PGF2 Research Articles

Diagnosis of Cystic Endometrial Hyperplasia and Hydrometra in a Pet Goat

This case report includes the clinical utility of ultrasonography, intrauterine endoscopy (hysteroscopy), and computed tomography (CT) in the preoperative evaluation of hydrometra in a pet goat, which did not completely heal with medical therapy using prostaglandin F2α. Ultrasonography revealed an anechoic liquid within the uterine lumen on a percutaneous scan. CT identified an enlarged uterus and right ovary with a cystic follicle-like structure. Hysteroscopy revealed an accumulation of clear fluids within the uterine lumen and a corrugated, thickened endometrial structure. Plasma estradiol-17β (E2) concentrations were found to be higher (41.9 pg/mL) than normal levels, whereas plasma progesterone (P4) concentrations were at normal levels (0.55 ng/mL) during the follicular phase. Histopathological examination of the endometrium removed by biopsy revealed accelerated mucosal secretion with hyperplasia. Ovariohysterectomy was performed 14 days after the initial diagnosis. Immediately before surgery, plasma E2 and P4 levels were 23.4 pg/mL and 18.34 ng/mL, respectively. Histopathological examination of the surgically removed endometrium revealed cystic endometrial hyperplasia in the uterus and follicular cysts in the ovary. Based on these results, the patient was histologically diagnosed with hydrometra, including cystic endometrial hyperplasia, possibly induced by follicular cysts in the ovary. Ultrasonography and intrauterine endoscopy enabled clear visualization of the secreted mucosa within the uterine lumen, whereas CT enabled an effective visualization of an ovary with a cystic follicle structure. Preoperative observations based not only on ultrasonography but also on evaluations, particularly combined with CT and endoscopy, are useful in diagnosing hydrometra and determining the need for ovariohysterectomy in goats.

Effects of Salmonella Typhimurium infection on intestinal flora and intestinal tissue arachidonic acid metabolism in Wenchang chickens

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether arachidonic acid (ARA) metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and ARA metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), lipoxin A4 (LXA4), ± 8(9)-EET, ± 11(12)-EET, and ± 8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (Phospholipase A2 PLA2 and Cyclooxygenase-2 COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including Interferon-γ (IFN-γ), Transforming growth factor-β1 (TGF-β1), Interleukin-4 (IL-4), and Interleukin-6 (IL-6). In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. The present study revealed the structure of cecal flora in S. Typhimurium-infected Wenchang chickens. In addition, this study demonstrated that S. Typhimurium activates the ARA cyclooxygenase metabolic pathway, which in turn mediates the development of intestinal inflammation in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Long-Interval Prostaglandin F2α Combined with GnRH Improves the Estrus Synchronization and Reproductive Performance of Sheep During the Breeding Season

To improve the efficiency of prostaglandin F2α (PG)-based estrus synchronization in sheep, this study assessed the effect of the gonadotropin-releasing hormone (GnRH) included in the long-interval PG treatment regimen for sheep estrus synchronization during the breeding season. In experiment 1, 30 multiparous Mongolian sheep (3–4.5 years old) were randomly divided into three groups. In the progesterone (P4)–equine chorionic gonadotropin (eCG) group (P4-eCG, n = 10), the ewes were synchronized with intravaginal P4 sponges for 14 days, and received an injection of 330 IU of eCG at sponge withdrawal. In the PG group (n = 10), the ewes received two doses of 0.1 mg PG with a 14 day interval. In the PG-GnRH-PG group (n = 10), the ewes were synchronized by two doses of 0.1 mg PG with a 14 day interval like that in the PG group, but received 50 μg of GnRH 7 days after the first injection of PG. It was found that, at the end of treatment, the number of corpus luteum on the ovaries and the concentration of the serum P4 in the PG-GnRH-PG group were significantly higher than that of the PG and P4-eCG groups. In experiment 2, 59 multiparous Mongolian sheep (3–4.5 years old) were assigned to three groups, like in experiment 1 (n = 20, 20 and 19 for the P4-eCG, PG and PG-GnRH-PG groups, respectively). The estrus of ewes in the PG-GnRH-PG group was more synchronous compared to the PG group. After insemination of the estrus ewes, the pregnancy rate was numerically but not significantly higher in the PG-GnRH-PG group than that in the P4-eCG and the PG groups. In a field test, 285 multiparous Hu sheep (3–4.5 years old) were randomly assigned to a P4-eCG group (n = 142) and PG-GnRH-PG group (n = 143). Timed artificial insemination showed no significant differences in the rates of pregnancy and lambing between the PG-GnRH-PG and P4-eCG groups. We conclude that the addition of GnRH in the long-interval PG protocol may improve the efficiency of PG-based estrus synchronization, and would represent a potential alternative to the conventional P4-eCG based protocol during the breeding season in sheep.

