David Christiansen

Evaluation of Systemic Relaxin Blood Profiles in Horses as a Means of Assessing Placental Function in High-Risk Pregnancies and Responsiveness to Therapeutic Strategies

Placental insufficiency is regarded as the primary factor contributing to late‐term abortion and perinatal death of foals. Often when problems associated with late‐term pregnancy in the horse are manifest the condition is well‐advanced and therapeutic intervention may not be effective in rescuing the pregnancy. If a compromised pregnancy due to placental insufficiency could be identified early, the pregnancy might be sustained through medical intervention. Because the placenta is the sole source of circulating relaxin in the mare, we hypothesized that systemic relaxin may serve as a biomarker of placental function and fetal well‐being and a predictor of pregnancy outcome at delivery. To test this hypothesis we monitored plasma relaxin in mares (light breeds) with normal and problematic pregnancies from clinical cases presented to the veterinary hospital and in pregnant mares experimentally inoculated with Streptococcus equi zooepidemicus to induce uterine infection. Upon establishment of placentitis, mares were assigned to different therapeutic strategies and responsiveness was monitored. Blood was collected during the third trimester of pregnancy, and relaxin content was determined using a homologous equine relaxin radioimmunoassay. The results reported here show a positive relationship between low circulating relaxin and poor pregnancy outcome in mares with compromised placental function. While relaxin may have value as a diagnostic assay for identifying mares with high‐risk pregnancies associated with placental dysfunction, the variable results obtained from mares undergoing drug treatment for experimentally induced placentitis make it difficult to determine the reliability of relaxin for evaluating therapeutic efficacy.

Ex vivo bioluminescence imaging of late gestation ewes following intrauterine inoculation with lux-modified Escherichia coli.

Our objectives were to develop an ovine model for Escherichia coli-induced preterm delivery, and monitor E. coli (lux modified for photonic detection) invasion of the fetal environment--ewes (124+/-18d of gestation) received intrauterine inoculations using E. coli-lux as follows: control (n = 5), 1.2 x 10(6) CFU/ml (n = 5), 5.6 x 10(6) CFU/ml (n = 5) E. coli-lux. Preterm delivery occurred between 48 and 120 h post-inoculation in 60%, 60% of ewes infected with 1.2, and 5.6 x 10(6) CFU/ml E. coli-lux, respectively, with presence of emitting bacteria confirmed by real-time imaging of lamb tissues. In summary, preterm delivery and/or fetal distress were observed in a majority of inoculated ewes. Finally, the use of photonic bacteria with imaging was a feasible means to monitor bacterial presence ex vivo.

Pelvic Floor Biomechanics from Animal Models

Pelvic organ prolapse (POP) is characterized by the failure of vaginal wall support and protrusion of the pelvic organs through the vaginal orifice. The exact etiology of POP remains elusive to date, and one of the primary hurdles is the limited availability of animal models, which provide a means to better understand the weakening of supportive tissues in POP and the mechanisms of treatment failures. Each animal model has its own set of advantages and disadvantages. In this chapter, we review the various animal models of POP and provide an indepth analysis of sheep as a robust large animal model for urogynecological research. The ease of handling, short lifespan, and relatively low costs are major advantages of rodent models, which have been used extensively to investigate connective tissue physiology and pathophysiology as it relates to POP. However, sheep have supporting structures for pelvic organs, as well as structural and mechanical properties more similar to humans. Many of the risk factors for sheep prolapse have close analogues in humans, including high fetal weight, obesity, dystocia, parity, and family history of prolapse. In addition, large animal models, such as sheep, are likely more appropriate for evaluation of novel therapeutic strategies for treatment. Future research using sheep and other animal models will illuminate the pathophysiology of POP as well as provide essential information on pelvic floor biomechanics and treatment efficacy.