAI) and one utilizing strictly fixed-time artificial insemination (FTAI; 7d; 7-d CO-Synch+CIDR). Cows and heifers (n = 657) from 10 herds in three states were grouped by days postpartum and age, and randomly assigned to one of two protocols. Cows and heifers assigned to the 6 d protocol were administered prostaglandin F2α (PGF) on d-9, CIDR insertion and administration of gonadotropin-releasing hormone (GnRH1) on d -6, and CIDR removal and PGF administration on d 0. Cows and heifers that were assigned to the 6-d protocol were subsequently grouped into three treatments based on presence and/or timing of estrus and insemination (PG1: Insemination before CIDR insertion, n = 136; PG2: Insemination after CIDR removal, n = 26; T6: Insemination at TAI, n = 166). Cows and heifers assigned to the 7-d protocol (T7: Insemination at FTAI, n = 329) were administered GnRH1 and CIDR insertion on d -7, followed by CIDR removal and PGF administration on d 0. For all animals, FTAI and GnRH2 administration occurred at 54 h (heifers) or 66 h (cows) after CIDR removal. Pregnancy was determined from d 30 to d 40 after FTAI by transrectal ultrasonography. Total cost and profit per pregnancy was calculated for herds of 30, 100, 300, and 500 females with varying estrus response and pregnancy rates. Expenditures were calculated assuming synchronization costs (PG1 = $46.15, PG2 = $75.05, T6 = $77.91, T7 = $73.72), general labor cost considering herd size and handling days, as well as estrus detection labor cost assuming $10.00 per h, a 95% overall herd pregnancy rate, a 1:40 bull:cow ratio, and average bull purchase price of $3,000.00. Revenue was estimated assuming a maximum 205-d weaning age, 1.09 kg/d gain, $200.00/45.4 kg, and 85% weaning rate. Differences in estrus response and pregnancy rate were determined using the GLIMMIX procedure of SAS (v9.4), including herd as a random variable. Estrus response was greater (P < 0.0001) in females assigned to the 6d (73 ± 4%) compared with the 7d (53 ± 4%) protocol; however, pregnancy success was similar among treatment groups (P = 0.32; PG1 = 45 ± 4%, PG2 = 58 ± 10%, T6 = 46±4%, T7 = 52±3%). At the observed estrus response and pregnancy rate for each treatment group, the 6d protocol resulted in a decreased cost per pregnancy compared with the 7d protocol [Table 1; herds of: 30 = ($3.53), 100 = ($5.16), 300 = ($6.58), 500 = ($7.00) females]. Additionally, using the same variables, the 6d protocol resulted in an increased profit per pregnancy compared with the 7d protocol (herds of: 30 = $3.50, 100 = $6.41, 300 = $17.27, 500 = $12.06 females). These results suggest that labor associated with estrus detection may be offset by the proportion of calves subsequently born earlier within the calving season, allowing for improvements to profitability, especially in larger herds.

PSIII-7 Effect of Time of Estrus on Conception Rate for a Sexed Semen Artificial Insemination Protocol in Multiparous Beef Cows

Abstract Sexed semen artificial insemination is a breeding technique that allows producers to shorten breeding seasons, optimize genetics through use of superior semen, create calves based on sex preference, and increase profitability. Sexed semen is a technology that sorts semen by differences in DNA content between X (female) and Y (male) bearing sperm. However, sexed semen practices have yet to be widely used in beef cows due to reduced sperm numbers, low conception rates, and increased costs. The objective of this study was to determine the effect of time of estrus upon fixed-time artificial insemination (FTAI) of sex-sorted semen on conception rate using two different estrous synchronization protocols. Multiparous commercial beef cows (n = 73) were randomized by age, body condition score (BCS), and days post-partum at the University of Arkansas Livestock and Forestry Research Station in Batesville. Both synchronization treatments (TRT) used a controlled internal drug releasing device (Eazi-breed CIDR; 1.38g progesterone) inserted intravaginally on d -14 of the protocol simultaneous to administration of prostaglandin F2α (PGF; 500µg cloprostenol sodium; Estrumate). In the first treatment (TRT 1; 7&7 Synch), gonadotropin-releasing hormone (GnRH; 86µg gonadorelin; Fertagyl) was administered on d -7. In the second treatment (TRT 2; 8&6 Synch), GnRH was administered on d -6. Both treatments were then administered PGF simultaneous to CIDR removal on d 0, 66 ± 2h before FTAI and administration of GnRH. Standing heat (estrus) was visually detected every 3 h for 30 min intervals between CIDR removal and FTAI. Heat detection patches were used in conjunction with visual detection of estrus. Time of estrus was signified as time of standing immobile when mounted in combination with presenting a patch score of 4 (>75% color removed). Time of estrus (TD) was deviated from time of FTAI and categorized into three equal time groups (Grp 1 = 0 to 11.0 h; Grp 2 = 11.01 to 22.0 h; and Grp 3 = 22.01 to 33.0 h). Conception rate (CR) was determined via ultrasound 37 ± 2 d after FTAI. Data were analyzed using the GLIMMIX procedure of SAS 9.4. CR did not differ by age of dam (P = 0.58), BCS (P = 0.48), or TRT (P = 0.83). However, TD had an effect on CR (P = 0.002); and resulted in CR of 45% (Grp 1), 87% (Grp 2), and 42% (Grp 3). In conclusion, these results indicate artificially inseminating cows with sexed semen between 11.01 and 22.0 h after time of standing estrus will increase pregnancy rates for multiparous commercial beef cattle.

