Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry

Abstract β-Nerve growth factor (NGF) is a neurotrophin that plays a critical role in fetal development during gestation. ProNGF is the precursor form of NGF with a distinct biological profile. In order to investigate the role of NGF and proNGF in pregnant human females, a sensitive and selective imm...

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Main Authors: Jason Walsh, Joe Palandra, Eduward Goihberg, Shibing Deng, Susan Hurst, Hendrik Neubert
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-34695-7
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author Jason Walsh
Joe Palandra
Eduward Goihberg
Shibing Deng
Susan Hurst
Hendrik Neubert
author_facet Jason Walsh
Joe Palandra
Eduward Goihberg
Shibing Deng
Susan Hurst
Hendrik Neubert
author_sort Jason Walsh
collection DOAJ
description Abstract β-Nerve growth factor (NGF) is a neurotrophin that plays a critical role in fetal development during gestation. ProNGF is the precursor form of NGF with a distinct biological profile. In order to investigate the role of NGF and proNGF in pregnant human females, a sensitive and selective immunoaffinity liquid chromatography-tandem mass spectrometry assay was developed and qualified to simultaneously measure the levels of total NGF (tNGF; sum of mature and proNGF) and proNGF using full and relative quantification strategies, respectively. The assay was used to determine serum tNGF and proNGF levels in the three gestational trimesters of pregnancy and in non-pregnant female controls. Mean tNGF ± SD were 44.6 ± 12.3, 42.6 ± 9.3, 65.4 ± 17.6 and 77.0 ± 17.8 pg/mL for non-pregnant, first, second, and third trimesters, respectively, demonstrating no significant increase in circulating tNGF between the control and the first trimester, and a moderate yet significant 1.7-fold increase through gestation. proNGF levels during the first trimester were unchanged compared to control. In contrast to tNGF, however, proNGF levels during gestation remained stable without significant changes. The development of this sensitive, novel immunoaffinity duplexed assay for both tNGF and proNGF is expected to enable further elucidation of the roles these neurotrophins play in human pregnancy as well as other models.
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spelling doaj.art-615dcb64efbb450992ad9c52804055c62023-06-11T11:11:50ZengNature PortfolioScientific Reports2045-23222023-06-0113111010.1038/s41598-023-34695-7Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometryJason Walsh0Joe Palandra1Eduward Goihberg2Shibing Deng3Susan Hurst4Hendrik Neubert5Pfizer Inc.Pfizer Inc.Pfizer Inc.Pfizer Inc.Pfizer Inc.Pfizer Inc.Abstract β-Nerve growth factor (NGF) is a neurotrophin that plays a critical role in fetal development during gestation. ProNGF is the precursor form of NGF with a distinct biological profile. In order to investigate the role of NGF and proNGF in pregnant human females, a sensitive and selective immunoaffinity liquid chromatography-tandem mass spectrometry assay was developed and qualified to simultaneously measure the levels of total NGF (tNGF; sum of mature and proNGF) and proNGF using full and relative quantification strategies, respectively. The assay was used to determine serum tNGF and proNGF levels in the three gestational trimesters of pregnancy and in non-pregnant female controls. Mean tNGF ± SD were 44.6 ± 12.3, 42.6 ± 9.3, 65.4 ± 17.6 and 77.0 ± 17.8 pg/mL for non-pregnant, first, second, and third trimesters, respectively, demonstrating no significant increase in circulating tNGF between the control and the first trimester, and a moderate yet significant 1.7-fold increase through gestation. proNGF levels during the first trimester were unchanged compared to control. In contrast to tNGF, however, proNGF levels during gestation remained stable without significant changes. The development of this sensitive, novel immunoaffinity duplexed assay for both tNGF and proNGF is expected to enable further elucidation of the roles these neurotrophins play in human pregnancy as well as other models.https://doi.org/10.1038/s41598-023-34695-7
spellingShingle Jason Walsh
Joe Palandra
Eduward Goihberg
Shibing Deng
Susan Hurst
Hendrik Neubert
Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
Scientific Reports
title Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
title_full Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
title_fullStr Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
title_full_unstemmed Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
title_short Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry
title_sort analysis of β nerve growth factor and its precursor during human pregnancy by immunoaffinity liquid chromatography tandem mass spectrometry
url https://doi.org/10.1038/s41598-023-34695-7
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