Complete Genome Sequence of Brucella abortus 68, Isolated from Aborted Fetal Sheep in Ukraine

ABSTRACT The complete genome sequence of Brucella abortus 68, isolated from an aborted sheep fetus in Luhansk, Ukraine, was assembled using Nanopore sequences. Two circular chromosomes totaling 3,281,317 bp (N50, 2,124,943 bp) comprised the complete genome sequence. The strain encodes the fosfomycin antibiotic resistance gene fosX, highlighting the risk of cross-species livestock and human infection.

Developmental programming: gestational testosterone excess disrupts LH secretion in the female sheep fetus

Background Prenatal testosterone (T) excess results in reproductive and metabolic perturbations in female sheep that closely recapitulate those seen in women with polycystic ovary syndrome (PCOS). At the neuroendocrine level, prenatal T-treated sheep manifest increased pituitary sensitivity to GnRH and subsequent LH hypersecretion. In this study, we investigated the early effects of gestational T-treatment on LH secretion and pituitary function in the female sheep fetus. Additionally, because prenatal T effects can be mediated via the androgen receptor or due to changes in insulin homeostasis, prenatal co-treatment with an androgen antagonist (flutamide) or an insulin sensitizer (rosiglitazone) were tested. Methods Pregnant sheep were treated from gestational day (GD) 30 to 90 with either: 1) vehicle (control); 2) T-propionate (~ 1.2 mg/kg); 3) T-propionate and flutamide (15 mg/kg/day); and 4) T-propionate and rosiglitazone (8 mg/day). At GD 90, LH concentrations were determined in the uterine artery (maternal) and umbilical artery (fetal), and female fetuses were euthanized. Pituitary glands were collected, weighed, and protein level of several key regulators of LH secretion was determined. Results Fetal pituitary weight was significantly reduced by prenatal T-treatment. Flutamide completely prevented the reduction in pituitary weight, while rosiglitazone only partially prevented this reduction. Prenatal T markedly reduced fetal LH concentrations and flutamide co-treatment partially restored LH to control levels. Prenatal T resulted in a marked reduction in LH-β protein level, which was associated with a reduction in GnRH receptor and estrogen receptor-α levels and an increase in androgen receptor. With the exception of androgen receptor, flutamide co-treatment completely prevented these alterations in the fetal pituitary, while rosiglitazone largely failed to prevent these changes. Prenatal T-treatment did not alter the protein levels of insulin receptor-β and activation (phosphorylation) of the insulin signaling pathways. Conclusions These findings demonstrate that prenatal T-treatment results in reduced fetal LH secretion, reduced fetal pituitary weight, and altered protein levels of several regulators of gonadotropin secretion. The observations that flutamide co-treatment prevented these changes suggest that programming during fetal development likely occurs via direct androgen actions.

Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus

Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein ( SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.