Phosphoinositide 3-Kinase (PI3K) Subunit p110δ Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Fetal Growth Retardation/*genetics ; Neovascularization, Physiologic/*genetics ; Phosphatidylinositol 3-Kinases/*genetics ; Placenta/*blood supply ; Placentation/*genetics ; Trophoblasts/*cytology; Animals ; Cell Differentiation/genetics ; Class I Phosphatidylinositol 3-Kinases ; Disease Models, Animal ; Female ; Litter Size/genetics ; Male ; Matrix Metalloproteinase 12/biosynthesis ; Matrix Metalloproteinase 2/biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pregnancy

Maternal PI3K p110δ has been implicated in smaller litter sizes in mice, but its underlying mechanism remains unclear. The placenta is an indispensable chimeric organ that supports mammalian embryonic development. Using a mouse model of genetic inactivation of PI3K p110δ (p110δ(D910A/D910A)), we show that fetuses carried by p110δ(D910A/D910A) females were growth retarded and showed increased mortality in utero mainly during placentation. The placentas in p110δ(D910A/D910A) females were anomalously anemic, exhibited thinner spongiotrophoblast layer and looser labyrinth zone, which indicate defective placental vasculogenesis. In addition, p110δ was detected in primary trophoblast giant cells (P-TGC) at early placentation. Maternal PI3K p110δ inactivation affected normal TGCs generation and expansion, impeded the branching of chorioallantoic placenta but enhanced the expression of matrix metalloproteinases (MMP-2, MMP-12). Poor vasculature support for the developing fetoplacental unit resulted in fetal death or gross growth retardation. These data, taken together, provide the first in vivo evidence that p110δ may play an important role in placental vascularization through manipulating trophoblast giant cell.

Erratum in: Sci Rep. 2020 Apr 20;10(1):6906. (PMID: 32312994)