292 Tandem Administration of Prostaglandin F2α and Gonadotropin-Releasing Hormone in Beef Heifers and Cows as a Convergent Presynchronization Method in the 7 & 7 Synch Protocol

Abstract An experiment was designed to evaluate modifications to the 7 & 7 synch protocol with the hypothesis that tandem administration of prostaglandin F2α (PG) and gonadotropin-releasing hormone (GnRH) during the presynchronization portion of the protocol would generate a convergent ovarian response among anestrous and estrous cycling females. Nulliparous (n = 153), primiparous (n = 92), and multiparous (n = 413) Angus-cross females across four locations were blocked based on parity and pre-treatment cyclicity status (presence or absence of a corpus luteum) as assessed via transrectal ovarian ultrasonography. Within block, females were randomly assigned to one of three treatments. Females assigned to the 7 & 7 Synch treatment received an intravaginal progesterone-releasing insert (CIDR) and administration of PG on day 0, administration of GnRH on day 7, and administration of PG coincident with CIDR removal on day 14. Females assigned to 7 & 7 Synch + G received the same treatment schedule with the modification that GnRH was administered in tandem with the PG on day 0. Females assigned to 7 & 7 Synch + G + P received GnRH in tandem with PG on both day 0 and day 7 of the treatment schedule. Fixed-time artificial insemination (FTAI) was performed at 54 h after CIDR removal for nulliparous females and at 66 h for primiparous and multiparous females. Transrectal ovarian ultrasonography was performed on day 7 and day 14 to characterize the largest follicle diameter (LFD) as well as the presence/absence and number of corpora lutea (CL). Expression of estrus before FTAI was characterized in three locations using estrus detection patches (Estrotect. Approximately 75 to 90 days after FTAI, pregnancy status was determined via transrectal ultrasonography. Day 7 CL status was affected by treatment (P = 0.002), with a greater proportion of females presenting with CL on Day 7 when treated with the modified treatments (64%) as compared with the 7 & 7 Synch treatment (31%). Day 14 LFD was affected by treatment (P = 0.002), with a larger average LFD among females treated with 7 & 7 Synch + G + P (12.0 mm) as compared with 7 & 7 Synch (11.4 mm) or 7 & 7 + G (10.7 mm). Pregnancy rate to FTAI was affected by pre-treatment cyclicity status (P < 0.0001) and semen type (P = 0.0003) and tended to be affected by treatment (P = 0.09) with 7 & 7 Synch + G + P tending to result in a greater proportion pregnant (58.86%) as compared with 7 & 7 Synch (49.17%) and 7 & 7 Synch + G (48.79%). Tandem administration of GnRH and PG on days 0 and 7 of the 7 & 7 Synch protocol effectively generated a convergent ovarian response among anestrous and estrous cycling beef females and tended to result in increased pregnancy rates to FTAI.