Myometrial shortening stimulates contractility: a biomechanical hypothesis for labor onset and progression.

The mechanisms responsible for the onset and progression of labor remain uncertain. Myometrial contractile activity gradually increases until labor onset as a result of a number of intrinsic and hormonal changes, and this a believed to be the essential process responsible for labor. At the same time, the cervix slowly effaces and dilates throughout pregnancy, and these are the only physiologic parameters predictive labor onset. It is feasible that an interaction exists between increasing contractile activity and cervical softening that is responsible for labor onset and progression. The novel biomedical hypothesis presented here is that labor onset and progression rely on a positive feedback loop involving uterine contractility, myometrial shortening, and shortening-related myometrial prostaglandin F2α production, which occurs when contractile force exceeds the resistance to myometrial shortening. Immediately before labor onset and during early labor, first cervical effacement and then dilation allows the cervix to be pulled up over the presenting part, thus permitting myometrium to assume a decreasing percentage of uterine circumference, which enables myometrium to shorten with each uterine contraction. After complete dilation, further shortening is allowed by decreasing uterine volume resulting from fetal egress from the uterus and complete uterine emptying at delivery. Since contractile activity can shorten myometrium and shortening has been shown to increase myometrial prostaglandin F2α production, the ability of myometrial shortening to stimulate contractile activity results in a positive feedback loop that plays an important role in both labor onset and progression. Premature labor occurs whenever this positive feedback loop develops prior to term because of pathologically increased contractile activity or decreased resistance to shortening. Details of this hypothesis and the mechanisms that either resist or allow myometrial shortening are presented, followed by a review of the laboratory and clinical evidence that either supports or appears to contradict this hypothesis.

Reproductive outcomes of lactating dairy cows submitted to first timed artificial insemination protocols with different strategies to induce final ovulation.

The study evaluated strategies for induction of ovulation at the end of timed AI (TAI) protocols initiated after a novel presynchronization strategy. A total of 909 lactating dairy cows from 6 dairy herds initiated a presynchronization protocol on d -15 with an intravaginal progesterone (P4) implant and 7 d later (d -8) were treated with 1.0 mg of estradiol cypionate (EC) and 0.530 mg of cloprostenol sodium (a synthetic analog of prostaglandin F2α; PGF), simultaneously with the P4 implant removal. On d 0, the protocol for synchronization of ovulation was initiated with 16.8 µg of buserelin acetate (a synthetic analog of GnRH) and insertion of a 2.0 g P4 implant, followed by a treatment with 0.530 mg of PGF on d 6, and a second PGF on d 7, concomitant with the P4 implant withdrawal. In Group EC, cows received 1.0 mg of EC on d 7 as an ovulation inducer. In G group, cows received 8.4 µg of GnRH 56 h after the first PGF (16 h before TAI). In Group EC/G, cows received both EC and GnRH. The TAI was performed on d 9 (48 h after P4 withdrawal) in all experimental treatments. There were no differences among treatments on pregnancy per AI (P/AI) on d 31 (40.4%; 367/909). There was a tendency for greater pregnancy loss in G group (19.8%) than in EC (12.2%) and EC/G (10.1%) groups. When the 2 groups that received EC were combined, the pregnancy loss was lower than when cows received only GnRH (11.2% [21/188] vs. 19.8% [17/86]; P = 0.05). There was an interaction between treatment and expression of estrus on P/AI, in which estrus positively affected P/AI in EC (53.3% vs. 20.0%) and EC/G (53.1% vs. 36.7%), but not in G group (41.5% vs. 38.7%). Overall, 81% of the cows had a corpus luteum (CL) on d 0 and 91% at PGF treatment of the breeding protocols. Fertility was greater in cows with CL at the time of the first PGF treatment than in cows without CL (45.9% vs. 17.7%). In summary, the strategies to induce final ovulation resulted in similar fertility despite the different physiological responses, such as expression of estrus, but further research is needed to definitively confirm the relationship between lack of EC and increased pregnancy loss.

