Fetuin-B, a liver-derived plasma protein is essential for fertilization
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Fetuin-B, a liver-derived plasma protein is essential for fertilization. / Dietzel, Eileen; Wessling, Jennifer; Floehr, Julia; Schäfer, Cora; Ensslen, Silke; Denecke, Bernd; Rösing, Benjamin; Neulen, Joseph; Veitinger, Thomas; Spehr, Marc; Tropartz, Tanja; Tolba, René; Renné, Thomas; Egert, Angela; Schorle, Hubert; Gottenbusch, Yuliya; Hildebrand, André; Yiallouros, Irene; Stöcker, Walter; Weiskirchen, Ralf; Jahnen-Dechent, Willi.
In: DEV CELL, Vol. 25, No. 1, 15.04.2013, p. 106-12.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Fetuin-B, a liver-derived plasma protein is essential for fertilization
AU - Dietzel, Eileen
AU - Wessling, Jennifer
AU - Floehr, Julia
AU - Schäfer, Cora
AU - Ensslen, Silke
AU - Denecke, Bernd
AU - Rösing, Benjamin
AU - Neulen, Joseph
AU - Veitinger, Thomas
AU - Spehr, Marc
AU - Tropartz, Tanja
AU - Tolba, René
AU - Renné, Thomas
AU - Egert, Angela
AU - Schorle, Hubert
AU - Gottenbusch, Yuliya
AU - Hildebrand, André
AU - Yiallouros, Irene
AU - Stöcker, Walter
AU - Weiskirchen, Ralf
AU - Jahnen-Dechent, Willi
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - The 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.
AB - The 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.
KW - Animals
KW - Cell Membrane Permeability
KW - Embryo Transfer
KW - Embryo, Mammalian
KW - Enzyme Activation
KW - Female
KW - Fertilization
KW - Fertilization in Vitro
KW - Fetuin-B
KW - Gene Expression Regulation, Developmental
KW - Infertility, Female
KW - Male
KW - Metalloproteases
KW - Mice
KW - Mice, Inbred C57BL
KW - Oocytes
KW - Ovary
KW - Pregnancy
KW - Recombinant Proteins
KW - Spermatozoa
KW - Zona Pellucida
U2 - 10.1016/j.devcel.2013.03.001
DO - 10.1016/j.devcel.2013.03.001
M3 - SCORING: Journal article
C2 - 23562279
VL - 25
SP - 106
EP - 112
JO - DEV CELL
JF - DEV CELL
SN - 1534-5807
IS - 1
ER -