Prostaglandin F2α

Dinoprost(Prostaglandin F2α) tromethamine salt is a naturally occurring prostaglandin used in medicine to induce labor and as an abortifacient.

References:
[1]. Sharma I, et al. Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis. Fertil Steril. 2010 Jun;94(1):63-70. [2]. Coulthard G, et al. Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps. Nature. 2012 Sep 13;489(7415):278-81.

Prostaglandin F2alpha-induced luteolysis involves activation of Signal transducer and activator of transcription 3 and inhibition of AKT signaling in cattle.[Pubmed:28337827]

Mol Reprod Dev. 2017 Jun;84(6):486-494.

Prostaglandin F2alpha (PGF) induces the precipitous loss of steroidogenic capabilities and cellular death in the corpus luteum of many species, yet the molecular mechanisms underlying this event are not completely understood. Signal transducer and activator of transcription 3 (STAT3) was activated in granulosa cells during follicle atresia, whereas AKT is immediately down-regulated in the corpus luteum after PGF treatment in cattle; however, their involvement in both functional and morphological luteolysis in monovular species still need to be determined. Blood samples and corpus lutea were collected from cows before (0) and 2, 12, 24, and 48 hr after PGF treatment on Day 10 of the estrous cycle (4-5 cows per time point). Serum progesterone concentrations decreased by threefold (p < 0.05) within 2 hr, confirming functional luteolysis. The mRNA abundance of the pro-apoptotic gene BAX increased 12-48 hr post-PGF treatment (p < 0.05), while morphological luteolysis was observed 24 and 48 hr after PGF treatment, based on the loss of plasma membrane integrity, reduction of cytoplasmic volume, and pyknotic nuclei. Phosphorylated STAT3 increased, peaking at 12 hr, and remained elevated until 48 hr after PGF treatment. SOCS3 transcript abundance also increased (p < 0.05) starting at 2 hr post-PGF treatment. In contrast, AKT phosphorylation decreased by 12 hr after treatment. Thus, activation of STAT3 and inactivation of AKT signaling are involved in structural regression of the corpus luteum.

Purulent vaginal discharge in grazing dairy cows: Risk factors, reproductive performance, and prostaglandin F2alpha treatment.[Pubmed:28318582]

J Dairy Sci. 2017 May;100(5):3805-3815.

The objectives of this study were to assess the association of a 4-point scale of vaginal discharge score (VDS) with time to pregnancy to define criteria for a practical case of purulent vaginal discharge (PVD) in dairy cows, to test the risk factors for PVD, and, finally, the effect of a dose of PGF2alpha on cure and reproductive performance. In experiment 1, grazing Holstein cows (n = 2,414) had their vaginal discharge scored at approximately 32 d in milk (DIM) on a 4-point scale, the effect of VDS on the hazard of pregnancy by 300 DIM was then assessed to derive a case definition of PVD. Risk factors for PVD and self-cure were also assessed. In experiment 2, grazing Holstein cows (n = 6,326) from 5 herds were checked for PVD at approximately 30 DIM. Cows with PVD were assigned to receive one dose of 500 mug of PGF2alpha analog (Cloprostenol; Ciclase, Syntex SA, Buenos Aires, Argentina) per cow (odd ear tag number) or to remain untreated (even tag number). Cure was declared if cows presented clear normal vaginal discharge (VDS-0) at visit 2 ( approximately 62 DIM). Data were analyzed with Cox's regression and mixed logistic models. In experiment 1, cows with VDS >/=1 had lower hazard of pregnancy and longer calving to pregnancy interval than cows with VDS-0. This finding was not affected by the time at which the diagnosis was performed. Therefore, a cow >/=21 DIM and having VDS >/=1 was used to define a case of PVD. The odds of PVD were greater in primiparous cows compared with multiparous, in cows with abnormal calving compared with those with normal calving, and in those losing BCS peripartum. In experiment 2, PGF2alpha treatment tended to slightly increase the hazard of pregnancy (adjusted hazard ratio = 1.13). Conversely, PGF2alpha had no effect on the odds of cure of PVD [adjusted odds ratio (AOR) = 1.19], pregnancy at first service (AOR = 1.03), or pregnancy by 100 DIM (AOR = 0.89) or 200 DIM (AOR = 1.27). In conclusion, cows with VDS >/=1 can be considered to have PVD because of their lower hazard of pregnancy and longer calving to pregnancy interval (up to 48 d). Important risk factors are parity, calving, and body condition score loss peripartum. Optimal time of diagnosis is >/=28 to 35 DIM because cows experience a high self-cure rate. Self-cure is also affected by parity, prepartum BCS, and VDS. Finally, as treatment with one dose of PGF2alpha had a small effect on the hazard of pregnancy and no effect on clinical cure, its therapeutic use in grazing dairy cows with PVD is not recommended.

Effect of fish meal supplementation on spatial distribution of lipid microdomains and on the lateral mobility of membrane-bound prostaglandin F2alpha receptors in bovine corpora lutea.[Pubmed:28273497]

Domest Anim Endocrinol. 2017 Jul;60:9-18.