SYNCHRONIZATION OF GnRH AND PGF2Α ON THE REPRODUCTIVE PERFORMANCE IN ACEH CATTLE

This study aims to determine the effect of administering gonadotropin-releasing hormone (GnRH) accompanied by prostaglandin F2 alpha (PGF2α) on the reproductive performance of female Aceh cattle. In this study, eight female Aceh cattle were used, divided into two groups, group I (K1, n= 3) which received estrus synchronization treatment with PGF2α and group II (K2, n= 5) which received estrus synchronization treatment with PGF2α (25 mg/cow) and gonadotropin-releasing hormone (GnRH, 100 µg/cow). GnRH injection in K2 was performed 48 hours after PGF2α injection. The estrus displays measured included onset, duration, and intensity of estrus. Blood collection for estrogen examination was taken from day 1 to day 5 after PGF2α injection, while progesterone examination was taken on days 7, 14, and 21 after artificial insemination. Ovarian response and pregnancy examinations were performed using transrectal ultrasonography (USG). Data on estrus appearance and steroid concentration were analyzed using the Mann-Whitney U test, and differences in pregnancy percentage were analyzed using the chi-square test. In contrast, the number of follicles, dominant follicle diameter, and corpus luteum were analyzed using a split-plot test. Oestrus intensity, oestrus onset, oestrus duration, pregnancy percentage, estrogen and progesterone concentrations, ovarian response in class II follicles, class III follicles, and CL size in K1 vs K2 showed no significant differences (P0.05). The effect of time on ovarian response in class III follicles and CL size showed a significant difference (P0.05). In contrast, the interaction between hormone administration and day of treatment on ovarian response in class II follicles, class III follicles, and CL size showed no significant difference (P0.05). Based on the research results, it was concluded that administration of GnRH accompanied by PGF2α tends to increase the reproductive performance of Aceh cattle.

Effect of two different estrus synchronization protocols on pregnancy rate in Blonde D'aquitaine cattle breed reared in Bulgaria

In the study, two protocols for synchronization of estrus and ovulation in seventeen Blonde d’Aquitaine cows reared in Bulgaria are presented. The animals were similar in age (5-6 years), physiological status (non-pregnant with weaned calves, more than 210 days post-calving), and body condition score (average 5 on a 9-point scale). The experiment was conducted on a beef cattle farm near the Danube River at the end of the grazing season. The objective was to investigate the pregnancy rates under different estrus synchronization schemes. Two synchronization schemes with artificial insemination (FTAI – 72 hours) at fixed time were applied. The schemes were based on prostaglandin F2 alpha (PGF2α) and Gonadotropin-Releasing Hormone (GnRH), with one of them using а Progesterone Releasing Intravaginal Device Delta - PRID DELTA. After executing the two protocols, 47.92 ± 12.34% of the Blonde d’Aquitaine cows were confirmed to be pregnant. In the synchronization protocol using PRID DELTA 62.50 ± 17.87% of inseminated cows were pregnant. In the protocol without the device, 33.33 ± 16.94% of inseminated cows were confirmed to be pregnant. Keywords: beef cattle, estrus synchronization, PRID-Synchprotocol

Prostanoid signaling in retinal cells elicits inflammatory responses relevant to early-stage diabetic retinopathy

