WO2020115291A1 - Marqueur pour la détermination de la fertilité de spermatozoïdes - Google Patents

Marqueur pour la détermination de la fertilité de spermatozoïdes Download PDF

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Publication number
WO2020115291A1
WO2020115291A1 PCT/EP2019/084015 EP2019084015W WO2020115291A1 WO 2020115291 A1 WO2020115291 A1 WO 2020115291A1 EP 2019084015 W EP2019084015 W EP 2019084015W WO 2020115291 A1 WO2020115291 A1 WO 2020115291A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample
mxi
spermatozoa
fertility
per
Prior art date
Application number
PCT/EP2019/084015
Other languages
English (en)
Inventor
Melanie von Brandenstein
Barbara KÖDITZ
Jochen Fries
Timo FUNKE
Johannes SALEM
Original Assignee
Universität Zu Köln
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universität Zu Köln filed Critical Universität Zu Köln
Priority to EP19813045.2A priority Critical patent/EP3891507A1/fr
Publication of WO2020115291A1 publication Critical patent/WO2020115291A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/689—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to pregnancy or the gonads
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/36—Gynecology or obstetrics
    • G01N2800/367—Infertility, e.g. sperm disorder, ovulatory dysfunction

Definitions

  • control sample should be understood in the broadest sense.
  • One, two or more control samples can, optionally, be measured in the same test series as one or more samples S.
  • the control samples do, however, not have to be measured in the same test series.
  • the values of the one or both control samples C+ and/or C- may also be already known values that may be, e.g., stored in and obtained from a data base.
  • the control sample C- of spermatozoa of low fertility may preferably obtained from a patient of the same species suffering from oligozoospermia, asthenozoospermia, teratozoospermia, and/or oligo-astheno-teratozoospermia (OAT syndrome) and/or azoospermia and/or any other pathologic state accompanied by low fertility of the spermatozoa, in particular oligozoospermia, asthenozoospermia, teratozoospermia, and/or OAT syndrome. As indicated above, it may, however, also reflect a value determined before.
  • the content may also be defined as mass content (e.g., in micrograms (pg), nanograms (ng) or picograms (pg)) or a mol content (e.g., micromol (pmol), nanomol (nmol), picomol (pmol) or femtomol (fmol)).
  • mass content e.g., in micrograms (pg), nanograms (ng) or picograms (pg)
  • a mol content e.g., micromol (pmol), nanomol (nmol), picomol (pmol) or femtomol (fmol)
  • a mol content e.g., micromol (pmol), nanomol (nmol), picomol (pmol) or femtomol (fmol)
  • a certain amount per spermatozoon per 10 5 , 10 6 , 10 7 , 10 8 , 10 10 spermatozoa or per sample volume e.g., in milliliters (ml)
  • the experimenter may compare the signal intensity found (in the relevant parts containing spermatozoa and precursors thereof) of the testis biopsy of a patient of interest with a comparable testis sample of a well- fertile individual of the same species. Such staining also allows the localization of Mxi in situ. In principle, the use of a radioactively labeled Mxi -specific antibody or antibody fragment may be even used in vivo to localize the Mxi-2 within the body.
  • Mxi-2 may be the gene expression product of Homo sapiens mitogen-activated protein kinase 14 (MAPK14, also MAPK p38 or p38 MAPK), transcript variant 3 (SEQ ID NO: 10):
  • Vim3 is a spliced variant of Vimentin with a unique C-terminal ending.
  • Vim3 is the naturally occurring Vim3 of the species of interest, i.e. , the Vim3 occurring in the spermatozoa comprised in the sample S.
  • NP_001166511.1 The splice variant corresponding to human Vim3 could be easily identified by sequence analysis and identification of homologues.
  • step (ii) of staining intracellular Mxi-2 may be staining with a fluorescently labeled marker and step (iii) is detecting the localization of the Mxi-2 conducted by fluorescence microscopy.
  • Mxi-2 may be concentrated in the sample S prior to being analyzed further.
  • beads coated with a Mxi-2-specific antibody or antibody fragment may be used to obtain higher contents of Mxi-2 from the sample S.
  • exemplarily agarose beads may be used, in particular agarose beads bearing an antibody-binding entity such as, e.g., protein A.
  • an antibody-binding entity such as, e.g., protein A.
  • any other kinds of beads usable from this purpose may be used in this context such as, exemplarily, silica or magnetic beads.
  • the conjugation method may be freely chosen.
  • the method of the present invention is combined with the further step
  • the method comprises the following steps:
  • step (2) classifying the fertility of the sample S determined by step (2) as:
  • Vim3 monoclonal using the last 8 amino acids (RGKHFISL: SEQ ID No: 2) of the unique C-terminal ending of Vim3, Clone 51 , Davids Biotechnologie (Regensburg, Germany) may be used.
  • the ELISA assay was conducted as described above. Samples containing healthy sperm cells (normozoospermia, Normo) were compared with samples containing sperm cells from patients suffering from oligo-astheno-teratozoospermia (OAT) syndrome, from patients suffering from teratozoospermia (Terato), from patients suffering from azoospermia (Azoo), from patients suffering from oligozoospermia (Oligo) and from patients suffering from asthenozoospermia (Astheno).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un procédé de détermination de la fertilité de spermatozoïdes comprenant la détection de l'isoforme 3 de la protéine kinase activée par des mitogènes (Mxi-2). Le procédé peut être un procédé de détermination de la fertilité de spermatozoïdes contenus dans un échantillon S, ledit procédé comprenant la détection de la teneur totale du Mxi-2 dans l'échantillon S. De plus, la présente invention concerne une bandelette réactive utilisable pour ce procédé. La présente invention concerne en outre d'autres procédés et utilisations dans le contexte de la présente invention.
PCT/EP2019/084015 2018-12-06 2019-12-06 Marqueur pour la détermination de la fertilité de spermatozoïdes WO2020115291A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19813045.2A EP3891507A1 (fr) 2018-12-06 2019-12-06 Marqueur pour la détermination de la fertilité de spermatozoïdes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18210761 2018-12-06
EP18210761.5 2018-12-06