291 Impact of Early Resynchronization in Combination with Color Doppler Ultrasonography on Cumulative Pregnancy Rates in Postpartum Beef Cows

Abstract The objective of this study is to evaluate a GnRH and progesterone-based early resynchronization strategy combined with color Doppler ultrasonography for early pregnancy diagnosis. Postpartum Bos taurus beef cows (n = 375) from four locations were enrolled in a completely randomized design, where cows were randomly assigned to 1 of the 2 treatments: 1) Natural Service (NS), cows were exposed to a 7-d CO-Synch + CIDR protocol followed by fixed-time artificial insemination (day 0). On day 15, cows were exposed to natural service for the remainder of the study; or 2) Early Resynchronization (ER), cows were exposed to a 7-d CO-Synch + CIDR protocol followed by fixed-time artificial insemination (day 0). On day 15, a controlled internal drug release (CIDR) device was inserted. On day 20, CIDR was removed, and pregnancy was estimated based on luteal blood perfusion using color Doppler ultrasonography. Non-pregnant cows received a 25-mg injection of prostaglandin F2α at CIDR removal and were fixed-timed-AI concurrently with a 100-μg injection of GnRH 60 to 66 h later. Pregnancy diagnosis and fetal aging were performed on day 53 using conventional ultrasonography. Pregnancy rate to the first AI was greater (P = 0.03) for NS compared with ER (70.25% vs 59.29%, respectively). Pregnancy rates for the second service were also greater (P = 0.01) for NS compared with ER (65.67 vs 42.93%, respectively). Cumulative pregnancy rates to AI did not differ between treatments (P = 0.38); however, cumulative pregnancy rates (first and second service) were greater (P < 0.01) for NS compared with ER (90 vs 77.73%, respectively). In conclusion, the proposed early resynchronization strategy using color Doppler ultrasonography resulted in fewer pregnancies compared with natural service as the second service strategy. Moreover, the proposed ER decreased pregnancy rates to the first insemination, indicating a detrimental effect of ER on pregnancy establishment.

PSII-12 Influence of Dietary Methionine and Guanidinoacetic Acid on Estrous Cycles and Early Pregnancy in Beef Heifers

Abstract Interest is growing in methods to apply precision nutritional supplements strategically during the peri-conceptual period to enhance progeny performance of beef females. Studies where supplemental methionine (MET) was provided to bovine females in the peri-conceptual period demonstrated epigenetic modifications in muscle of the progeny. Guanidinoacetic acid (GAA) has been fed directly to livestock to increase creatine synthesis, but has not been evaluated for use in fetal programming. We fed MET and GAA to cross-bred heifers during the peri-conceptual period as a 2 x 2 factorial design to influence carcass characteristics of their steer calves. It was, therefore, important to determine if the interactions of dietary MET and GAA in the peri-conceptual period would alter reproductive efficiency. The null hypothesis was that these supplements would not alter reproductive efficiency of beef heifers when fed in the peri-conceptual period. Heifers were divided into four breeding groups for management purposes. On day -63, heifers (n = 20/diet, age = 384.1 ± 1.1 d) were assigned HeatTime collars and individually fed MET (10 g/d), GAA (40 g/d), the combination (MET + GAA), or ground corn carrier (CON) for 126 days. On day -9, heifers received 100 mg of gonadotropin releasing hormone and a CIDR. On day -2, the CIDR was removed and luteolysis was initiated with 25 mg of prostaglandin F2a. All heifers were inseminated with male sexed semen from a single sire and administered a second 100 mg injection of gonadotropin releasing hormone on day 0. On day 63, a blood sample was collected from all pregnant heifers (CON n = 10; MET n = 8; GAA n = 7; MET + GAA n =10) to evaluate circulating progesterone concentrations. Reproductive tracts were collected to determine CL weight, gravid uterine weight, and placentome number. Data were analyzed using the MIXED procedure of SAS with group, MET, GAA, and the interaction of MET and GAA as fixed effects. Days to first estrus were greater and number of estrus events prior to synchronization were fewer in CON heifers compared with supplemented heifers (P < 0.05). Luteal weight tended to be greater in heifers supplemented with MET compared with CON and GAA heifers (P = 0.09), but peak intensity of estrus, concentration of progesterone at day 63 of pregnancy, gravid uterine weight, and placentome number did not differ due to diet (P > 0.10). Supplementation with MET or GAA may improve onset of puberty but does not negatively alter reproductive performance in cross-bred beef heifers. These supplements can be used for fetal programming of muscle development in steer progeny without negatively impacting reproductive performance in the breeding herd. USDA is an equal opportunity provider and employer. Funded in part by USDA-NIFA-AFRI # 2022-67015-36196.

Comparative evaluation of estrus synchronization protocols on reproductive performance and estrus behavior in Barbados Black Belly sheep.

