Novel Investigations to Classify Fetal Growth Restriction in Ovine Models of Reproductive Health

Placental compromise or malnutrition during pregnancy are known risk factors for fetal growth restriction (FGR), causing developmental changes in offspring that can have lifelong health implications in many species. The ewe is a valuable model for human gestational research regarding FGR, as well as an agricultural resource that is also afflicted by FGR. This one-health mission necessarily prioritizes the needs of animal and medical researchers alike. Medical journals have called for a focus on placental pathophysiology, reflecting that 60% of FGR cases in humans are idiopathic, and inconsistently overlapping pathophysiology and varied severity appear to be at play in those with known causes. Focusing on individual etiopathologies has made a significant impact on the field but may represent a missed opportunity to identify underlying commonalities, particularly the progression of placental insufficiency. To address these concerns, we developed a novel surgical procedure to allow placental sampling in early pregnancy without halting gestation, providing evidence of early placental compromise to be compared with subsequent fetal or offspring health. Sham, control, and test ewes fared well through surgery and recovery, and the removal of a singular and central placentome was determined to be achievable in this model. We also studied uterine and fetal tissue blood flow in a nutrient restriction model of FGR. Maternal hemodynamics were not affected. Fetal weights were variable, while fetal organ weights followed “brain sparing” growth patterns. Renal and pancreatic tissue blood flow was lower in undernourished ewes. Cerebral and cardiac blood flow correlated positively with fetal weight. Finally, we assessed serum concentrations of anti-Müllerian hormone in ewes through estrous and controlled ovarian stimulation to establish baselines and comparisons for FGR research and improved industry sheep production. Anti-Müllerian hormone concentrations at various time points were correlated with ovarian response to stimulation. However, variability was too high to rely on singular samples, and ewe baselines need to be better established before measurements of anti-Müllerian hormone can be a valuable resource for sheep. These results will offer new tools and knowledge of the pathophysiologic changes behind FGR, as well as the hormonal events relevant to our top one-health model