When physiology fails: Endocrine and clinical perspectives on complicated pregnancy and parturition outcomes in dogs.

In this review, metabolic, endocrine and molecular dysregulation of canine pregnancy and parturition complications are discussed in a clinical context. The focus on metabolic and hormonal abnormalities of pregnancy includes gestational diabetes mellitus, pregnancy toxemia, hypocalcemia, luteal insufficiency and hypothyroidism, all with potential negative maternal and fetal outcomes. Gestational pseudo-Addisonian crisis, a rather infrequent but severe complication of canine pregnancy with yet unexplained pathophysiology is also presented. While most of these pregnancy complications have long been known, potential gaps in our understanding of their pathophysiology are shown. Complications during parturition affect 5-37% of all canine whelpings, posing a significant risk to the newborns and the mother. This review discusses recent advances about the pathophysiology of primary uterine inertia (PUI), which is the most frequently diagnosed type of dystocia in the bitch. A multifactorial origin of PUI is supported, although clear conclusions applicable to all cases cannot yet be drawn. Lower than normal maternal peripheral oxytocin and blood ionized calcium concentrations, as well as placental dysfunction resulting in decreased prostaglandin F2α production may be involved in its development. Furthermore, PUI has been linked to changes in the expression of several contractility-associated genes and proteins in the uterus, which may cause altered contractility, or alternatively and simultaneously reflect the time-dependent progression of labor. Future studies should focus on the interplay between the placenta, uterus, and the cervix to elucidate the underlying mechanical, endocrine and molecular mechanisms of PUI.