PolyADP-ribosylation is required for pronuclear fusion during postfertilization in mice.
BACKGROUND
During fertilization, pronuclear envelope breakdown (PNEB) is followed by the mingling of male and female genomes. Dynamic chromatin and protein rearrangements require posttranslational modification (PTM) for the postfertilization development.


RESULTS
Inhibition of poly(ADP-ribose) polymerase activity (PARylation) by either PJ-34 or 5-AIQ resulted in developmental arrest of fertilized embryos at the PNEB. PARylation inhibition affects spindle bundle formation and phosphorylation of Erk molecules of metaphase II (MII) unfertilized oocytes. We found a frequent appearance of multiple pronuclei (PN) in the PARylation-inhibited embryos, suggesting defective polymerization of tubulins. Attenuated phosphorylation of lamin A/C by PARylation was detected in the PARylation-inhibited embryos at PNEB. This was associated with sustained localization of heterodomain protein 1 (HP1) at the PN of the one-cell embryos arrested by PARylation inhibition.


CONCLUSIONS
Our findings indicate that PARylation is required for pronuclear fusion during postfertilization processes. These data further suggest that PARylation regulates protein dynamics essential for the beginning of mouse zygotic development. PARylation and its involving signal-pathways may represent potential targets as contraceptives.
Osada
Tomoharu
T
Advanced Medical Science Research Center, Mitsubishi Chemical Medience Corporation, Minato-ku, Tokyo, Japan. osada.tomoharu@mg.medience.co.jp
Ogino
Hideki
H
Hino
Toshiaki
T
Ichinose
Sachiyo
S
Nakamura
Kenji
K
Omori
Akira
A
Noce
Toshiaki
T
Masutani
Mitsuko
M
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D048750:Cell Nucleus Division; D005260:Female; D005306:Fertilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015053:Zygote / Q000166:cytology / Q000378:metabolism
D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases
J Histochem Cytochem. 2002 Jan;50(1):91-8
11748298
Mol Pharmacol. 2005 Sep;68(3):895-904
15976037
Development. 2003 Nov;130(21):5169-77
12944431
N Engl J Med. 2009 Jul 9;361(2):123-34
19553641
Biol Reprod. 2004 Mar;70(3):535-47
14613897
Science. 1998 Nov 20;282(5393):1484-7
9822378
Exp Cell Res. 2008 May 1;314(8):1869-80
18396274
Neurochem Int. 2007 Jan;50(1):203-10
17052800
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14244-8
16179389
Mol Reprod Dev. 1990 May;26(1):90-100
2189447
Breast Cancer Res. 2009;11(6):R78
19891779
Methods Enzymol. 1993;225:516-53
8231872
Mol Biol Cell. 2009 Nov;20(21):4575-85
19759176
Cell. 1990 May 18;61(4):591-602
2188731
Int J Dev Biol. 2002 May;46(3):317-20
12068953
Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-28
16829982
Proc Natl Acad Sci U S A. 1985 Jul;82(14):4727-31
3860820
Hum Reprod. 2003 Mar;18(3):576-82
12615828
Nature. 2004 Dec 2;432(7017):645-9
15577915
J Biochem. 1999 Oct;126(4):748-55
10502684
Dev Biol. 2005 Apr 1;280(1):225-36
15766761
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17699-704
15591342
Bioessays. 1993 Aug;15(8):531-8
8135766
Biochem Cell Biol. 1992 Oct-Nov;70(10-11):856-66
1297351
J Neurochem. 2003 May;85(3):697-708
12694396
J Reprod Fertil. 1968 Nov;17(2):399-401
5749384
Int J Mol Med. 2001 Mar;7(3):255-60
11179503
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15619-24
17893336
Br J Pharmacol. 2000 Jun;130(4):843-50
10864891
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2301-4
10051636
Cell. 1981 Feb;23(2):543-9
6258805
Cell Res. 2003 Oct;13(5):375-83
14672561
EMBO J. 2003 May 1;22(9):2255-63
12727891
Cell. 1980 Jan;19(1):277-87
7357605
Cardiovasc Res. 2009 Jan 1;81(1):98-107
18815186
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7136-41
16627622
Mol Cell. 2007 Jan 26;25(2):297-308
17244536
BMC Mol Biol. 2004 Jun 16;5:4
15200685
Mol Immunol. 2008 Apr;45(7):1863-71
18078995
Nat Rev Mol Cell Biol. 2008 Oct;9(10):815-20
18784729
FASEB J. 2008 Nov;22(11):3853-65
18676401
Cell. 2006 Apr 21;125(2):371-83
16630823
Mol Reprod Dev. 2005 Nov;72(3):329-35
16047391
Cloning Stem Cells. 2002;4(4):363-77
12626100
Mol Cell Biochem. 1994 Sep;138(1-2):5-12
7898475