Publications (1)

Publication Number Publication Date
WO2020115291A1 true WO2020115291A1 (fr) 2020-06-11

Family

ID=64650260

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2019/084015 WO2020115291A1 (fr) 2018-12-06 2019-12-06 Marqueur pour la détermination de la fertilité de spermatozoïdes

Country Status (2)

Country Link
EP (1) EP3891507A1 (fr)
WO (1) WO2020115291A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997040386A1 (fr) 1996-04-18 1997-10-30 Immucon Inc. Marqueur de sterilite et/ou de fertilite male
US6017692A (en) 1993-01-29 2000-01-25 The General Hospital Corporation Methods of detecting a malignant cell in a biological sample comprising measuring Mxi gene expression alterations
WO2005121803A1 (fr) 2004-06-10 2005-12-22 Ethicon, Inc. Mesure de proteines de cytosquelette et leurs utilisations en diagnostic, pronostic et therapie
WO2014154686A1 (fr) 2013-03-25 2014-10-02 Universität Zu Köln Procédés de diagnostic et de différenciation des oncocytomes et des carcinomes rénaux nocifs, ainsi que les produits et utilisations associés
WO2018185322A1 (fr) 2017-04-06 2018-10-11 Universität Zu Köln Procédé de détermination de la fertilité de spermatozoïdes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6017692A (en) 1993-01-29 2000-01-25 The General Hospital Corporation Methods of detecting a malignant cell in a biological sample comprising measuring Mxi gene expression alterations
WO1997040386A1 (fr) 1996-04-18 1997-10-30 Immucon Inc. Marqueur de sterilite et/ou de fertilite male
WO2005121803A1 (fr) 2004-06-10 2005-12-22 Ethicon, Inc. Mesure de proteines de cytosquelette et leurs utilisations en diagnostic, pronostic et therapie
WO2014154686A1 (fr) 2013-03-25 2014-10-02 Universität Zu Köln Procédés de diagnostic et de différenciation des oncocytomes et des carcinomes rénaux nocifs, ainsi que les produits et utilisations associés
WO2018185322A1 (fr) 2017-04-06 2018-10-11 Universität Zu Köln Procédé de détermination de la fertilité de spermatozoïdes

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
"GenBank", Database accession no. ACA06103.1
"NCBI", Database accession no. NP_001041541.1
"UniProtKB", Database accession no. Q16539
ALMOG ET AL., JOURNAL OF BIOL. CHEM., vol. 283, 2008, pages 14479 - 14490
MOHAMMAD BOZLUR RAHMAN ET AL: "Bovine spermatozoa react to in vitro heat stress by activating the mitogen-activated protein kinase 14 signalling pathway", REPRODUCTION FERTILITY AND DEVELOPMENT, vol. 26, no. 2, 18 January 2013 (2013-01-18), AU, pages 245 - 257, XP055547377, ISSN: 1031-3613, DOI: 10.1071/RD12198 *
PEARSON ET AL., ENDOCRINE REVIEWS, vol. 22, 2001, pages 153 - 183
PEARSON G ET AL: "Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions", ENDOCRINE REVIEWS, BALTIMORE, MD, US, vol. 22, no. 2, 1 April 2001 (2001-04-01), pages 153 - 183, XP002235969, DOI: 10.1210/ER.22.2.153 *
PREECHAKASEDKIT ET AL., BIOSENS BIOELECTRON, vol. 31, no. 1, 2012, pages 562 - 566
RAHMAN ET AL., REPRODUCTION, FERTILITY AND DEVELOPMENT, vol. 26, 2014, pages 245 - 257
TAL ALMOG ET AL: "Identification of Extracellular Signal-regulated Kinase 1/2 and p38 MAPK as Regulators of Human Sperm Motility and Acrosome Reaction and as Predictors of Poor Spermatozoan Quality", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 283, no. 21, 27 March 2008 (2008-03-27), US, pages 14479 - 14489, XP055548198, ISSN: 0021-9258, DOI: 10.1074/jbc.M710492200 *
TAO ET AL., LETT APPL MICROBIOL, vol. 59, no. 2, 2014, pages 247 - 251
THAKKAR ET AL., CANCER INVEST, vol. 29, 2011, pages 113 - 122
WANG ET AL., J VIROL METHODS, vol. 170, no. 1-2, 2010, pages 80 - 85

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