Mol Reprod Dev. 1993 Apr;34(4):357-68. (PMID: 8471259)
J Clin Invest. 2010 Apr;120(4):1016-25. (PMID: 20364099)
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4330-5. (PMID: 9113989)
Placenta. 2014 Jul;35(7):450-4. (PMID: 24836459)
Placenta. 2005 Apr;26 Suppl A:S3-9. (PMID: 15837063)
Placenta. 2003 Feb-Mar;24(2-3):219-26. (PMID: 12566249)
Reproduction. 2014 Apr 08;147(5):639-48. (PMID: 24472816)
Dev Biol. 1993 Aug;158(2):475-86. (PMID: 8393815)
Placenta. 2012 Feb;33 Suppl:S92-8. (PMID: 22061678)
Blood. 2011 Apr 21;117(16):4323-7. (PMID: 21378270)
Development. 2008 Jun;135(12):2083-91. (PMID: 18448564)
Dev Biol. 1997 Oct 1;190(1):55-65. (PMID: 9331331)
Development. 1994 Nov;120(11):3257-66. (PMID: 7720565)
J Morphol. 1988 Dec;198(3):341-51. (PMID: 3221406)
J Clin Invest. 2003 Mar;111(5):649-58. (PMID: 12618519)
Sci Rep. 2015 Aug 14;5:13237. (PMID: 26272398)
Development. 1995 May;121(5):1283-99. (PMID: 7789261)
Placenta. 2013 Jul;34(7):518-25. (PMID: 23664004)
J Clin Invest. 2000 Mar;105(5):577-87. (PMID: 10712429)
Nat Genet. 2000 Jul;25(3):311-4. (PMID: 10888880)
Annu Rev Biochem. 2001;70:535-602. (PMID: 11395417)
Placenta. 1980 Jan-Mar;1(1):3-19. (PMID: 7443635)
Genes Dev. 2001 Apr 1;15(7):833-8. (PMID: 11297507)
EMBO J. 2003 Feb 3;22(3):372-84. (PMID: 12554639)
Hypertens Pregnancy. 2005;24(2):103-15. (PMID: 16036395)
Mol Cell Endocrinol. 2002 Feb 22;187(1-2):207-12. (PMID: 11988329)
J Anim Sci. 1995 Jun;73(6):1839-51. (PMID: 7545661)
Mol Endocrinol. 2002 Jul;16(7):1469-81. (PMID: 12089343)
Sci Rep. 2015 Aug 26;5:13371. (PMID: 26306915)
J Biol Chem. 2000 Feb 25;275(8):6022-9. (PMID: 10681597)
Endocrinology. 2009 May;150(5):2413-8. (PMID: 19179443)
Endocrine. 2003 Jul;21(2):123-32. (PMID: 12897374)
J Biol Chem. 1997 Aug 1;272(31):19236-41. (PMID: 9235916)
Placenta. 1996 Jul-Aug;17(5-6):277-89. (PMID: 8829210)
Physiology (Bethesda). 2005 Jun;20:180-93. (PMID: 15888575)
Reproduction. 2011 Apr;141(4):529-40. (PMID: 21273368)
Dev Dyn. 2003 Jun;227(2):185-91. (PMID: 12761846)
Placenta. 2004 Feb-Mar;25(2-3):127-39. (PMID: 14972445)
BJOG. 2004 Sep;111(9):931-9. (PMID: 15327607)
Genes Dev. 2000 Dec 15;14(24):3191-203. (PMID: 11124810)
Am J Obstet Gynecol. 1970 Jan 1;106(1):30-8. (PMID: 5460660)
Science. 1997 Sep 12;277(5332):1669-72. (PMID: 9287221)
J Clin Immunol. 2014 Apr;34(3):272-6. (PMID: 24610295)
Dev Biol. 2005 Aug 1;284(1):12-24. (PMID: 15963972)
J Anim Sci. 1986;62 Suppl 2:47-61. (PMID: 3533875)
Theriogenology. 2013 Jan 1;79(1):94-102. (PMID: 23117132)
Am J Pathol. 2010 Oct;177(4):2103-15. (PMID: 20802175)
Tsitologiia. 2004;46(7):640-8. (PMID: 15473375)
Trends Genet. 1995 Mar;11(3):87-93. (PMID: 7732578)
FEBS Lett. 2009 May 19;583(10):1611-8. (PMID: 19393651)
Dev Biol. 2013 Oct 1;382(1):136-48. (PMID: 23911870)
Science. 1994 Dec 2;266(5190):1508-18. (PMID: 7985020)
EXS. 2012;103:209-79. (PMID: 22642194)
Nature. 2004 Oct 21;431(7011):1007-11. (PMID: 15496927)
Reproduction. 2010 Jul;140(1):165-74. (PMID: 20400519)
J Immunol. 2014 Apr 15;192(8):3958-68. (PMID: 24634494)
Nat Genet. 1998 Mar;18(3):271-5. (PMID: 9500551)
Science. 1998 Dec 11;282(5396):2072-5. (PMID: 9851926)
Science. 1995 Jan 13;267(5195):246-9. (PMID: 7809630)
Mol Cell Biol. 2002 Dec;22(24):8709-20. (PMID: 12446788)
Front Biosci. 2007 Jan 01;12:2484-93. (PMID: 17127257)
Int J Dev Biol. 2010;54(2-3):341-54. (PMID: 19876834)
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5082-7. (PMID: 9560232)
Cell Rep. 2015 Dec 29;13(12 ):2817-28. (PMID: 26711346)
Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):368-77. (PMID: 25503990)
Dev Biol. 2004 Jul 1;271(1):26-37. (PMID: 15196947)
Tsitologiia. 2002;44(11):1058-67. (PMID: 12561726)
Science. 2002 Aug 9;297(5583):1031-4. (PMID: 12130661)
Cell. 1998 Oct 30;95(3):379-91. (PMID: 9814708)
Biol Reprod. 2000 Nov;63(5):1390-5. (PMID: 11058543)
Differentiation. 2005 Dec;73(9-10):452-62. (PMID: 16351689)
Br J Obstet Gynaecol. 1977 Sep;84(9):656-63. (PMID: 911717)
Nat Rev Genet. 2001 Jul;2(7):538-48. (PMID: 11433360)
Mol Hum Reprod. 2000 Oct;6(10):951-8. (PMID: 11006325)
Dev Biol. 2007 Apr 15;304(2):567-78. (PMID: 17289015)
Int Rev Cytol. 1996;165:53-119. (PMID: 8900957)
Mol Endocrinol. 2013 Sep;27(9):1468-82. (PMID: 23820902)
Placenta. 2004 Nov;25(10):829-33. (PMID: 15451198)
Domest Anim Endocrinol. 2004 Oct;27(3):199-217. (PMID: 15451070)
Placenta. 2003 Feb-Mar;24(2-3):123-30. (PMID: 12596737)
J Biol Chem. 2012 Dec 14;287(51):42685-94. (PMID: 23071113)
Neuro Endocrinol Lett. 2010;31(2):193-7. (PMID: 20424580)

EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
EC 2.7.1.137 (Pik3cd protein, mouse)
EC 3.4.24.24 (Matrix Metalloproteinase 2)
EC 3.4.24.24 (Mmp2 protein, mouse)
EC 3.4.24.65 (Matrix Metalloproteinase 12)
EC 3.4.24.65 (matrix metallopeptidase 12, mouse)

Date Created: 20160617 Date Completed: 20180522 Latest Revision: 20201209

20240829

PMC4910077

10.1038/srep28201

27306493