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Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5 mm followed by gradual removal of intravaginal P4 implants during 18 h and treatment with increasing doses of estradiol benzoate during 48 h to mimic proestrus using high E2 (n = 9) or low E2 (n = 9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2 × 2 factorial design with: high E2 and low P4 (n = 11); high E2 and high P4 (n = 11); low E2 and high P4 (n = 11); low E2 and low P4 (n = 10). At 48 h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48 h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.

In ruminants, uterine pulses of prostaglandin (PG) F2αcharacterize luteolysis, while increased PGE2/PGE1distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2αand PGE1pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1(2 mg PGE1), PGF2α(0.25 mg PGF2α), or PGE1+ PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2αdecreased (P< 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1+ PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1or PGE1+ PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α(PGFM; after PGF2αand PGE1+ PGF2α) and the metabolite PGE (PGEM; after PGE1and PGE1+ PGF2α) demonstrated that PGF2αand PGE1are entering bloodstream after IU infusions. Thus, IU pulses of PGF2αand PGE1allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2αtransport to the CL or PGF2αaction by PGE1resulting in complete inhibition of transcriptomic changes following IU PGF2αpulses.Treatment with PGF2αinduced dramatic changes in expression of 955 genes, based on RNA-Seq after the third PGF2αpulse (FDR < 0.01), whereas simultaneous treatment with pulses of PGE1blocked luteolysis and gene expression induced by PGF2α.

The 5-day CO-Synch is an extensively used TAI protocol; however, it requires multiple administrations of prostaglandin F2α (PGF). The objective of the present study was to evaluate the effect of increasing progesterone (P4) device insertion from 5 to 6 days during a TAI protocol on ovarian dynamics and fertility in beef cows. Suckled beef cows (n = 867) at six locations were randomly assigned to either a 5-day or 6-day CO-Synch. Cows received an intravaginal P4 device (CIDR, Zoetis) and 100 µg of gonadorelin acetate (GnRH, Parnell) on d-9 (6-day) or d-8 (5-day). On d-3 CIDR’s were removed, an estrus detection patch applied (Estrotect, Rockway Inc.) and either one (6-day) or two (5-day) doses of PGF (500 µg of cloprostenol sodium, Estroplan, Parnell) was administered. On d0 (72 h after CIDR removal) all cows received 100 µg of GnRH, estrus expression was evaluated, and AI was performed. Pregnancy was determined by ultrasonography 34 days after TAI. Ovarian dynamics were evaluated in a subset of animals (n = 20) between d-3 and d7 to determine preovulatory follicle size, time of ovulation and corpus luteum (CL) size. Data were analyzed using generalized linear mixed models (SAS 9.4). Cows in the 6-day group tended (P = 0.09) to have a larger maximum follicle diameter (16.2±0.4mm) than cows in the 5-day group (15.0±0.6mm). In addition, CL volume on d7 was greater (P = 0.01) in the 6-day (4302±495mm3) than 5-day (2406±455mm3) group. There were, however, no differences (P = 0.15) in the interval between CIDR removal and ovulation. Cows assigned to the 6-day group had greater (P < 0.05) estrus expression [56.1% (215/385) vs 41.5% (161/388)] and pregnancy rate [54.6% (236/438) vs 47.4% (207/435)] than cows in the 5-day group. In conclusion, extension of the period of P4 device insertion in a prolonged proestrus protocol increases preovulatory follicle size, estrous expression, and fertility to TAI.

Background. SARS-CoV-2 is a newly emerged virus that has spread rapidly, exhibiting tremendous morbidity and mortality. Some potential pharmaceutical targets have been identified but are still lacking proper validation. Case Presentation. We describe the case of a young, immunosuppressed and critically ill patient with previous Influenza B infection, requiring extracorporeal membrane oxygenation, which was then followed, in the succeeding months, by SARS-CoV-2 infection complicated by severe adult respiratory distress syndrome. Her clinical course exhibited complications, including pulmonary embolism, acute kidney injury, pneumothorax, pneumomediastinum, multiple cardiac arrests, and eventually death. Conclusion. Coinfection with other respiratory pathogens and opportunistic infections are possible.