Usefulness of Maternal and Fetal Parameters for the Prediction of Parturition Date in Dogs

An accurate parturition timing is of key importance for breeders and veterinarians in order to give professional assistance to parturition in dogs. However, pregnancy length calculated from the breeding date has a wide variability. Different parameters and formulas have been described and calculated, as well as their accuracy which is affected by various factors: stage of pregnancy, litter and maternal size. Therefore, the selection of the most appropriate parameter panel poses the challenge of weighing their influences and impact on the overall accuracy. The aim of this review is to analyze the parameters useful for parturition timing, especially their accuracy, and to propose the addition of fetal maturity and criteria for its evaluation to detect readiness for parturition. Parameters, as described in literature, are classified as: (i) maternal parameters, (ii) fetal parameters, (iii) ultrasonographic assessment of maternal and fetal heart rate and blood flow, (iv) parameters indicating fetal maturity. A focus on recently described parameters—such as fetal gastrointestinal motility and fetal lung development detected by quantitative ultrasound—is reported. Currently, the most accurate way to predict parturition day is represented by a prepartum progesterone drop, but the identification of a panel of ultrasonographic parameters combining their significance and their accuracy throughout pregnancy is still needed.

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development. The incidence of BPD remains on the rise, as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of severe BPD. We collected tracheal aspirates (TA) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, FDR &amp;lt; 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD vs. the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extreme premature infants contain miRNA signatures associated with severe BPD. These signatures may serve as biomarkers of disease severity in infants with BPD.

Does fetal leptin and adiponectin influence children’s lung function and risk of wheeze?

Adipocytokines, which are secreted during fetal development by both mothers and fetuses, may influence fetal lung development, but little human data are available. We used data from the HOME Study to investigate the associations of cord blood adipocytokine concentrations with children’s lung forced expiratory volume (FEV1; N = 160) and their risk of wheeze (N = 281). We measured umbilical cord serum adipocytokine concentrations using enzyme-linked immunosorbent assays and FEV1 using a portable spirometer at ages 4 and 5 to calculate the percent predicted FEV1 (%FEV1). Parents completed standardized questionnaires of their child’s wheeze symptoms every 6 months from birth to age 5, then again at ages 6 and 8. We used multivariable linear mixed models and modified Poisson regression with generalized estimating equations to estimate associations of adipocytokine concentrations (log2-transformed) with children’s %FEV1 and the risk of wheeze, respectively, adjusting for sociodemographic, perinatal, and child factors. Cord serum leptin was not associated with children’s %FEV1. Higher cord serum adiponectin concentrations were associated with higher %FEV1 in girls (β = 3.1, 95% confidence interval [CI]: 0.6, 5.6), but not in boys (β = −1.3, 95% CI: −5.9, 3.3) (sex × adiponectin p-value = 0.05). Higher leptin was associated with lower risk of wheeze in girls (RR = 0.74, 95% CI: 0.66, 0.84), but not boys (RR = 0.87, 95% CI: 0.69, 1.11) (sex × leptin p-value = 0.01). In contrast, higher adiponectin concentrations were associated with lower risk of wheeze (RR = 0.84, 95% CI: 0.73, 0.96) in both boys and girls. These data suggest that fetal adipocytokines may impact lung development and function in early childhood. Future studies are needed to confirm these findings and explore the mechanisms underlying these associations.

Impaired Fetal Lung Development can be Rescued by Administration of Extracellular Vesicles Derived from Amniotic Fluid Stem Cells

Incomplete lung development, also known as pulmonary hypoplasia, is a recognized cause of neonatal death and poor outcome for survivors. To date, there is no effective treatment that promotes fetal lung growth and maturation. Herein, we describe a novel stem cell-based approach that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). In experimental models of pulmonary hypoplasia, administration of AFSC-EVs promoted lung branching morphogenesis and alveolarization, and stimulated pulmonary epithelial cell and fibroblast differentiation. This regenerative ability was confirmed in two models of injured human lung cells, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. AFSC-EV beneficial effects were exerted via the release of RNA cargo, primarily miRNAs, that regulate the expression of genes involved in fetal lung development. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application.One Sentence SummaryFetal lung regeneration via administration of extracellular vesicles derived from amniotic fluid stem cells

Physiological Effect of Ghrelin on Body Systems

Ghrelin is a relatively novel multifaceted hormone that has been found to exert a plethora of physiological effects. In this review, we found/confirmed that ghrelin has effect on all body systems. It induces appetite; promotes the use of carbohydrates as a source of fuel while sparing fat; inhibits lipid oxidation and promotes lipogenesis; stimulates the gastric acid secretion and motility; improves cardiac performance; decreases blood pressure; and protects the kidneys, heart, and brain. Ghrelin is important for learning, memory, cognition, reward, sleep, taste sensation, olfaction, and sniffing. It has sympatholytic, analgesic, antimicrobial, antifibrotic, and osteogenic effects. Moreover, ghrelin makes the skeletal muscle more excitable and stimulates its regeneration following injury; delays puberty; promotes fetal lung development; decreases thyroid hormone and testosterone; stimulates release of growth hormone, prolactin, glucagon, adrenocorticotropic hormone, cortisol, vasopressin, and oxytocin; inhibits insulin release; and promotes wound healing. Ghrelin protects the body by different mechanisms including inhibition of unwanted inflammation and induction of autophagy. Having a clear understanding of the ghrelin effect in each system has therapeutic implications. Future studies are necessary to elucidate the molecular mechanisms of ghrelin actions as well as its application as a GHSR agonist to treat most common diseases in each system without any paradoxical outcomes on the other systems.