This study examined the effects of fish meal supplementation on spatial distribution of lipid microdomains and lateral mobility of prostaglandin F2alpha (FP) receptors on cell plasma membranes of the bovine corpus luteum (CL). Beef cows were stratified by BW and randomly assigned to receive a corn gluten meal supplement (n = 4) or fish meal supplement (n = 4) for 60 d to allow incorporation of fish meal-derived omega-3 fatty acids into luteal tissue. Ovaries bearing the CL were surgically removed between days 10 to 12 after estrus corresponding to approximately day 60 of supplementation. A 200-mg sample of luteal tissue was analyzed for fatty acid content using gas-liquid chromatography (GLC). The remaining tissue was enzymatically digested with collagenase to dissociate individual cells from the tissue. Cells were cultured to determine the effects of dietary supplementation on lipid microdomains and lateral mobility of FP receptors. Luteal tissue collected from fish meal-supplemented cows had increased omega-3 fatty acids content (P < 0.05). Lipid microdomain total fluorescent intensity was decreased in dissociated luteal cells from fish meal-supplemented cows (P < 0.05). Micro and macro diffusion coefficients of FP receptors were greater for cells obtained from fish meal-supplemented cows (P < 0.05). In addition, compartment diameter of domains was larger, whereas resident time was shorter for receptors from cells obtained from fish meal-supplemented cows (P < 0.05). Data indicate that dietary supplementation with fish meal increases omega-3 fatty acid content in luteal tissue causing disruption of lipid microdomains. This disruption leads to increased lateral mobility of the FP receptor, increased compartment sizes, and decreased resident time, which may influence prostaglandin signaling in the bovine CL.

Evaluation of prostaglandin F2alpha versus prostaglandin F2alpha plus gonadotropin-releasing hormone as Presynch methods preceding an Ovsynch in lactating dairy cows: A meta-analysis.[Pubmed:28318589]

J Dairy Sci. 2017 May;100(5):4065-4077.

Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per artificial insemination (P/AI) at first service. Recently, a presynchronization protocol including GnRH and PGF2alpha (Double-Ovsynch; GnRH, 7 d, PGF2alpha, 3 d, GnRH) followed 7 d later by an Ovsynch protocol was introduced to overcome the limitations of PGF2alpha-based protocols for presynchronization of anovular cows and to precisely set up cows on d 7 of the estrous cycle when the Ovsynch is initiated. A systematic review of the literature and a meta-analytical assessment was performed with the objective to compare the reproductive performance of lactating dairy cows presynchronized with these 2 protocols for the first timed AI (TAI) considering parity-specific effects. A fixed or a random effects meta-analysis was used based on the heterogeneity among the experimental groups. Reproductive outcomes of interest were P/AI measured on d 32 (28-42) and pregnancy loss between d 32 and 60 (42-74) of gestation. A total of 25 articles with 27 experimental groups from 63 herds including 21,046 cows submitted to first TAI using either a Presynch-Ovsynch or a Double-Ovsynch protocol were reviewed. Results for P/AI were then categorized by parity if available. Information was available for P/AI for 7,400 and 10,999 primiparous and multiparous cows, respectively. Information regarding pregnancy loss was available for 7,477 cows. In the random effects model for all cows, the overall proportion of P/AI was 41.7% [95% confidence interval (CI): 39.1-44.3; n = 8,213] and 46.2% (95% CI: 41.9-50.5; n = 12,833) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for primiparous cows, the overall proportion of P/AI was 43.4% (95% CI: 36.2-47.7; n = 2,614) and 51.4% (95% CI: 47.4-55.4; n = 4,786) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for multiparous cows, the overall proportion of P/AI was 39.2% (95% CI: 36.2-42.3; n = 3,411) and 41.4% (95% CI: 36.4-46.4; n = 7,588) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. The overall proportion of pregnancy loss was 11.3% (95% CI: 7.6-15.7; n = 3,247) and 11.7% (95% CI: 9.3-14.3; n = 4,230) on d 60 after AI for Presynch-Ovsynch to and Double-Ovsynch, respectively. Substantial heterogeneity existed among the experimental groups regarding P/AI and pregnancy loss. In summary, a benefit was detected for P/AI in primiparous cows presynchronized with a Double-Ovsynch protocol for the first TAI, but this benefit was not observed in multiparous cows.

Involvement of endothelin-1 and its receptors in PGF2alpha-induced luteolysis in the rat.[Pubmed:12211063]

Mol Reprod Dev. 2002 Sep;63(1):71-8.

The possible mediatory role of endothelin-1 (ET-1) in prostaglandin F(2alpha) (PGF(2alpha))-induced luteolysis in the rat was examined. The effect of PGF(2alpha) was tested on day 9 of pregnancy either in vivo, by injecting cloprostenol, an analog of PGF(2alpha) or in vitro, in isolated intact corpora lutea incubated with PGF(2alpha). Luteolysis was confirmed by progesterone determination in the peripheral blood serum or in the culture medium, respectively. Administration of cloprostenol (.0025 mg/rat) induced within 1 hr, a significant fall (from 56.8 to 27.6 ng/ml, P < 0.0001) in serum progesterone concentrations that was associated with an increased expression of the mRNA to ET-1 and its protein product in rat luteal tissue. Elevated level of ET-1 were also determined at the spontaneous regression of the CL, upon parturition. Expression of the ET receptors, ETA and ETB was not affected by cloprostenol. On the other hand, this PGF(2alpha) analog induced expression of luteal VEGF mRNA. In vitro experiments demonstrate that the LH (100 ng/ml)-induced increase in luteal progesterone secretion was reduced by PGF(2alpha) (1 microg/ml). The inhibitory effect of PGF(2alpha) was reversed by BQ123 (10(- 7) M), that is a selective ETA receptor antagonist. We conclude that the PGF(2alpha)-induced elevation in luteal expression of ET-1 combined with the reversal of its luteolytic effect by an ETA receptor antagonist suggest that ET-1 may take part in the PGF(2alpha)-induced luteolysis in the rat.