Estrus synchronization of ewes has been accomplished using several protocols with various degrees of success in improving reproductive efficiency and obtaining the most effective protocol used in sheep farming. This study aimed to compare the effectiveness of three treatment protocols and to record the intensity and duration of estrus signs and pregnancy rate in Barbados Black Belly (BBB) sheep. Thirty-two primipara BBB ewes aged 18-24 months were equally divided into three treatment groups. T1: the ewes were injected intramuscularly with 2 mL Lutalyse (PGF2α) (10 mg) on days 0 and 10. T2: 1 mL Fertiline (50 μg; Gonadorelin acetate) on day 0 and 2 mL lutalyse (10 mg) on day 7. T3: 1 mL fertiline (50 μg) on day 0, 2 mL lutalyse (10 mg) on day 7, and 1 mL Fertiline (50 μg) on day 9. Estrus response was assessed using naturally mating rams and ewes. Pregnancy was determined using ultrasonography between 55 and 80 days after the last hormonal injection. The following estrus signs were noted: Swollen vulva, mucus discharge, sniffing, excitement, loss of appetite, mounting, and rapid tail movement. Of the expressed signs, swollen vulva was most frequent, whereas loss of appetite and mucus discharge were the least overt signs recorded. The estrus response (%), onset (%), and duration (h) in ewe synchronization of the three treatment protocols were 100%, 58.3 ± 23.4%, and 48.0 ± 18.2 h (T1), 100%, 61.7 ± 41.2%, and 45.0 ± 27.0 h (T2), and 37.5%, 32.1 ± 1.7%, and 29.2 ± 1.25 h (T3), respectively. The pregnancy rates were 87.5%, 87.5%, 37.5%, and 50.0% in T1, T2, T3, and T4, respectively. Prostaglandin F2α+PGF2α and GnRH+PGF2α synchronization protocols were more effective in the fertilization of BBB ewes with better expression of estrus signs compared with the GnRH+PGF2α+GnRH (OVS) protocol.

Comparative pregnancy diagnosis of digital rectal palpation technique, ultrasonography, progesterone assay and non-return-to-heat in Red Sokoto goat.

Comparative pregnancy diagnosis was carried out to evaluation the effectiveness of digital rectal palpation technique in Red Sokoto goat, at Small Ruminant Research Program of National Animal Production Research Institute, Shika, Zaria. Forty two does were randomly divided into groups A, B and C, (n = 14 each). Semen was collected from two Red Sokoto bucks using artificial vagina, processed and stored at 4˚C. Oestrus was synchronised with prostaglandin F2-alpha, and oestrus detected by apronised bucks and visual observation. Breeding was by artificial inseminating for groups A and B while group C bred by natural service. Comparative pregnancy diagnosis was carried out using ultrasonography (US) and digital rectal palpation technique (DRP) on day 14, 21, 28 and 126, while progesterone assay (P4) and non-return-to-heat (NRH) on day 21, post-breeding. Pregnancy rates on day 21 were 64.3 %, 92.9 % and 100 % (US); 42.9 %, 57.1 % and 57.1 % (DRP); 78.6 %, 78.6 % and 100 % (P4); 85.7 %, 78.6 % and 92.9 % (NRH). There was significant (P < 0.05) difference between US, DRP, P4 and NRH in groups B and C. It was concluded that DRP technique was effective in early pregnancy diagnosis (days 14, 21, and 28) in Red Sokoto goat does.

Hepatotoxicity effects of Ageratina adenophora, as indicated by network toxicology combined with metabolomics and transcriptomics

Ageratina adenophora (A. adenophora), one of the prominent invasive plants in the Asian continent has shown toxicity in animals. However, studies examining the gene expression and metabolic profiles of animals that ingest A. adenophora have not yet been reported in the literature. Therefore, considering the wide distribution of A. adenophora, it is necessary to elucidate the toxic mechanisms of A. adenophora via multiomics approach. In this study, we identified and evaluated the toxic mechanisms of action associated with bioactive compounds in A. adenophora by using network toxicology studies combined with metabolomics and transcriptomics and found that 2-deoxo-2-(acetyloxy)− 9-oxoageraphorone, 10Hβ-9-oxo-agerophorone, 10Hα-9-oxo-agerophorone, nerolidol, 9-oxo-10,11-dehydro-agerophorone were the main active toxic compounds in A. adenophora. In addition, using metabolomics approach we identified differential metabolites such as L-pyroglutamic acid, 1-methylhistidine, prostaglandin F2alpha and hydrocortisone from A. adenophora and these metabolites were involved in amino acid metabolism, lipid metabolism and signal conducting media regulation. Based on network toxicological analysis, we observed that, A. adenophora can affect the Ras signaling, Phospholipase D signaling and MAPK signaling pathways by regulating EGFR, PDGFRB, KIT and other targets. From the results of this study we concluded that A. adenophora induces liver inflammatory damage by activating the EGFR expression and Ras/Raf/MEK/ERK signaling pathways as well as affect nutrients metabolism and neuron conduction.

