The placenta is a transient, yet critical organ required for fetal health and development. The bovine placenta is considered grossly cotyledonary and histologically synepitheliochorial [1,2]. Placentomes are localized areas of trophectodermal proliferation within the placenta, formed by the chorionic villi of the fetal cotyledon enmeshing with the corresponding crypts of maternal caruncles [1]. Placentomes serve as vascular attachment sites for exchange of gases, nutrients, and fetal metabolic products. Proper establishment of the vascularity of the placentome is essential for the maternal system to support the developing fetus, and studies have demonstrated that placental transport capacity keeps pace with fetal growth via increasing placental vascularity [[3], [4], [5]]. The vascular density of the maternal tissues increases slowly throughout gestation, while the vascular density of the fetal cotyledons remains constant throughout mid-gestation and increases dramatically during the last group, consistent with exponential fetal growth during this same period [5]. While there is adequate research regarding placental development and vascularization at static time points, there is little research detailing the dynamic changes of the placentome in vivo throughout gestation.

Embryonic and fetal mortality causes significant economic loss in beef cattle production. Many studies have demonstrated that early embryonic mortality (<28 days of gestation) accounts for a large proportion of the loss occurring during gestation [[6], [7], [8]]. Pregnancy loss after day 28 of gestation represents a smaller proportion of mortality; a recent meta-analysis reports that heifers have a greater late embryonic/early fetal mortality rate (8.1%) than cows (5.1%) [9]. However, the economic consequences of late embryonic/early fetal mortality (days 27–100 gestation) are reported to be substantially greater than that of early embryonic mortality due to the significant delay in recognition of pregnancy loss and rebreeding date [10]. In cattle, fetal mortality has been reported to range from 3.2 to 42.7% [[11], [12], [13]]. This loss occurs concurrently with a time of placental development during the fetal period, indicating that placental dysfunction plays a role [13].

Non-invasive methods have been described in human and veterinary medicine to assess placental health and subsequent fetal viability [[14], [15], [16]]. Quantitative measurements of uterine hemodynamics acquired via ultrasonography include uterine arterial blood flow, pulsatile index (PI), resistance index (RI), percent area blood perfusion, summation of integrated pixel densities, and the average integrated pixel densities [16,17]. Some of these parameters allow insights into total uterine hemodynamics and thus partially represent the placenta's functional efficiency. However, currently described methodologies do not account for all uterine blood flow and are potentially more related to the myometrium and endometrium as compared to the whole placentome. Previous studies have demonstrated the effectiveness of uterine hemodynamic measurements in investigation of intrauterine growth restriction (IUGR) associated with maternal nutrient restriction/over-nourishment [14,[18], [19], [20]]. These measurements could be particularly useful in high-risk pregnancies associated with advanced reproduction technologies, including in vitro fertilization or somatic cell nuclear transfer cloning in cattle. Specifically, techniques utilizing placentome blood perfusion may be more representative of changes in uterine blood flow and placental efficiency compared with uterine hemodynamic measures alone.

Beyond hemodynamic measurements of the placenta, circulating concentrations of pregnancy associated glycoproteins (PAGs) have also been used to assess pregnancy viability in cattle [21]. PAGs are members of the aspartic proteinase gene family and are produced by the trophoblast giant cells (TGCs) in the trophectodermal epithelium of the bovine placenta [22]. There are over 20 currently identified bovine PAG (boPAG) family members that are expressed differentially throughout gestation [23]. PAG concentration has been demonstrated to rise throughout gestation, beginning between days 24–28 post-AI and rising rapidly a few weeks prior to parturition [24]. Although the presence of PAGs in maternal blood are a pregnancy biomarker, changes in these concentrations have been directly associated with abnormal placental development and correlated with fetal loss [25,26].

While PAGs are an important pregnancy biomarker, their quantification alone does not provide insight into the pathophysiology of placental insufficiency. Non-invasive utero-placental hemodynamic techniques can help characterize blood flow to the placenta and the developing fetus throughout gestation. Therefore, the objective of this study was to determine the association between placentome blood perfusion and circulating PAG concentrations as they relate to the health of the developing fetus in healthy, nulliparous Angus heifers. We hypothesized that placentome perfusion and PAG concentration will be positively correlated and associated with neonatal outcome.