AbstractInflammation is a critical driver of the early stages of diabetic retinopathy (DR) and offers an opportunity for therapeutic intervention before irreversible damage and vision loss associated with later stages of DR ensue. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown mixed efficacy in slowing early DR progression, notably including severe adverse side effects likely due to their nonselective inhibition of all downstream signaling intermediates. In this study, we investigated the role of prostanoids, the downstream signaling lipids whose production is inhibited by NSAIDs, in promoting inflammation relevant to early-stage DR in two human retinal cell types: Müller glia and retinal microvascular endothelial cells. When cultured in multiple conditions modeling distinct aspects of systemic diabetes, Müller glia significantly increased production of prostaglandin E2 (PGE2), whereas retinal endothelial cells significantly increased production of prostaglandin F2α (PGF2α). Müller glia stimulated with PGE2 or PGF2α increased proinflammatory cytokine levels dose-dependently. These effects were blocked by selective antagonists to the EP2 receptor of PGE2 or the FP receptor of PGF2α, respectively. In contrast, only PGF2α stimulated adhesion molecule expression in retinal endothelial cells and leukocyte adhesion to cultured endothelial monolayers, effects that were fully prevented by FP receptor antagonist treatment. Together these results identify PGE2-EP2 and PGF2α-FP signaling as novel, selective targets for future studies and therapeutic development to mitigate or prevent retinal inflammation characteristic of early-stage DR.

Baicalin alleviates intestinal inflammation and microbial disturbances by regulating Th17/Treg balance and enhancing Lactobacillus colonization in piglets

BackgroundIntestinal inflammation is a common and serious health problem in piglet production, especially enteritis caused by pathogenic Escherichia coli (E. coli). This condition often leads to high mortality, slow weight gain, and significant economic losses.ResultsIn this study, we isolated an E. coli strain, SKLAN202302, from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin. Piglets infected with E. coli exhibited significant reductions in body weight, feed intake, small intestine length, and ileal goblet cell count (P < 0.05), along with deteriorated ileal morphology. However, baicalin supplementation resulted in body weights, feed intake, and intestinal morphology similar to those of the control group. Notably, there was a significant increase in the colonization of Lactobacillus species, particularly Lactobacillus_reuteri, Lactobacillus_amylovorus, and Lactobacillus_johnii, compared to the E. coli group (P < 0.05). At the metabolic and transcriptional levels, E. coli infection increased inflammatory mediators, including eicosanoids (leukotriene F4, prostaglandin F1a, leukotriene E4, thromboxane B2, prostaglandin G2, and PGH2), monosaccharides, and TCA cycle intermediates (oxoglutaric acid, glutaric acid, adipic acid, citric acid, and isocitric acid) in the ileum. It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway (CTLA4, IFN-ALPHA-8, IL12RB2, TRAV3, TRAV16, FOS, and VEGFA), as well as inflammatory factors. Conversely, baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids [including lysoPC (P-18:1(9Z)/0:0), PC (17:0/0:0), lysoPC (16:1(9Z)/0:0), PC (18:0/0:0), lysoPC (18:0/0:0), PA (10:0/i-16:0), and PA (10:0/8:0)] and amino acids. It also regulated genes within the IL-17 signaling pathway (IL4, CCL17, CXCL10, IFNG, and CXCL2), suggesting a mechanism by which baicalin mitigates E. coli-induced intestinal and microbial disturbances. Subsequent flow cytometry analysis showed that E. coli infection increased the numbers of CD3+ and Foxp3+ cells, decreased IL-17A+ cells, and reduced Th17/Treg ratios. Baicalin supplementation restored these parameters to control levels.ConclusionsBaicalin supplementation effectively alleviates E. coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization, counteracting inflammatory mediators, and regulating immune-related gene expression and the Th17/Treg balance. These findings highlight baicalin’s potential in alleviating intestinal inflammation.Graphical abstract

Estrus syncrhonization in ewes with prostaglandins at dif-ferent days post CIDR insertion