Differences in Prostaglandin f2α Level in Adolescent Girls Experienced and Not Experienced Premenstrual Syndrome: A Cross-Sectional Study

This study aims to determine the differences in Prostaglandin f2α concentration in female adolescents who experienced and did not experience Pre-Menstrual Syndrome (PMS). Cross-sectional study conducted at a single institution. The sample for this study was female adolescents at the Darul Arqam Islamic Boarding School in Makassar, consisting of 50 adolescents who experienced PMS and those who did not experience PMS in a ratio of 1:1. Prostaglandin f2α levels were measured using an ELISA kit. The sample used was 5 cc blood from the median cubital vein by laboratory staff 5 days before menstruation. Data were analyzed descriptively and statistically. The results showed that the average Prostaglandin f2α in the group that experienced PMS (379.07) was higher compared to the group that did not experience PMS (101.23) with a p-value < 0.05, significantly. Furthermore, the group that experienced mild PMS had an average Prostaglandin f2α value of 283.32, while the group that experienced severe PMS had an average Prostaglandin f2α value of 454.31. The average Prostaglandin f2α level in the group who did not experience PMS, mild PMS, and severe PMS had a p-value < 0.05. This study concludes that there is a significant difference in the Prostaglandin f2α Level in adolescents who experience PMS and those who do not experience it and there are differences based on the severity of PMS.

Enhanced Microvascular Adaptation to Acute Physical Stress and Reduced Oxidative Stress in Male Athletes Who Consumed Chicken Eggs Enriched with n-3 Polyunsaturated Fatty Acids and Antioxidants-Randomized Clinical Trial.

This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session (ASTS) in competitive athletes. Thirty-one male athletes were assigned to a control (n = 17) or a Nutri4 group (n = 14) who consumed three regular or enriched chicken eggs per day, respectively, for 3 weeks. Significantly enhanced endothelium-dependent responses to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) were observed in the Nutri4 group but not in the control group after egg consumption. Formation of peroxynitrite and hydrogen peroxide in peripheral blood mononuclear cells, as well as serum concentration of 8-iso prostaglandin F2α, decreased in the Nutri4 group while remaining unchanged in controls. PORH and AChID were reduced post-ASTS compared with pre-ASTS, both before and after the diets, in both groups. However, the range of PORH responsiveness to ASTS (ΔPORH) increased after consumption of enriched eggs. These results suggest that consumption of enriched chicken eggs has a beneficial effect on microvascular endothelium-dependent vasodilation and the reduction of oxidative stress levels in competitive athletes. Also, microvascular adaptation to the ASTS was improved after consumption of Nutri4 eggs.

Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity

Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity.

Biotechnology of regulation of reproductive functions of Bos primigenius taurus

Since cattle are biologically capable of giving birth to only one calf per year, they are considered a single-fruited animal species. One of the cardinal methods of solving the problem of accelerated reproduction of livestock is biotechnological regulation of reproductive function in cows and synchronisation of their sexual activity. The aim of the study is to investigate the peculiarities of the reproductive function of Red Steppe cows under the influence of various methods of its regulation using modern hormonal agents. To evaluate the reproductive function of cows, generally accepted zootechnical methods were used, methods of variation statistics were used to calculate data, and biotechnological methods were used to regulate sexual activity in cows. Based on the analysis of the state of reproduction of the cattle herd, it was established that 164-187 cows and 85-96 heifers are artificially inseminated annually, which ensures the yield of calves per 100 cows of 89-91 heads and the annual introduction of 36 to 40 first-born calves per 100 cows. The shortened service period contributes to both a higher calf yield and an increase in milk yield, which is a desirable production effect. However, calving to conception interval, necessary to prepare the cow’s body for a new insemination, can be reduced to at least 30 days. Insemination of heifers with artificial insemination devices should be started when they reach a live weight of 314±6.5 kg, which will allow to obtain fertility from the first insemination at the level of 73.7-77.8% and thereby prevent obesity of heifers, which mainly reduces the percentage of fertility from the first insemination. It is necessary to establish obstetric and gynaecological examinations and treatment of problematic replacement heifers and cows, and it is advisable to use prostaglandin F2α analogues in combination with vitamins or biologically active drugs to stimulate the sexual function of cows and heifers. The use of prophylactic drugs will help to synchronise the heifers' sexual desire and increase their fertility during insemination. And the organisation of cattle reproduction and the proposed biotechnological ways to improve artificial insemination of the red steppe breed breeding stock will significantly improve their reproductive status, which will increase the overall economic efficiency of the industry

