0000000000427697

AUTHOR

André Hildebrand

showing 2 related works from this author

Fetuin-B, a liver-derived plasma protein is essential for fertilization.

2013

SummaryThe zona pellucida (ZP) is a glycoprotein matrix surrounding mammalian oocytes. Upon fertilization, ZP hardening prevents sperm from binding to and penetrating the ZP. Here, we report that targeted gene deletion of the liver-derived plasma protein fetuin-B causes premature ZP hardening and, consequently, female infertility. Transplanting fetuin-B-deficient ovaries into wild-type recipients restores fertility, indicating that plasma fetuin-B is necessary and sufficient for fertilization. In vitro fertilization of oocytes from fetuin-B-deficient mice only worked after rendering the ZP penetrable by laser perforation. Mechanistically, fetuin-B sustains fertility by inhibiting ovastacin,…

Malemedicine.medical_specialtyCell Membrane Permeabilitymedicine.medical_treatmentmacromolecular substancesFertilization in VitroBiologyGeneral Biochemistry Genetics and Molecular BiologyMiceHuman fertilizationPregnancyInternal medicinemedicineAnimalsZona pellucidaMolecular BiologyZona Pellucidachemistry.chemical_classificationProteaseOvaryGene Expression Regulation DevelopmentalEmbryoCell BiologyEmbryo TransferEmbryo MammalianSpermFetuinSpermatozoaFetuin-BRecombinant ProteinsCell biologyEnzyme ActivationMice Inbred C57BLmedicine.anatomical_structureEndocrinologychemistryFertilizationMetalloproteasesOocytesGameteFemaleGlycoproteinInfertility FemaleDevelopmental BiologyDevelopmental cell
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Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases

2019

AbstractVertebrate fetuins are multi-domain plasma-proteins of the cystatin-superfamily. Human fetuin-A is also known as AHSG, α2-Heremans-Schmid-glycoprotein. Gene-knockout in mice identified fetuin-A as essential for calcified-matrix-metabolism and bone-mineralization. Fetuin-B deficient mice, on the other hand, are female infertile due to zona pellucida ‘hardening’ caused by the metalloproteinase ovastacin in unfertilized oocytes. In wildtype mice fetuin-B inhibits the activity of ovastacin thus maintaining oocytes fertilizable. Here we asked, if fetuins affect further proteases as might be expected from their evolutionary relation to single-domain-cystatins, known as proteinase-inhibito…

0301 basic medicineProteasesGlycosylationalpha-2-HS-Glycoproteinmedicine.medical_treatmentProteolysislcsh:MedicineAstacoideaMatrix metalloproteinaseArticle03 medical and health sciencesMicePlasma0302 clinical medicinemedicineAnimalsHumansFibrinolysinZona pellucidalcsh:ScienceMammalsMetalloproteinaseMultidisciplinaryProteasemedicine.diagnostic_testChemistrylcsh:RWild typeMetalloendopeptidasesFetuinFetuin-BRecombinant ProteinsCell biology030104 developmental biologymedicine.anatomical_structureMatrix Metalloproteinase 9FertilizationProteolysisMetalloproteasesCattlelcsh:Q030217 neurology & neurosurgery
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