TRPM7-like channels are functionally expressed in oocytes and modulate post-fertilization embryo development in mouse.
The Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality. Nevertheless, the function of TRPM7 in oocytes, eggs and pre-implantation embryos remains unknown. Here, we described an outward rectifying non-selective current mediated by a TRP ion channel in immature oocytes (germinal vesicle stage), matured oocytes (metaphase II eggs) and 2-cell stage embryos. The current is activated by specific agonists and inhibited by distinct blockers consistent with the functional expression of TRPM7 channels. We demonstrated that the TRPM7-like channels are homo-tetramers and their activation mediates calcium influx in oocytes and eggs, which is fundamental to support fertilization and egg activation. Lastly, we showed that pharmacological inhibition of the channel function delays pre-implantation embryo development and reduces progression to the blastocyst stage. Our data demonstrate functional expression of TRPM7-like channels in mouse oocytes, eggs and embryos that may play an essential role in the initiation of embryo development.
Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.|Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus University, Department of Molecular Biology and Genetics, DK-8000 Aarhus C, Denmark.|Department of Biology and Chemistry, Faculty of Basic Sciences, Universidad Católica del Maule, 3480112 Talca, Chile.
Ingrid
I
Carvacho
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Goli
G
Ardestani
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Hoi Chang
HC
Lee
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Kaitlyn
K
McGarvey
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Rafael A
RA
Fissore
Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.|Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus University, Department of Molecular Biology and Genetics, DK-8000 Aarhus C, Denmark.|Aarhus Institute of Advanced Studies (AIAS), Aarhus University, DK-8000 Aarhus C, Denmark.
Karin
K
Lykke-Hartmann
Mol Biol Cell. 2013 May;24(9):1396-410
23468522
Nat Rev Neurosci. 2001 Jun;2(6):387-96
11389472
Mol Hum Reprod. 2014 Nov;20(11):1077-89
25143461
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2894-9
14976260
Reprod Fertil Dev. 2015 Jan;27(2):323-31
24280268
J Cell Sci. 2015 Dec 1;128(23 ):4442-52
26483387
J Biol Chem. 1992 Jun 5;267(16):11196-201
1597455
Mol Reprod Dev. 2012 Nov;79(11):742-56
22888043
Nature. 2002 Jul 11;418(6894):181-6
12077604
J Gen Physiol. 2006 May;127(5):525-37
16636202
Cell Calcium. 2016 Jan;59(1):21-31
26725171
J Cell Biol. 1992 May;117(4):799-811
1577859
J Gen Physiol. 2002 May;119(5):487-507
11981025
J Biol Chem. 1992 Sep 5;267(25):17624-30
1387638
ACS Chem Biol. 2011 Jul 15;6(7):716-23
21526836
Hum Reprod Update. 2008 Sep-Oct;14(5):431-46
18603645
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4169-74
22371584
Nature. 2001 May 31;411(6837):590-5
11385574
Science. 2008 Oct 31;322(5902):756-60
18974357
Development. 2002 Aug;129(15):3533-44
12117804
Science. 2002 Jun 14;296(5575):2046-9
12016205
Science. 2003 Nov 21;302(5649):1416-8
14631046
Circulation. 2013 Jul 9;128(2):101-14
23734001
Cell Rep. 2013 Dec 12;5(5):1375-86
24316078
Cell. 2003 Jul 25;114(2):191-200
12887921
Cell. 2014 May 22;157(5):1061-72
24855944
J Cell Sci. 1995 Jan;108 ( Pt 1):143-51
7738091
Cell. 2010 Apr 16;141(2):331-43
20403327
Nat Commun. 2010 Nov 02;1:109
21045827
Adv Exp Med Biol. 2011;704:173-83
21290295
Pharmacol Rev. 2010 Sep;62(3):381-404
20716668
Exp Cell Res. 1978 May;113(2):311-7
299649
Science. 2001 Feb 9;291(5506):1043-7
11161216
Annu Rev Physiol. 2012;74:245-69
21942705
Int J Dev Biol. 2015 ;59(7-9):281-8
26679946
Cold Spring Harb Perspect Biol. 2011 Apr 01;3(4):null
21441584
Br J Pharmacol. 2012 Jun;166(4):1357-76
22242975
Dev Biol. 2006 Dec 15;300(2):534-44
16996050
Handb Exp Pharmacol. 2014;222:521-46
24756720
Genes Dev. 2012 May 1;26(9):920-32
22499591
Dev Biol. 2011 Feb 15;350(2):348-57
21145885
Q J Exp Physiol. 1984 Apr;69(2):365-80
6729022
J Cell Sci. 2013 Apr 1;126(Pt 7):1672-81
23424198
J Neurosci. 2004 Jun 2;24(22):5177-82
15175387
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):E225-33
22203997
Handb Exp Pharmacol. 2014;222:503-20
24756719
Nat Chem Biol. 2010 Sep;6(9):674-81
20693991
Dev Biol. 1996 Jul 10;177(1):178-89
8660886
Dev Biol. 1992 Jan;149(1):80-9
1728596
J Clin Invest. 2008 Nov;118(11):3671-81
18924610
Physiol Rev. 2006 Jan;86(1):25-88
16371595
Hum Reprod. 2005 Nov;20(11):3053-61
16055456
Dev Biol. 1992 Jul;152(1):94-102
1628759
Magnes Res. 2014 Jan-Mar;27(1):1-8
24721994
Nature. 2002 Jul 11;418(6894):186-90
12077606
J Invest Dermatol. 2012 Sep;132(9):2158-65
22622423
Nucleic Acids Res. 2015 Jan;43(Database issue):D771-6
25336621
Syst Biol Reprod Med. 2013 Apr;59(2):61-8
23311534
J Biol Chem. 2004 Aug 20;279(34):35741-8
15194687
J Gen Physiol. 2003 Jan;121(1):49-60
12508053
Pflugers Arch. 2014 Dec;466(12):2177-89
24633576