Targeted Mass Spectrometry Reveals Interferon-Dependent Eicosanoid and Fatty Acid Alterations in Chronic Myeloid Leukaemia.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, the detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of chronic myeloid leukaemia (CML), we found that the levels of intra- and extracellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), extracellular Prostaglandin F2α (PGF2α), extracellular 5-Hydroxyeicosatetraenoic acid (5-HETE), extracellular Palmitic acid (PA, C16:0) and extracellular Stearic acid (SA, C18:0), were altered in response to immunomodulation by type I interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism, with potential relevance in the context of cancer inflammation and CML.

Amelioration of Seminal Plasma Testosterone Concentration in Gembrong Goats after In Vivo Administration of PGF2α

The semen quality of Gembrong goats is lower than other goats and may be related to the low concentration of testosterone hormone. Implementation of reproductive technology using prostaglandin F2α (PGF2α) hormone is beneficial to increase the testosterone hormone in Gembrong goats. This study aimed to determine the effect of PGF2α injection on increasing testosterone levels in Gembrong goats. Male Gembrong goats (n=4), aged 2.5-4 years with similar body condition scores (BCS=3) were used in this study. Goats were divided into two treatment groups (n=2). Goats in group 1 (G1) were injected intramuscularly with 1 ml PGF2α (75 μg), while those in group 2 (G2) were injected with 1 ml physiological NaCl. Semen collection was carried out 30 minutes after treatment using an artificial vagina. Testosterone levels were measured using the enzyme-linked immunosorbent assay (ELISA). The collected data was tabulated and analyzed descriptively. The results showed that the average testosterone concentration of G1 was higher than G2 with respective concentrations of 6.41 ± 0.70 and 2.81 ± 1.75 ng/ml. It was concluded that administration of PGF2α in vivo could increase testosterone concentration in Gembrong goats.

Prostaglandin F2α synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F2α-dependent and F2α-independent mechanism.

Oxaliplatin (Oxa) is the first-line chemotherapy drug for colorectal cancer (CRC), and Oxa resistance is crucial for treatment failure. Prostaglandin F2α synthase (PGF2α) (PGFS), an enzyme that catalyzes the production of PGF2α, is involved in the proliferation and growth of a variety of tumors. However, the role of PGFS in Oxa resistance in CRC remains unclear. To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC. The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels. Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance (HCT116-OxR and HCT8-OxR) and their parental cell lines (HCT116 and HCT8) to assess its influence on cell proliferation, chemoresistance, apoptosis, and DNA damage. For determination of the underlying mechanisms, CRC cells were examined for platinum-DNA adducts and reactive oxygen species (ROS) levels in the presence of a PGFS inhibitor or its products. Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues. Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dose-dependent manner. Furthermore, overexpression of PGFS in parental CRC cells significantly attenuated Oxa-induced proliferative suppression, apoptosis, and DNA damage. In contrast, knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells (HCT116-OxR and HCT8-OxR) accentuated the effect of Oxa treatment in vitro and in vivo. The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa. Treatment with the PGFS-catalyzed product PGF2α reversed the effect of PGFS knockdown on Oxa sensitivity. Interestingly, PGFS inhibited the formation of platinum-DNA adducts in a PGF2α-independent manner. PGF2α exerts its protective effect against DNA damage by reducing ROS levels. PGFS promotes resistance to Oxa in CRC via both PGF2α-dependent and PGF2α-independent mechanisms.

