Effect of using 200 µg of gonadorelin at the first gonadotropin-releasing hormone of the breeding-Ovsynch on ovulatory response and pregnancies per artificial insemination in first-service lactating Holstein cows.

This study aimed to determine whether 200 µg of GnRH (gonadorelin hydrochloride) would increase ovulatory response and pregnancies per artificial insemination (P/AI) compared with 100 µg at the first GnRH of the breeding-Ovsynch of a Double-Ovsynch program (DO) in lactating Holstein cows. Weekly cohorts of primiparous (n = 719) and multiparous (n = 1,191) cows submitted to DO (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH [G1], 7 d later PGF2α [PG1], 1 d later PGF2α, ∼32 h later GnRH [G2], and ∼16 h later timed artificial insemination [TAI]) for first service, randomly received either 100 µg or 200 µg of GnRH (gonadorelin hydrochloride) at G1 (primiparous, 64-75 DIM; multiparous, 59-70 DIM). Ovulation was determined by ultrasound 2 d after G1 (n = 1,294) and 2 d after G2 (n = 1,020). Blood samples were collected at G1 and at PG1 d to evaluate serum progesterone (P4) concentrations. Conventional (n = 314, Angus; n = 1,084, Holstein) and Holstein sexed semen (n = 276) were used. Pregnancy was diagnosed on d 32, 46, 88, and 200 post-TAI. The high dose of GnRH (200 µg) increased overall ovulatory response to G1 compared with 100 µg (81.3% vs. 65.1%), being similar between parities (primiparous, 72.2%; multiparous, 73.9%). Mean serum P4 concentrations at PG1 did not differ between treatments (100 µg: 9.59 ± 0.15 ng/mL vs. 200 µg: 9.43 ± 0.15 ng/mL). Cows with no ovulation to G1 had higher serum P4 concentrations at G1 than cows with ovulation to G1 (6.27 ± 0.19 ng/mL vs. 4.66 ± 0.07 ng/mL). At PG1, the proportion of cows with functional corpus luteum (98.7% vs. 89.7%) and serum P4 concentrations (9.68 ± 0.12 ng/mL vs. 9.14 ± 0.22 ng/mL) were greater in cows that ovulated to G1 compared with cows that did not ovulate. Also, cows that ovulated to G1 had a greater increase in serum P4 concentrations from G1 to PG1 than cows with no ovulation (5.26 ± 0.12 ng/mL vs. 3.32 ± 0.25 ng/mL). The high dose of GnRH improved overall P/AI at 32 d post-TAI in cows inseminated with conventional semen (54.6% vs. 48.2%) and tended to improve P/AI on 46 (48.8% vs. 44.9%), 88 (47.6% vs. 43.4%), and 200 (45.3% vs. 41.2%) d post-TAI. Primiparous cows inseminated with conventional semen had better P/AI than multiparous cows at d 32 (58.2% vs. 49.4%), 46 (55.1% vs. 44.4%), 88 (53.2% vs. 43.2%) and 200 (51.6% vs. 40.7%) post-TAI. Primiparous cows treated with 200 µg GnRH had lower P/AI on d 32, 46, 88, and 200 post-TAI when inseminated with sexed semen than with conventional semen. In summary, the higher dose of GnRH at G1 improved ovulatory response and P/AI at d 32 post-TAI and tended to improve P/AI at d 46, 88, and 200 post-TAI in cows inseminated with conventional semen. Moreover, the effect of treatment on P/AI in primiparous cows depended on semen type (conventional vs. sexed semen).

Presynchronization with prostaglandin F2α and gonadotropin-releasing hormone simultaneously improved first-service pregnancy per artificial insemination in lactating Holstein cows compared with Presynch-14 when combined with detection of estrus.

This study aimed to determine the effect of 2 simple breeding strategies combining artificial insemination (AI) after detection of estrus (AIED) and timed AI (TAI) on first-service fertility in lactating Holstein cows. Weekly, lactating Holstein cows (n = l,049) between 40 and 46 d in milk (DIM) were randomly assigned to initiate 1 of 2 breeding strategies for first service: Presynch-14 and PG+G. Presynch-14 is a presynchronization strategy with 2 PGF2α treatments 14 d apart with the last PGF2α 14 d before the initiation of the Ovsynch protocol. Cows treated with PG+G receive a simpler presynchronization program that uses PGF2α and GnRH simultaneously 7 d before Ovsynch. In both treatments, cows detected in standing estrus by tail chalk at any time ≥55 DIM were inseminated, and treatment was discontinued (n = 525). Cows completing treatment received TAI from 78 to 84 DIM (n = 526). In a subgroup of cows that received TAI, blood was collected (n = 163) to assess circulating concentrations of progesterone, and ultrasonographic evaluations of ovaries were performed on the day of first GnRH of Ovsynch (n = 162) and PGF2α of Ovsynch (n = 122). The proportion of cows that received TAI was greater for PG+G compared with Presynch-14 (63.5 vs. 31.9%), which increased DIM at first service for cows treated with PG+G compared with Presynch-14 (75.5 ± 0.4 vs. 68.7 ± 0.4). For cows receiving TAI, the ovulatory response to first GnRH of Ovsynch (73.8 vs. 48.8%) and the proportion of cows with functional corpora lutea (92.6 vs. 73.1%) were greater for PG+G than Presynch-14. Cows treated with PG+G had greater overall pregnancy per AI (P/AI) 42 ± 7 d after AI (40.2 vs. 33.6%) and calving per AI (32.1 vs. 25.2%) than Presynch-14. For cows receiving AIED, treatment did not affect P/AI 42 ± 7 d after AI. However, for cows receiving TAI, PG+G increased P/AI compared with Presynch-14 (44.6 vs. 35.2%). Overall, cows receiving TAI had greater P/AI 42 ± 7 d after AI (42.5 vs. 31.5%) and calving per AI (34.1 vs. 23.7%) and decreased pregnancy loss (16.8 vs. 25.2%) than cows receiving AIED. In summary, PG+G increased the proportion of cows receiving TAI and the DIM at first service, P/AI, and calving per AI compared with Presynch-14 when both TAI programs were combined with AIED.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Graduate Student Literature Review: Effects of human chorionic gonadotropin on follicular and luteal dynamics and fertility in cattle.

Circulating progesterone concentrations during the growth of the ovulatory follicle and early embryo development have been positively associated with embryo quality and survival and pregnancy success. As a potent luteotropic agent with LH-like activity, human chorionic gonadotropin (hCG) has been tested in different studies to improve pregnancy outcomes by increasing circulating progesterone concentrations during the growth of the ovulatory follicle or early embryonic development. Nevertheless, hCG has produced inconsistent, contradictory, and intriguing results. Furthermore, recent research indicates that hCG, when used before artificial insemination, may affect physiological events necessary for the ovulation of a viable oocyte. In addition, the use of hCG-inducing accessory corpus luteum during the estrous cycle seems to disturb luteolysis and follicle and luteal dynamics during the estrous cycle. This literature review discusses past and current research exploring the effects of hCG on the estrous cycle characteristics and pregnancy per artificial insemination and embryo transfer.

Lactate modulates cardiac gene expression in mice during acute physical exercise.

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

Lactate modulates cardiac gene expression in mice during acute physical exercise

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.