Madison E Calvert1, Bhanu Kalra2, Amita Patel2, Ajay Kumar2, Natalie D Shaw3. 1. Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC, United States. 2. Ansh Labs, Webster, TX, United States. 3. Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC, United States. Electronic address: Natalie.shaw@nih.gov.
Abstract
BACKGROUND: TGF-β superfamily members are important biomarkers of reproductive health in women desiring fertility and during pregnancy. TGF-β proteins derived from the ovary and/or placenta have been detected in serum in women, but there have been very few attempts to measure them non-invasively, such as in urinary samples, and to compare them to serum concentrations. METHODS: We measured inhibin A, inhibin B, total inhibin, AMH, activin A, activin B, activin AB, follistatin, the GDF-9/BMP-15 complex, and GDF-15 in paired serum and urine samples from healthy reproductive aged women and in pregnant (second trimester) women. RESULTS: We detected all hormones in serum in both pregnant and non-pregnant women. Inhibin A, total inhibin, activin A, activin AB, follistatin, and GDF-15 were significantly higher in pregnant than in non-pregnant women. GDF-15 was the only hormone consistently detected in urine. We also measured, for the first time, the GDF-9/BMP-15 functional heterodimer and the GDF-15 protein harboring the H202D polymorphism. CONCLUSIONS: We report the successful measurement of the GDF-9/BMP-15 heterodimer (its native form) in serum and the ability to measure GDF-15 non-invasively, in urinary samples. This novel GDF-15 assay also captures the antigen in the presence of a common genetic variant.
BACKGROUND: TGF-β superfamily members are important biomarkers of reproductive health in women desiring fertility and during pregnancy. TGF-β proteins derived from the ovary and/or placenta have been detected in serum in women, but there have been very few attempts to measure them non-invasively, such as in urinary samples, and to compare them to serum concentrations. METHODS: We measured inhibin A, inhibin B, total inhibin, AMH, activin A, activin B, activin AB, follistatin, the GDF-9/BMP-15 complex, and GDF-15 in paired serum and urine samples from healthy reproductive aged women and in pregnant (second trimester) women. RESULTS: We detected all hormones in serum in both pregnant and non-pregnant women. Inhibin A, total inhibin, activin A, activin AB, follistatin, and GDF-15 were significantly higher in pregnant than in non-pregnant women. GDF-15 was the only hormone consistently detected in urine. We also measured, for the first time, the GDF-9/BMP-15 functional heterodimer and the GDF-15 protein harboring the H202D polymorphism. CONCLUSIONS: We report the successful measurement of the GDF-9/BMP-15 heterodimer (its native form) in serum and the ability to measure GDF-15 non-invasively, in urinary samples. This novel GDF-15 assay also captures the antigen in the presence of a common genetic variant.
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