Objective: To evaluate the effect of prostaglandin F2α (PGF2α) application on days 0, 3 and 6 of the synchronized luteal phases on reproductive perfomance and its effect on progesterone concentrations of multiparous ewes. Design/methodology/approach: The experimental design was a completely randomized. Seventy-five ewes synchronized with control internal drug release devices (CIDR) for six days and 250 UI of equine chorionic gonadotropin (eCG) were used at device removal. The ewes were randomly distributed in three treatments in relation to the days of application of PGF2α (125 μg sodium cloprostenol): in the first group of ewes, PGF2α was applied at the time of insertion of the CIDR (D0, n=25); in the second group PGF2α was applied on day three of insertion of the CIDR (D3, n=25) and in the third group it was applied on day six, at the time of the withdrawal of the CIDR (D3, n=25). The presentation of estrus and the gestation rate were analyzed through the c2 test. The onset of estrus and prolificacy by a Tukey analysis of variance and comparison of means. The concentration of P4 was carried out using the mixed design procedure, which included fixed effects of treatment and day, and interaction of both. Results: Presentation and onset of estrus were different (P&lt;0.05) between treatments due to the effect of the interval in the days of PGF2α application. The progesterone (P4) concentrations in blood serum showed differences during the synchronized luteal phase (D0: 4.8 ng mL-1; D3: 6.0 ng mL-1, D6: 8.8 ng mL-1). However, no differences were found in gestation rate and prolificacy due to the main effects. Limitations on study/implications: The application of 125 µg of PGF2α on different days of the synchronized luteal phase does not affect gestation rate and prolificacy. Nevertheless, presentation and onset of estrus were different, so it must be considered in laparoscopic artificial insemination programs. Findings/conclusions: The application of PGF2α during the synchronized luteal phase at short intervals showed better results at the end of treatment. The corpus luteum (CL) and CIDR increase P4 concentrations; which modifies the estrus response, and it has a positive effect in reproductive performance.

Bleb Reformation After Lateral Cantholysis in a Case of Prostaglandin-associated Periorbitopathy.

An 84-year-old male with uncontrolled intraocular pressure (IOP), despite maximum topical medications including prostaglandin F2α analog, had bilateral prostaglandin-associated periorbitopathy-related tight upper eyelids. One day after trabeculectomy of the left eyelid, IOP was 24 mm Hg, with a flat bleb. Daily ocular massage failed to maintain bleb filtration. IOP was reduced to 4 mm Hg after lifting the left upper eyelid; hence, ocular compression from a tight upper eyelid was the suspected cause preventing flow from the scleral flap. A lateral cantholysis was performed to release the eyelid pressure. On the first postoperative day, the bleb was documented to be large and diffuse, with subsequent IOP reduction to 10 mm Hg. At the third month of follow-up, the IOP was 8 mm Hg in the left eyelid, with a well-formed bleb.

Effect of Seminal Plasma on the Freezability of Boar Sperm.

Seminal plasma is an important component of semen and has a significant effect on sperm function. However, the relationship between seminal plasma and sperm freezing capacity has not been fully studied. Exploring metabolites and proteins related to the boar sperm freezing capacity in seminal plasma, by metabolomic and proteomic approaches, and directly verifying the protective effect of seminal plasma on the cryopreservation of boar sperm using high and low freezability seminal plasma as base freezing extender. Semen samples were collected from 30 different boars, 11 high and 11 low freezing-resistant boars were selected after freezing 2~4 times, and seminal plasma was selected at the same time. Sperm motility and movement parameters were analyzed using a CASA system. Reproductive hormones (Testosterone, progesterone, estradiol, prolactin, prostaglandin F2α, luteinoid hormone) in seminal plasma were detected by ELISA. Analysis of proteins and metabolites in high and low freezing-resistant seminal plasma by proteomics and metabolomics techniques. The six reproductive hormones tested were not significantly associated with sperm freezing resistance. A total of 13 differentially expressed metabolites (DEMs) and 38 differentially expressed proteins (DEPs) were identified, while a total of 348 metabolites and 1000 proteins were identified. These DEMs were related to energy metabolism, drugs, or environmental pollutants, while the DEPs were mainly involved in the cytoskeletal dynamics and cell adhesion processes. There were 33 metabolites and 70 proteins significantly associated with mean progress motility (PM) at 10 min and 2 h after thawing. The 70 related proteins were associated with cell division and cycle regulation in gene ontology (GO) terms, as well as KEGG pathways, thermogeneration, and pyruvate metabolism. Using highly freezable boar SP as a base freezing extender made no difference from using lowly freezable boar SP, and both were not as good as the commercial control. There were significant differences in seminal plasma with different freezability, but the similarity was much greater than the difference. The protection effect of seminal plasma is not remarkable, and it does not exhibit superior cryoprotective properties compared to commercial semen cryoelongators. This study provides a deeper understanding of how seminal plasma composition affects sperm freezabilty. It provides potential biomarkers and targets for improving sperm cryopreservation techniques.

