title: Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition.
abstract: In mammals, uterine epithelium is remodeled cyclically throughout adult life for pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in maternal reproduction is unclear. Here, we addressed this issue by examining uterine secretions collected from patients undergoing fertility treatment and fertilization-competent Cd9(-/-) mice expressing CD9-GFP in their eggs (Cd9(-/-)TG). CD9 in uterine secretions was observed as extracellular matrix-like feature, and its amount of the secretions associated with repeated pregnancy failures. We also found that the litter size of Cd9(-/-)TG female mice was significantly reduced after their first birth. Severely delayed re-epithelialization of the endometrium was then occurred. Concomitantly, vascular endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions of Cd9(-/-)TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.
authors.affiliation: 1] Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan [2].
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kawano
authors.affiliation: Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyado
authors.affiliation: 1] Fertility Clinic Tokyo, 3-13-11 Higashi, Shibuya, Tokyo, Japan [2].
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshii
authors.affiliation: Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Kanai
authors.affiliation: Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Miyado
authors.affiliation: Saint Women's Clinic, 9-1 Higashitakasagocho, Urawa, Saitama, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Fertility Clinic Tokyo, 3-13-11 Higashi, Shibuya, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Odawara
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hamatani
authors.affiliation: Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
mesh_terms: D000328:Adult; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D060245:Tetraspanin 29 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D060245:Tetraspanin 29; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases
references.citation: Science. 1994 Dec 2;266(5190):1508-18
references.pmid: 7985020
references.citation: FASEB J. 2008 Oct;22(10):3571-80
references.pmid: 18606863
references.citation: Cell Tissue Res. 2007 Apr;328(1):197-206
references.pmid: 17186309
references.citation: Annu Rev Biophys Biomol Struct. 1992;21:417-39
references.pmid: 1525472
references.citation: Int Immunol. 2005 Jul;17(7):879-87
references.pmid: 15908444
references.citation: EMBO Mol Med. 2013 Sep;5(9):1415-30
references.pmid: 23853117
references.citation: Methods Enzymol. 1982;83:444-58
references.pmid: 7098947
references.citation: Nat Med. 2003 Jun;9(6):669-76
references.pmid: 12778165
references.citation: Hum Reprod Update. 2005 Nov-Dec;11(6):613-30
references.pmid: 16006437
references.citation: FEBS Lett. 2009 Mar 4;583(5):897-902
references.pmid: 19302789
references.citation: Blood. 1990 Jul 1;76(1):112-6
references.pmid: 2364164
references.citation: Nat Genet. 2000 Mar;24(3):279-82
references.pmid: 10700183
references.citation: J Exp Med. 2000 Jul 17;192(2):259-70
references.pmid: 10899912
references.citation: J Biol Chem. 2003 Mar 28;278(13):10963-72
references.pmid: 12519789
references.citation: Reproduction. 2003 Mar;125(3):301-11
references.pmid: 12611594
references.citation: J Biol Chem. 2002 Oct 25;277(43):40335-41
references.pmid: 12151391
references.citation: Reproduction. 2005 Nov;130(5):721-9
references.pmid: 16264101
references.citation: Curr Protoc Neurosci. 2009 Jul;Appendix 4:Appendix 4I
references.pmid: 19575469
references.citation: PLoS One. 2010 Oct 15;5(10):e13380
references.pmid: 20976164
references.citation: Nat Immunol. 2011 Jan;12(1):21-7
references.pmid: 21113163
references.citation: J Anat. 2009 Jul;215(1):3-13
references.pmid: 19453302
references.citation: Trends Immunol. 2004 Feb;25(2):75-84
references.pmid: 15102366
references.citation: Ann N Y Acad Sci. 2008;1135:10-8
references.pmid: 18574203
references.citation: Science. 2000 Jan 14;287(5451):321-4
references.pmid: 10634791
references.citation: Biochem Biophys Res Commun. 2001 Dec 14;289(4):782-90
references.pmid: 11735113
references.citation: Mol Hum Reprod. 2000 Mar;6(3):252-7
references.pmid: 10694273
references.citation: Reproduction. 2006 Apr;131(4):721-32
references.pmid: 16595723
references.citation: PLoS One. 2013;8(3):e58502
references.pmid: 23516492
references.citation: Int Rev Immunol. 1998;16(5-6):501-22
references.pmid: 9646174
references.citation: PLoS One. 2012;7(7):e42064
references.pmid: 22848702
references.citation: Immunity. 2002 Oct;17(4):413-23
references.pmid: 12387736
references.citation: Am J Reprod Immunol. 1997 Jul;38(1):1-5
references.pmid: 9266003
references.citation: Hum Reprod. 1992 Feb;7(2):156-61
references.pmid: 1349612
references.citation: J Cell Biol. 2007 Aug 13;178(4):701-11
references.pmid: 17682053
references.citation: Development. 1998 Jul;125(13):2415-24
references.pmid: 9609824
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188-92
references.pmid: 7901851
references.citation: J Assist Reprod Genet. 2009 Jun;26(6):327-34
references.pmid: 19597982
references.citation: Nat Cell Biol. 2007 Jun;9(6):654-9
references.pmid: 17486113
references.citation: Immunity. 2010 Aug 27;33(2):266-78
references.pmid: 20727790
references.citation: J Exp Med. 1991 Dec 1;174(6):1347-54
references.pmid: 1720807
references.citation: J Natl Cancer Inst. 1980 Jul;65(1):81-93
references.pmid: 6248674
references.citation: Biol Reprod. 1997 May;56(5):1181-8
references.pmid: 9160717
references.citation: Nat Rev Drug Discov. 2008 Sep;7(9):747-58
references.pmid: 18758472
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12921-6
references.pmid: 18728192
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10159-62
references.pmid: 8234270
references.citation: J Cell Biol. 1999 Nov 1;147(3):599-610
references.pmid: 10545503
references.citation: Proc Soc Exp Biol Med. 1950 May;74(1):106-8
references.pmid: 15430405
references.citation: Biol Reprod. 1998 Jul;59(1):22-9
references.pmid: 9674989
references.citation: J Clin Invest. 1993 Apr;91(4):1834-7
references.pmid: 8473523
references.citation: Fertil Steril. 2009 Apr;91(4):1145-51
references.pmid: 18331736
references.citation: J Cell Sci. 2000 Oct;113 Pt 19:3365-74
references.pmid: 10984428
references.citation: Science. 2000 Jan 14;287(5451):319-21
references.pmid: 10634790