Pharmacotherapy of glaucoma in terms of evidence-based medicine

Glaucoma is a disease associated with increased intraocular pressure (IOP). Of the pharmacological agents for treating glaucoma, there are drugs of the first (most effective and safe) and second-line treatment. First-line treatment includes prostaglandin analogs and beta-blockers. The currently used prostaglandin analogs (latanoprost, bimatoprost, tafluprost and travoprost) are PG F2α analogs that act through stimulation of FP receptors. They are distinguished by the optimal ratio of effectiveness and risk of side effects. They are convenient for the patient because for the therapeutic effect, it is enough to prescribe 1 time per day. As a result, it is rational to start the treatment of glaucoma with a drug in this group. In terms of pharmacoeconomics, the most affordable prostaglandin drug is latanoprost, which is generally as effective as other prostaglandin analogs. β-adrenergic blockers reduce the production of intraocular fluid, the formation of which is controlled by β1- and β2-adrenergic receptors. Therefore, non-selective β-blockers (timolol, levobunolol, metipranolol, and carteolol) have a pharmacodynamic advantage over selective β1-adrenergic antagonists (betaxolol). Conducted clinical studies of β-blockers have shown that given the cost, efficacy and safety, timolol was the most preferable treatment for glaucoma. In the presence of medical contraindications to the use of first-line drugs or to enhance their effectiveness, α2-agonists (apraclonidine and brimonidine), carbonic anhydrase inhibitors (usually local action: dorzolamide and brinzolamide), M-cholinomimetics (pilocarpine, carbachol and echothiopate), and also Rho-kinase inhibitors (ripasudil)

Ovarian Dynamics and Changes in Estradiol-17β and Progesterone Relationship with Standing Estrus, Preovulatory Follicles, and Ovulation Using Single Prostaglandin F2α Injection in Barbari Goats.

The purpose of the present research was to define ovarian follicular dynamics and plasma endocrine profiles in response to a single PGF2α injection, administered indiscriminately during the breeding season of Barbari goats. Ovarian dynamics were observed at every 12 h interval by using B mode ultrasonography, blood samples for hormonal analysis such as estradiol 17β and progesterone were collected at every 12 h interval, and bucks with aprons were used to identify standing estrus at every 6 h interval. Relative to PGF2α, the start of standing estrus and ovulation differ (p < 0.05) between early- (n = 7), intermediate- (n = 6), and late-responding (n = 6) goats. The highest plasma level of estradiol 17β was detected 12 h prior to ovulation. The average diameter of the ovulatory follicle and length of standing estrus were comparable (p > 0.05) between the goats. The corpus luteum degenerated more quickly (p < 0.05) in early- than intermediate- and late-responding goats. Dominant follicle diameter and estradiol 17β concentration also differ (p < 0.05) among groups. Although the plasma level of progesterone did not vary (p = 0.065), the variation in progesterone concentration with time differed (p < 0.05) amongst the goats. As a result, this research indirectly reveals that the beginning of standing estrus, end of estrus, and ovulation after PGF2α might fluctuate in Barbari goats because of follicular and hormonal dynamics during the luteal phase.

Reproductive performance in gilts submitted to non-steroidal therapies to prolong the luteal phase of the estrous cycle

Synchronized cyclicity of replacement gilts is crucial to optimize breeding herd management, however, protocols with oral progestogen are expensive and require daily administration. This study tested two synchronization protocols without progestogens during the luteal phase in gilts. In Experiment I, on the day of the expression of the third estrus (D0), gilts were assigned to three groups (n = 6, each): control, with no treatment; PGF25: in which gilts received two doses of hCG (1,500 IU each) on D12 and D15 and two doses of a prostaglandin F2α (PGF) analogue (sodium cloprostenol; 250 µg) 6-h apart, on D25; and PGF30: in which gilts received two doses of hCG (1,500 IU each) on D12 and D15 and two doses of the PGF analogue (sodium cloprostenol; 250 µg) 6-h apart, on D30. The interval between PGF treatment and estrus expression was shorter in PGF30 than in PGF25 (P < 0.01). The PGF treatment failed to decrease serum progesterone (P4) for gilts from the PGF25 group (P > 0.05), but it was effective for gilts in the PGF30 group (P = 0.01). In Experiment II, gilts were assigned to three groups (n = 12, each): control (no treatment); eCG+hCG (400 IU eCG on D10 plus 500 IU hCG on D12); and hCG2 (two hCG doses, 1,500 IU each on D12 and D15). On D30, gilts from eCG+hCG and hCG2 that did not express estrus received two doses of the PGF analogue (250 µg each, 6-h apart). All gilts were inseminated when estrus was detected. Serum P4 concentrations were similar for all groups on D10 (P > 0.05) and greater on D20 and D25 for gilts in eCG+hCG and hCG2 (P < 0.01) than for those in the control, whereas P4 concentration was greater in hCG2 than in eCG+hCG, on both moments. The inter-estrus interval (IEI) was shorter for control gilts and intermediate for gilts in eCG+hCG, while the longest IEI was observed for gilts in hCG2 (P < 0.01). Total litter size was larger for gilts in the control (P = 0.02) compared to those in hCG2 and did not differ from the other groups for gilts in eCG+hCG (P > 0.05). In conclusion, Experiment I showed that PGF treatment did not induce luteolysis 10 days after the second hCG treatment but it was effective 15 days after the second hCG application. Additionally, Experiment II showed that both eCG+hCG and hCG2 were efficient in prolonging the luteal phase; however, number of piglets born alive and total litter size were negatively affected by the hCG2 protocol. In this sense, treatment with eCG+hCG or hCG2 may represent a steroid-free approach to prolong the luteal phase in gilts, although the doses and number of treatments must be further investigated.

