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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The trafficking of membrane cholesterol (Chol) in mammals represents key processes in cells function, particularly in sperm physiology since Chol removal is strictly associated with motility gain. Moreover, the involvement of oxidized Chol derivatives, known as oxysterols, has been recently summoned in the regulation of sperm function. The study of sterols dynamic in human sperm is largely hampered by the low sample availability and the inadequate sensitivity of current methods based on chromatographic techniques. In this study we aimed to develop a robust and reliable method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the sperm levels of Chol and major oxysterols 7β-OH-Cholesterol (7β -OHC) and 7-keto-Cholesterol (7-KC). In particular, by finely tuning the reverse-phase chromatography parameters, the unambiguous identification of Chol, 7β -OHC and 7-KC in biological samples was allowed on the bases of their different retention times, accurate m/z determination and natural isotope abundance pattern. Finally, by applying the method on real sperm samples from 12 semen donors, we documented that normozoospermic subjects (total sperm count >39 × 106 cells/ejaculate) showed an underrepresentation of all steroids compared to subjects with oligozoospermia (total sperm count ≤ 39 × 106 cells/ejaculate; respectively P=0.048 for Chol, P=0.006 for 7β-OHC and P=0.001 for 7-KC). These preliminary data suggest further investigation about the impact of disorders of the spermatogenic process on the composition and function of the sperm membrane. sperm membrane spermatogenesis cholesterol oxysterols liquid chromatography mass spectrometry Iva Šabović1 2# Luca De Toni1# Simone Tescari3 Vincenzo De Filippis3 Massimo Menegazzo1 Giuseppe Opocher4 Carlo Foresta1 and Andrea Garolla1* 2017-06-15T14:47:21+05:30 2017-06-15T14:47:22+05:30 2017-06-15T14:47:22+05:30 5 Adobe InDesign CS6 (Windows) uuid:af47f6db-801c-4cdc-a54b-ce634fcf8ce2 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:573F5C66AB51E711A74BFCCB8DEDAD05 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-06-15T14:47:21+05:30 xmp.iid:563F5C66AB51E711A74BFCCB8DEDAD05 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Andrea Garolla, Department of Medicine, Unit of Andrology andMedicine of Human Reproduction, University of Padova, Via Giustiniani, 2,35128 Padova, Italy,Tel: +39-049-8218518; E-mail: andrea.garolla@unipd.it Citation: Šabović I, Toni DL, Foresta C, Garolla A,Menegazzo M, et al. (2017) Detection of Cholesteroland its Oxidized Derivatives in Human SpermMembranes through a Fast and Reliable LC-MSMethod. J Clin Lab Med 2(1): doi http://dx.doi.org/10.16966/jclm.109 Adobe PDF Library 10.0.1 False endstream endobj 317 0 obj <39 106 cells/ejaculate\) showed an underrepresentation of all steroids\ncompared to \ subjects with oligozoospermia \(total sperm count "d 39 106 cells/ejaculate; respectively P=0.048 for Chol, P=0.006 for 7-OHC\n\ and P=0.001 for 7-KC\). These preliminary data suggest further investigation about the impact of disorders of the spermatogenic \ process on the\ncomposition and function of the sperm membrane.)/Title(Detection of Cholesterol and its OxidizedDerivatives in Human Sperm Membranesthrough a Fast and Reliable LC-MS Method)/Trapped/False>> endobj xref 0 1136 0000000000 65535 f 0000250726 00000 n 0000251210 00000 n 0000251235 00000 n 0000256629 00000 n 0000292214 00000 n 0000292249 00000 n 0000462115 00000 n 0000462174 00000 n 0000462657 00000 n 0000462681 00000 n 0000462817 00000 n 0000472882 00000 n 0000472996 00000 n 0000473081 00000 n 0000473141 00000 n 0000473877 00000 n 0000473902 00000 n 0000474038 00000 n 0000481943 00000 n 0000482920 00000 n 0000483937 00000 n 0000484303 00000 n 0000485317 00000 n 0000485696 00000 n 0000485855 00000 n 0000485924 00000 n 0000486008 00000 n 0000498840 00000 n 0000499118 00000 n 0000499283 