Anti-PTGS1 monoclonal antibody, clone 6G7/G5

Copy number variation (CNV) represents a major source of genomic variation. We investigated the diversity of CNV distribution using SNP array data collected from a comprehensive collection of geographically dispersed sheep breeds. We identified 24,558 putative CNVs, which can be merged into 619 CNV regions, spanning 197 Mb of total length and corresponding to similar to 6.9% of the sheep genome. Our results reveal a population differentiation in CNV between different geographical areas, including Africa, America, Asia, Southwestern Asia, Central Europe, Northern Europe and Southwestern Europe. We observed clear distinctions in CNV prevalence between diverse groups, possibly reflecting the population history of different sheep breeds. We sought to determine the gene content of CNV, and found several important CNV-overlapping genes (BTG3, PTGS1 and PSPH) which were involved in fetal muscle development, prostaglandin (PG) synthesis, and bone color. Our study generates a comprehensive CNV map, which may contribute to genome annotation in sheep.

Context: Fetal growth restriction (FGR) due to placental dysfunction impacts short-and long-term neonatal outcomes. Abnormal umbilical artery Doppler velocimetry indicating elevated fetoplacental vascular resistance has been associated with fetal morbidity and mortality. Estrogen receptors are regulators of vasomotor tone, and fetoplacental endothelium expresses estrogen receptor-beta (ESR2) as its sole estrogen receptor. Objective: Our objective was to elucidate the mechanism whereby ESR2 regulates placental villous endothelial cell prostanoid biosynthesis. Design and Participants: We conducted immunohistochemical analysis of human placental specimens and studies of primary fetoplacental endothelial cells isolated from subjects with uncomplicated pregnancies. Main Outcome Measures: We evaluated in vivo levels of ESR2 and cyclooxygenase-2 (PTGS2) in villous endothelial cells from fetuses with or without FGR and/or abnormal umbilical artery Doppler indices and in vitro effects of ESR2 on prostanoid biosynthetic gene expression. Results: ESR2 and PTGS2 expression were significantly higher within subjects with FGR with abnormal umbilical artery Doppler indices in comparison with controls (P < 0.01). ESR2 knockdown led to decreased cyclooxygenase-1 (PTGS1), PTGS2, prostaglandin F synthase (AKR1C3), and increased prostacyclin synthase (PTGIS), with opposing results found after ESR2 overexpression (P < 0.05). ESR2 mediates prostaglandin H2 substrate availability and, in the setting of differential regulation of AKR1C3 and PTGIS, altered the balance between vasodilatory and vasoconstricting prostanoid production. Conclusions: Higher ESR2 expression in the placental vasculature of FGR subjects with abnormal blood flow is associated with an endothelial cell phenotype that preferentially produces vasoconstrictive prostanoids. Endothelial ESR2 appears to be a master regulator of prostanoid biosynthesis and contributes to high-resistance fetoplacental blood flow, thereby increasing morbidity and mortality associated with FGR. (J Clin Endocrinol Metab 96: E1558-E1567, 2011)