It is well established that erythropoiesis occurs first in the yolk sac, then in the liver, subsequently moving to the bone marrow and, in rodents, the spleen during development. The origin of the erythropoietic precursors and some factors suggested to be important for the changing location of erythropoiesis are discussed in this review. Until recently, the major site of erythropoietin (Epo) production in the fetus was thought to be the liver, but studies have shown now that the Epo gene is expressed strongly in the fetal kidney, even in the temporary mesonephros. The metanephric Epo mRNA is upregulated by anemia, downregulated by glucocorticoids, and contributes substantially to circulating hormone levels in hemorrhaged ovine fetuses. Other sites of Epo and Epo receptor production, likely to have important actions during development, are the placenta and the brain.

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Erythropoietin (Epo) gene expression in ovine fetal liver and kidneys was measured by competitive RT-PCR in situations in which fetal glucocorticoid status was altered. Bilateral adrenalectomy at 120 +/- 0.3 days gestation (term is 145-150 days) caused a significant (P < 0.05) 5-fold increase in renal Epo messenger RNA (mRNA) levels at 145 +/- 1 days compared to those in age-matched controls. With cortisol replacement in adrenalectomized fetuses, renal Epo mRNA levels dropped to 17% of this values (P < 0.05). Cortisol infusion (230 micrograms/h for 48 h) at 108 +/- 1 day decreased renal Epo gene expression significantly (P < 0.01) to 23% of the control value; dexamethasone treatment of the ewe at midgestation (0.76 mg/h for 48 h) also decreased fetal, but not adult, renal Epo mRNA levels (to 12% of control value; P < 0.01). Fetal and maternal liver Epo mRNA levels were unaffected by glucocorticoid status at any stage of pregnancy. Thus, glucocorticoids can influence fetal renal, but not maternal, Epo gene expression. In the presence of high concentrations of fetal glucocorticoids, plasma Epo values were consistently 4-5 mU/ml, close to the sensitivity of the assay, whereas in seven adrenalectomized fetuses, the plasma Epo value was 9.1 +/- 1.4 mU/ml.

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We have used competitive reverse transcription and polymerase chain reaction (RT/PCR) to compare the levels of erythropoietin (Epo) mRNA in the liver and kidneys of the sheep fetus at 60, 80, 100, 130, and 140 days of gestation (term = 145 to 150 days). The effect of dexamethasone infusion in the ewe on Epo gene expression in the 60-day fetus was also investigated. Epo mRNA levels were highest at 60 days of gestation, the earliest age studied, in both liver and kidney. In the liver, Epo mRNA expression declined as gestation proceeded. Kidney Epo mRNA was maintained at a high level until 100 days of gestation, declining significantly in the 130-day fetus (P < .01). Treatment of ewes carrying 60-day fetuses with 0.76 mg/h dexamethasone for 48 hours resulted in a significant decrease in fetal plasma Epo values and Epo mRNA levels in both the liver and kidney. In the dexamethasone-treated fetuses, Epo mRNA in the liver was 52% of control values (P < .05), and in the kidney, 33% of control (P < .001). The results suggest that the kidney may play a more important role as a site of Epo synthesis in the early gestation sheep fetus than previously thought. Glucocorticoids may have a role in the regulation of Epo gene expression.

Scholl-type oxidative cyclodehydrogenation reactions were conducted for an anthryl-substituted dibenzo [def,mno]chrysene (DBC) precursor with the intention to prepare anthracene-fused DBCs with extended conjugation. The compound ADBC-1 with one cyclized ring and its two chloro-and oxy-derivatives (ADBC-Cl and ADBC-O) with good stability were successfully isolated and characterized. They showed largely red-shifted absorption spectra and amphoteric redox behavior. XRD analysis revealed that they can be regarded as large polycyclic aromatic hydrocarbons (PAHs) containing [5]helicene substructures with large twist angles of 67.8°-73.7°owing to steric congestion. Further cyclization to form newer CÀ C bonds failed, which can be explained by an open-shell diradical character and high HOMO energy levels of the products according to spinunrestricted DFT calculations. Results and Discussion SynthesisThe synthesis of the key intermediate ADBC was based on a Suzuki coupling-nucleophilic addition-Friedel-Crafts alkylationoxidative dehydrogenation strategy (Scheme 1). Compound 3 (9-bromo-10-mesityl-2,3,6,7-tetramethoxy-anthracene) was facilely synthesized in 49 % yield by Suzuki coupling reaction between excess of 9,10-dibromo-2,3,6,7-tetramethoxyanthra-[a] Q. ADBC-1 and Compound ADBC-Cl. 100 mg (0.0905 mmol) of ADBC was dissolved in 200 mL of anhydrous DCM in a dry reaction flask. Argon gas was purged into the reaction mixture throughout the reaction. A solution of 234.9 mg (1.4487 mmol) of anhydrous ferric chloride in 2 mL of nitromethane was charged into the reaction mixture through a syringe and stirred for 6 hrs at room temperature. Reaction was later quenched by 5 mL of water. Reaction mixture was later washed with 3 × 100 mL of water and the dichloromethane layer was collected and evaporated. The residue was purified by column chromatography (silica gel, DCM/Hexanes = 8 : 1, ADBC-Cl has larger polarity than ADBC-1) and preparative thin-layer chromatography (TLC) to afford ADBC-1 and ADBC-Cl as dark green solids (58.9 mg, 59 % for ADBC-1, and 26.8 mg, 26 % for ADBC-Cl). ADBC-1: 1 H NMR (400 MHz, CD 2 Cl 2 , ppm): δ = 9.66 (d, J = 8.1 Hz, 1H), 8.35 (d, J = 8.2 Hz 1H), 8.13 (d, J = 7.2 Hz, 1H), 8.02-7.96 (m, 2H), 7.81 (t, J = 7.8 Hz, 1H), 7.76 (d, J = 9.3 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 9.1 Hz, 1H), 7.20-4 5 6 7 8

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