00000 n 0000499308 00000 n 0000499609 00000 n 0000514807 00000 n 0000515083 00000 n 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<<4356B92E1C48394399A64DCE4B762A62>]>> startxref 116 %%EOF 316 0 obj <>stream application/pdf Detection of Cholesterol and its OxidizedDerivatives in Human Sperm Membranesthrough a Fast and Reliable LC-MS Method © 2017 Toni DL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The trafficking of membrane cholesterol (Chol) in mammals represents key processes in cells function, particularly in sperm physiology since Chol removal is strictly associated with motility gain. Moreover, the involvement of oxidized Chol derivatives, known as oxysterols, has been recently summoned in the regulation of sperm function. The study of sterols dynamic in human sperm is largely hampered by the low sample availability and the inadequate sensitivity of current methods based on chromatographic techniques. In this study we aimed to develop a robust and reliable method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the sperm levels of Chol and major oxysterols 7β-OH-Cholesterol (7β -OHC) and 7-keto-Cholesterol (7-KC). In particular, by finely tuning the reverse-phase chromatography parameters, the unambiguous identification of Chol, 7β -OHC and 7-KC in biological samples was allowed on the bases of their different retention times, accurate m/z determination and natural isotope abundance pattern. Finally, by applying the method on real sperm samples from 12 semen donors, we documented that normozoospermic subjects (total sperm count >39 × 106 cells/ejaculate) showed an underrepresentation of all steroids compared to subjects with oligozoospermia (total sperm count ≤ 39 × 106 cells/ejaculate; respectively P=0.048 for Chol, P=0.006 for 7β-OHC and P=0.001 for 7-KC). These preliminary data suggest further investigation about the impact of disorders of the spermatogenic process on the composition and function of the sperm membrane. sperm membrane spermatogenesis cholesterol oxysterols liquid chromatography mass spectrometry Iva Šabović1 2# Luca De Toni1# Simone Tescari3 Vincenzo De Filippis3 Massimo Menegazzo1 Giuseppe Opocher4 Carlo Foresta1 and Andrea Garolla1* 2017-06-15T14:47:21+05:30 2017-06-15T14:47:29+05:30 2017-06-15T14:47:29+05:30 5 Adobe InDesign CS6 (Windows) uuid:0125a3e8-f55d-4377-bd65-48fe4066c3d7 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:573F5C66AB51E711A74BFCCB8DEDAD05 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-06-15T14:47:21+05:30 xmp.iid:563F5C66AB51E711A74BFCCB8DEDAD05 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Andrea Garolla, Department of Medicine, Unit of Andrology andMedicine of Human Reproduction, University of Padova, Via Giustiniani, 2,35128 Padova, Italy,Tel: +39-049-8218518; E-mail: andrea.garolla@unipd.it Citation: Šabović I, Toni DL, Foresta C, Garolla A,Menegazzo M, et al. (2017) Detection of Cholesteroland its Oxidized Derivatives in Human SpermMembranes through a Fast and Reliable LC-MSMethod. J Clin Lab Med 2(1): doi http://dx.doi.org/10.16966/jclm.109 Adobe PDF Library 10.0.1 False endstream endobj 317 0 obj <39 106 cells/ejaculate\) showed an underrepresentation of all steroids\ncompared to \ subjects with oligozoospermia \(total sperm count "d 39 106 cells/ejaculate; respectively P=0.048 for Chol, P=0.006 for 7-OHC\n\ and P=0.001 for 7-KC\). These preliminary data suggest further investigation about the impact of disorders of the spermatogenic \ process on the\ncomposition and function of the sperm membrane.)/Title(Detection of Cholesterol and its OxidizedDerivatives in Human Sperm Membranesthrough a Fast and Reliable LC-MS Method)/Trapped/False>> endobj 1137 0 obj <>/Metadata 316 0 R/Names 1138 0 R/Outlines 258 0 R/PageMode/UseOutlines/Pages 315 0 R/StructTreeRoot 318 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 316 2 0000946417 00000 n 0000955025 00000 n 1137 1 0000958586 00000 n trailer <]/Prev 116>> startxref 958790 %%EOF