The effect of PGF2α injection in different times on the pregnancy rate in progesterone-based synchronization in Holstein cows

This study investigated the effect of Prostaglandin F2α (PGF2α) injection at different times on pregnancy rate (PR) in Holstein cows undergoing progesterone-based fixed-time artificial insemination (FTAI). Group 1 (G1, n=30): A progesterone releasing intravaginal device (PRID) was placed intravaginally with a gonadotropin-releasing hormone (GnRH) injection on day 0. Eight days later, PGF2α was injected. PRID was removed on the 9th day, and after 60 hours, FTAI was performed with a GnRH injection. Group 2 (G2, n=30): Unlike G1, PGF2α was injected twice, with an interval of 24 hours, 8 and 9 days after the intravaginal placement of PRID. Group 3 (G3, n=30): PGF2α was injected 9 days after the intravaginal placement of PRID. Pregnancy diagnoses were performed by transrectal ultrasonography 45 days after FTAI. Blood samples were taken on the 8th day (for Groups 1 and 2), the 9th day (for Groups 2 and 3, PRID removal day), and on the day of FTAI (for Groups 1, 2 and 3) and serum progesterone (P4) concentration was determined. The pregnancy rate (PR) was 36.67%, 53.33%, and 43.33% in Groups 1, 2, and 3, respectively (P=0.194). In cows with a body condition score (BCS)

Administering tolfenamic acid to gilts and sows before artificial insemination did not improve litter size but tended to reduce post-service serum prostaglandin F2α levels

Administering tolfenamic acid to gilts and sows before artificial insemination did not improve litter size but tended to reduce post-service serum prostaglandin F2α levels

Latanoprostene bunod: the first nitric oxide-donating antiglaucoma medication.

Glaucoma is a chronic optic neuropathy that causes characteristic visual field defects and is considered one of the leading causes of irreversible vision loss worldwide. Lowering intraocular pressure is the only proven treatment for glaucoma. Medical therapy is usually the first-line treatment for open-angle glaucoma and ocular hypertension. Latanoprostene bunod ophthalmic drop 0.024% is a nitric oxide-donating prostaglandin F2α analog. It lowers the intraocular pressure via a dual mechanism of enhancing aqueous humor outflow through both the trabecular meshwork and uveoscleral pathways. Additionally, the nitric oxide component has shown promise in regulating ocular blood flow and promoting the survival of retinal ganglionic cells. Herein, the mechanism of action, efficacy, safety, and tolerability of the latanoprostene bunod and its effects on ocular blood flow are reviewed. Latanoprostene bunod has demonstrated strong efficacy and a favorable safety profile in both clinical trials and real-world studies. Given the promising results of latanoprostene bunod and advancements in drug delivery, topical fixed-combination and sustained-release formulations containing latanoprostene bunod and other agents targeting different intraocular pressure-lowering mechanisms may become available in the future.

Prostaglandin pathways in equine myometrium regulations: endometrosis progression.

Prostaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function. This study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin-endoperoxide synthase (PTGS2), PGE2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors: PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III). In experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups. We concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors, particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis.

Contractile responses of engineered human μmyometrium to prostaglandins and inflammatory cytokines.

Preterm labor is a prevalent public health problem and occurs when the myometrium, the smooth muscle layer of the uterus, begins contracting before the fetus reaches full term. Abnormal contractions of the myometrium also underlie painful menstrual cramps, known as dysmenorrhea. Both disorders have been associated with increased production of prostaglandins and cytokines, yet the functional impacts of inflammatory mediators on the contractility of human myometrium have not been fully established, in part due to a lack of effective model systems. To address this, we engineered human myometrial microtissues (μmyometrium) on compliant hydrogels designed for traction force microscopy. We then measured μmyometrium contractility in response to a panel of compounds with known contractile effects and inflammatory mediators. We observed that prostaglandin F2α, interleukin 6, and interleukin 8 induced contraction, while prostaglandin E1 and prostaglandin E2 induced relaxation. Our data suggest that inflammation may be a key factor modulating uterine contractility in conditions including, but not limited to, preterm labor or dysmenorrhea. More broadly, our μmyometrium model can be used to systematically identify the functional impact of many small molecules on human myometrium.

Evaluation of prevalence, risk factors, and therapeutic approach for subclinical endometritis and oviductal occlusion in repeat breeder Holstein cattle.

