Prognostic value of C-reactive protein in dogs with elevated serum pancreatic lipase immunoreactivity concentrations.

OBJECTIVE: To determine the prognostic value of serum C-reactive protein (CRP) in dogs with pancreatitis. ANIMALS: 503 client-owned animals with pancreatic lipase immunoreactivity (PLI) > 600 µg/L. METHODS: Routine submissions to the Texas A&M Gastrointestinal Laboratory were monitored for canine samples with PLI > 600 µg/L. Clinics were emailed 2 weeks after PLI measurement and asked the following questions: (1) was the dog hospitalized, and (2) is the patient alive? If a response was received, serum CRP concentration was measured using leftover serum. RESULTS: Paired PLI and CRP results were available for 503 dogs. Median PLI was 984 µg/L (range, 603 to 2,001 µg/L); median CRP was 9.9 mg/L (range, 9.9 to 395.3 mg/L; ref: < 10 mg/L). Inpatient care was provided to 136 dogs (27.0%); 49 dogs (9.7%) died or were euthanized. Median PLI values for dogs that died versus survived were similar. Median CRP was higher in hospitalized dogs (36.1 vs 9.9 mg/L; P < .0001) and those that died (37.2 vs 9.9 mg/L; P < .0001). Compared to dogs with CRP < 10 mg/L, those with CRP > 10 mg/L were 5.3 times more likely to die (CI, 2.7 to 10.2) and 5.7 times (CI, 3.7 to 8.7) more likely to be hospitalized. CLINICAL RELEVANCE: In dogs with PLI > 600 µg/L, CRP > 10 mg/L was associated with increased risk of hospitalization or death. This biomarker may provide prognostic information in dogs with evidence of pancreatitis and guide decisions regarding hospitalization or referral.

Dynamic expression patterns of Irx3 and Irx5 during germline nest breakdown and primordial follicle formation promote follicle survival in mouse ovaries.

Women and other mammalian females are born with a finite supply of oocytes that determine their reproductive lifespan. During fetal development, individual oocytes are enclosed by a protective layer of granulosa cells to form primordial follicles that will grow, mature, and eventually release the oocyte for potential fertilization. Despite the knowledge that follicles are dysfunctional and will die without granulosa cell-oocyte interactions, the mechanisms by which these cells establish communication is unknown. We previously identified that two members of the Iroquois homeobox transcription factor gene family, Irx3 and Irx5, are expressed within developing ovaries but not testes. Deletion of both factors (Irx3-Irx5EGFP/Irx3-Irx5EGFP) disrupted granulosa cell-oocyte contact during early follicle development leading to oocyte death. Thus, we hypothesized that Irx3 and Irx5 are required to develop cell-cell communication networks to maintain follicle integrity and female fertility. A series of Irx3 and Irx5 mutant mouse models were generated to assess roles for each factor. While both Irx3 and Irx5 single mutant females were subfertile, their breeding outcomes and ovary histology indicated distinct causes. Careful analysis of Irx3- and Irx5-reporter mice linked the cause of this disparity to dynamic spatio-temporal changes in their expression patterns. Both factors marked the progenitor pre-granulosa cell population in fetal ovaries. At the critical phase of germline nest breakdown and primordial follicle formation however, Irx3 and Irx5 transitioned to oocyte- and granulosa cell-specific expression respectively. Further investigation into the cause of follicle death in Irx3-Irx5EGFP/Irx3-Irx5EGFP ovaries uncovered specific defects in both granulosa cells and oocytes. Granulosa cell defects included poor contributions to basement membrane deposition and mis-localization of gap junction proteins. Granulosa cells and oocytes both presented fewer cell projections resulting in compromised cell-cell communication. Altogether, we conclude that Irx3 and Irx5 first work together to define the pregranulosa cell population of germline nests. During primordial follicle formation, they transition to oocyte- and granulosa cell-specific expression patterns where they cooperate in neighboring cells to build the foundation for follicle integrity. This foundation is left as their legacy of the essential oocyte-granulosa cell communication network that ensures and ultimately optimizes the integrity of the ovarian reserve and therefore, the female reproductive lifespan.