Novel insights into perfluorinated compound-induced hepatotoxicity: Chronic dietary restriction exacerbates the effects of PFBS on hepatic lipid metabolism in mice

Perfluorobutane sulfonates (PFBS) have garnered extensive utilization because of their distinctive physicochemical properties. The liver acts as a key target organ for toxicity within the body and is vital for regulating metabolic processes, particularly lipid metabolism. However, there is currently a significant research gap regarding the influences of PFBS on hepatic lipid metabolism, especially in individuals with different dietary statuses. Here, the objective of this research was to examine the effects of PFBS on hepatic function under different dietary conditions. The results suggested that the levels of liver injury biomarkers were significantly upregulated, e.g., transaminase (GPT, GOT), while liver lipid levels were downregulated after exposure to PFBS at concentration of 50 μg/L for 42 days. Moreover, restricted diet further intensified the adverse effects of PFBS on the liver. Metabolomics analysis identified significant alterations in lipid-related metabolites in PFBS-induced hepatotoxicity, PFBS exposure induced a decrease in lysophosphatidylethanolamine and lysophosphatidylcholine. PFBS exposure caused an increase in aldosterone and prostaglandin f2alpha under restricted diet. In PFBS treatment group, histidine metabolism, beta-alanine metabolism, and arginine biosynthesis were the main pathway for PFBS toxicity. Aldosterone-regulated sodium reabsorption as a vital factor in inducing PFBS toxicity in the RD-PFBS treatment group. The analysis of 16S rRNA sequencing revealed that exposure to PFBS resulted in imbalance of gut microbial communities. PFBS exposure induced a decrease in Akkermansia and Lactobacillus, but an increase in Enterococcus. PFBS exposure caused the abundance of Lachnospiraceae_NK4A136_group was significantly elevated under restricted diet. Additionally, disruptions in the expression of genes involved in lipid production and consumption may significantly contribute to lipid imbalance in the liver. This study underscores the importance of recognizing the harmful impact of PFBS on liver function, along with the biotoxicity of contaminant influenced by dietary habits.

Ovarian and uterine arteries blood flow velocities waveform, hormones and nitric oxide in relation to ovulation in cows superstimulated with equine chorionic gonadotropin and luteolysis induction 10 and 17 days after ovulation

To investigate the ovarian responses, ovarian and uterine hemodynamics, circulating ovarian hormones, and nitric oxide (NO) with their relations in superstimulated cows. Eight Holstein Friesian dry cows previously synchronized with CIDR underwent rectal Doppler ultrasound scanning and blood sampling after administrating eCG (1500 I.U) on day 10 of the second ovulation (day -5). Cows were treated with 12.5 mg prostaglandin F2α (PGF2α) on days 10 and 17 after ovulation. Estradiol, progesterone, and NO were measured. Results showed that from ≥ 13 follicles, five follicles ovulated from both ovaries. The ovulated follicles increased antrum colored area and colored area % till day -1. The developed corpora lutea (CLs) attained similar diameter, area, colored area, and colored area % from day 2 till day 15. The peak point of velocity (PSV) of uterine arteries decreased while that of ovarian arteries increased from day -4 to day 0. Both ovarian arteries diameter, resistance index (RI), PSV, end velocity (EDV) and systolic/diastolic ratio (S/D) positively correlated (P < 0.0001), but their pulsatility index (PI) negatively correlated (P < 0.0001). The uterine arteries PI, RI, PSV, EDV, time average velocity (TAMV) and S/D negatively correlated (P < 0.0001) but their diameters positively correlated. Estradiol increased but progesterone decreased from day -5 till day 0. After ovulation, P4 reached maximum values on day 9 and started to decrease till day 19.NO showed one peak on day -3 and another one from day 3 to day 9. Conclusions: Blood flow of ovarian arteries is different from uterine arteries and depended on pre- or post-ovulation.