Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC, United States.
Ansh Labs, Webster, TX, United States.
Clin Chim Acta. 2022 Jan 1;524:96-100. doi: 10.1016/j.cca.2021.12.002. Epub 2021 Dec 5.
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.
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.
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.
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.
TGF-β 超家族成员是希望生育和怀孕期间女性生殖健康的重要生物标志物。已经在女性血清中检测到来自卵巢和/或胎盘的 TGF-β 蛋白,但很少有尝试对其进行非侵入性测量,例如在尿液样本中,并将其与血清浓度进行比较。
我们测量了健康育龄妇女和孕妇(妊娠中期)的配对血清和尿液样本中的抑制素 A、抑制素 B、总抑制素、AMH、激活素 A、激活素 B、激活素 AB、卵泡抑素、GDF-9/BMP-15 复合物和 GDF-15。
我们在怀孕和未怀孕的女性的血清中都检测到了所有激素。与未怀孕的女性相比,怀孕的女性中抑制素 A、总抑制素、激活素 A、激活素 AB、卵泡抑素和 GDF-15 显着升高。GDF-15 是唯一在尿液中始终检测到的激素。我们还首次测量了 GDF-9/BMP-15 功能性异二聚体和携带 H202D 多态性的 GDF-15 蛋白。
我们报告了成功测量血清中 GDF-9/BMP-15 异二聚体(其天然形式)和能够在尿液样本中进行非侵入性测量 GDF-15 的能力。这种新的 GDF-15 测定方法还可以在存在常见遗传变异的情况下捕获抗原。