Due to the productive and economic consequences of Repeat Breeder (RB) syndrome, the objectives of this study were to determine the prevalence and risk factors for subclinical endometritis (SE) and oviductal occlusion (OO) in RB cows, and to make a therapeutic approach for these pathologies. In 99 RB cows, endometrial cytologies were performed to assess the presence of SE (>5% polymorphonuclear neutrophils), and the oviductal patency was checked using the phenolsulfonphthalein test. Body condition score was evaluated, and data from each animal were obtained from on-farm software (parity, calving date, artificial insemination (AI) date, number of AI, and occurrence of postpartum diseases). Cows positive to SE were assigned to one treatment protocol: a) Non-steroidal anti-inflammatory drug (NSAID), b) Prostaglandin F2α (PGF2α), c) NSAID+ PGF2α. Similarly, cows with OO were assigned to one treatment: a) Therapeutic embryo, b) Artificial insemination. The prevalence for SE and OO was 22% and 3%, respectively. Regarding SE, the logistic regression did not show any significant difference for the risk factors evaluated. Moreover, cows that were administered the NSAID, either alone or in combination with PGF2α, showed higher conception rates in the following AI (p<0.05). Due to the low prevalence of OO, it was not possible to perform the logistic regression analysis. In conclusion, neither SE nor OO seem to be the main cause of RB syndrome in the cows under study. Additionally, when SE is diagnosed as the main cause of RB syndrome, treatment with NAISDs seems to increase conception rates.

Lipid Imbalance and Inflammatory Oxylipin Cascade at the Maternal-Fetal Interface in Recurrent Spontaneous Abortion

BackgroundRecurrent spontaneous abortion (RSA) is intricately linked to metabolic dysregulation at the maternal-fetal interface during early gestation. Abnormal levels of essential fatty acids and downstream oxylipins in decidua and chorionic villi have been identified as potential risk factors for RSA. Oxylipins have been linked to excessive inflammation, which might disrupt maternal-fetal immune tolerance, potentially contributing to RSA. Nonetheless, the exact fatty acid-oxylipin metabolic pathway at the matrernal-fetal interface in RSA occurrence remains unknown. Therefore, this research aimed to explore the effect of essential fatty acids, their transport, and downstream oxylipins at the maternal-fetal interface on RSA pathogenesis. MethodsPlasma, chorionic villus, and decidual tissue samples from the first trimester were collected from healthy pregnant women undergoing elective pregnancy terminations, as well as from patients experiencing spontaneous abortion. The concentrations of essential fatty acids and their downstream oxylipins in the villi and decidua were quantified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS). The expression of enzymes related to metabolic pathways was investigated by q-PCR. The ratios of M1/M2 macrophages were assessed by flow cytometry (FCM). ResultsThis study found elevated concentrations of omega-6 fatty acids, encompassing arachidonic acid (AA), linoleic acid (LA), and dihomo-gamma-linolenic acid (DGLA) in maternal plasma and chorionic villi, whereas lower concentrations were observed in the decidua, than in samples from normal pregnancies. Further analysis revealed that the transport of these fatty acids was dysregulated at the maternal-fetal interface in RSA women, possibly due to the aberrant expression of the fatty acid translocase (FAT/CD36). In addition, this study revealed that RSA patients displayed higher levels of downstream oxylipins, such as prostaglandin F2a (PGF2a), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) in chorionic villi and decidua. These compounds may contribute to M1 inflammatory macrophage polarization in RSA, thereby forming a highly inflammatory environment and influencing immunomodulation at the maternal-fetal interface. ConclusionThe study revealed alterations in omega-6 fatty acids, CD36 transport, and AA downstream oxylipins in RSA, which in turn promote M1 macrophage polarization. Thus, this research has established a foundation for identifying potential biomarkers for, and providing novel insights into, the diagnosis and pathophysiology of RSA.

Evaluation of efficacy of use of intracervical Foley’s catheter with PGE1 vaginal tablet versus intracervical Foley’s catheter with extra-amniotic instillation of PGF2 alpha for second trimester abortion

Evaluation of efficacy of use of intracervical Foley’s catheter with PGE1 vaginal tablet versus intracervical Foley’s catheter with extra-amniotic instillation of PGF2 alpha for second trimester abortion