6533b7defe1ef96bd1276678

RESEARCH PRODUCT

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

Joseph NeulenWalter StöckerAndré HildebrandEileen DietzelYuliya GottenbuschSilke EnsslenThomas VeitingerAngela EgertCora SchäferBenjamin RösingRalf WeiskirchenJennifer WesslingThomas RennéTanja TropartzIrene YiallourosJulia FloehrWilli Jahnen-dechentMarc SpehrHubert SchorleRene TolbaBernd Denecke

subject

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 Biology

description

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, a cortical granula protease known to trigger ZP hardening. Thus, plasma fetuin-B is necessary to restrain protease activity and thereby maintain ZP permeability until after gamete fusion. These results also show that premature ZP hardening can cause infertility in mice.

yearjournalcountryeditionlanguage
2013-04-01Developmental cell
10.1016/j.devcel.2013.03.001https://pubmed.ncbi.nlm.nih.gov/23562279