Analytical Core C will be responsible for the storage, cataloging, measurement and analysis of hormone concentrations in subject samples, and for the analysis of other analytes. Analytical Core C will be responsible for measurement of hormones and cytokines in the sequential samples collected before, during and after pregnancy in subjects in Projects I and 11. Progesterone, 17p estradiol, Cortisol, aldosterone, relaxin-2, hCG, PGF, s-flt, VEGF, arginine vasopressin (AVP) and plasma renin activity will be measured. In addition, the proinflammatory markers C-reactive protein, lL-6, TNFa, neopterin, and the anti-inflammatory marker IL-10 will be assayed, as well the markers of endothelial activation, E-selectin and cellular fibronectin. Clinical assay systems will be used to measure plasma protein, sodium, potassium, osmolality, uric acid, serum creatinine, hematocrit and hemoglobin, and 24h urinary creatinine and osmolality. Plasma protein, hematocrit, hemoglobin, and osmolality are indirect measures of maternal volume status; these values normally decrease in pregnancy. Similarly hormones involved in fluid homeostasis in pregnancy, AVP, PRA, aldosterone and Cortisol, will be measured to assess volume adaptive mechanisms. Plasma uric acid and 24-hr endogenous creatinine clearance will be used as indices of renal function. Plasma free VEGF, sfIt (soluble VEGF receptor-1), PGF, s-endoglin and hCG have been suggested as markers of placental function and/or perfusion. Thus the results of assays performed in this core will be essential for the interpretation of the underlying mechanisms of any pathophysiologic finding and they will be correlated with various functional endpoints measured in Projects I and II. The Analytical Core C will also measure relaxin, hCG, estradiol progesterone and 17 OH-progesterone in samples from subjects enrolled in Project 111 as markers of luteal function, and as possible correlates of observed endpoints, and a subset of other hormones and/or pro- and anti-inflammatory markers; the specific secondary biomarkers which will be determined retrospectively guided by results in patients in Projects I and 11. Core C will assure that appropriate quality controls are run in all assays, that samples are correctly batched, and that the data are archived.
This project will provide novel insights into the maternal physiology of normal, spontaneously conceived and ART pregnancy, as well as adverse outcomes after ART. Analytical Core C will provide critical data in assessing the physiology or pathophysiology of these pregnancies by determining changes in honnones and biomarkers of pregnancy (luteal and placental), renal function, fluid balance, inflammation, and endothelial dysfunction.
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