Evidence of Heritable Luteal Insufficiency in Portuguese Water Dogs: A Pedigree-Based Investigation

Abstract

Reproductive failure and pregnancy loss is devastating for dog owners both financially and emotionally. While infectious agents are the most common causes of canine pregnancy loss, hormonal aberrations are insidious as there are often no accompanying symptoms. Hypoluteoidism results in insufficient serum progesterone (P4) concentrations, causing spontaneous abortion as the first symptom. This condition has been documented in dogs, but the underlying pathophysiology is poorly understood. The current literature supports the basis of hypoluteoidism as genetic, although this has not been proven. This is supported by the fact that sporting and working dog groups have lower progesterone concentrations on average throughout gestation compared to other breeds. Devastatingly, there is no genetic test available for early identification of hypoluteoidism. Our clinical Theriogenology team has identified a pedigree of Portuguese Water Dogs (PWDs) in which multi-generational hypoluteoidism has been confirmed. Specifically, two affected individuals (a dam and daughter) have been identified. The two affected individuals were monitored throughout two pregnancies each, in which endogenous serum P4 fell below baseline prior to Day 63 of gestation. Fortunately, as a result of specialty level care, these pregnancies were successfully managed and maintained using a synthetic progestin and intense monitoring, resulting in four successful litters. Interestingly, two unaffected females have also been also identified, which allows us a unique opportunity to investigate the heritability pattern and possible underlying physiology. Using canine whole genome sequencing technologies, and in collaboration with geneticists from the Department of Pathobiology, our team is aiming to identify a causative genetic mutation for hypoluteoidism. Long-term, with a genetic marker identified, we can develop a diagnostic test to screen at-risk individuals, without necessitating a specialist, and identify high-risk pregnancies to ensure proper care during gestation. Luteal phase deficiency (LPD) is the synonymous disorder in humans, and there is currently no definitive diagnosis in women with this condition. Thus, outcomes may be translational and will serve as a springboard to understand of the complex pathophysiology behind premature luteal failure in the canine, and potentially human, species.