title: The human oviduct transcriptome reveals an anti-inflammatory, anti-angiogenic, secretory and matrix-stable environment during embryo transit.
abstract: The human oviduct serves as a conduit for spermatozoa in the peri-ovulatory phase and nurtures and facilitates transport of the developing embryo for nidation during the luteal phase. Interactions between the embryo and oviductal epithelial surface proteins and secreted products during embryo transit are largely undefined. This study investigated gene expression in the human oviduct in the early luteal versus follicular phases to identify candidate genes and biomolecular processes that may participate in maturation and transport of the embryo as it traverses this tissue. Oviductal RNA was hybridized to oligonucleotide arrays and resulting data were analysed by bioinformatic approaches. There were 650 genes significantly down-regulated and 683 genes significantly up-regulated (P<0.05) in the luteal versus follicular phase. Quantitative real-time PCR, immunoblot analysis and immunohistochemistry confirmed selected gene expression and cellular protein localization. Down-regulated genes involved macrophage recruitment, immunomodulation and matrix-degeneration, and up-regulated genes involved anti-inflammatory, ion transport, anti-angiogenic and early pregnancy recognition. The oviduct displayed some similarities and differences in progesterone-regulated genes compared with the human endometrium. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through human oviduct and some conservation of progesterone signalling in tissues of common embryological origin. The oviduct serves as a conduit for spermatozoa in the peri-ovulatory phase and it nurtures and facilitates transport of the developing embryo during the luteal phase of the menstrual cycle, although precise interactions between the embryo and oviductal epithelium and secreted products are largely undefined. Herein, we investigated gene expression in human oviduct to identify candidate genes and processes that may participate in maturation and transport of the embryo as it develops implantation competence. Total RNA from human ampullary oviducts in the early luteal versus follicular phases was isolated and hybridized to oligonucleotide arrays. The data, analysed by bioinformatic approaches, revealed that 650 genes were significantly down- and 683 genes were significantly up-regulated in the luteal phase. Quantitative real-time PCR, immunoblot analysis and immunohistochemistry confirmed selected gene expression and cellular protein localization. The data demonstrated down-regulation of genes involved in macrophage recruitment, immunomodulation and matrix degeneration and up-regulation of ion transport and secretions, as well as anti-angiogenic and early pregnancy recognition. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through the human oviduct and provide insight into mechanisms influencing acquisition of implantation competence of the human embryo during its passage through the oviduct en route to the uterine endometrium.
authors: Department of Gynecology and Obstetrics, Stanford University Medical School, CA, USA; University of Dusseldorf, Medical Faculty, Department of Gynecology, Obstetrics and REI (UniKiD), Dusseldorf, Germany.
authors: A P
authors: AP
authors: Hess
authors: S
authors: S
authors: Talbi
authors: A E
authors: AE
authors: Hamilton
authors: D M
authors: DM
authors: Baston-Buest
authors: M
authors: M
authors: Nyegaard
authors: J C
authors: JC
authors: Irwin
authors: F
authors: F
authors: Barragan
authors: J S
authors: JS
authors: Kruessel
authors: A
authors: A
authors: Germeyer
authors: L C
authors: LC
authors: Giudice
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D005187:Fallopian Tubes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D056747:Immunomodulation / Q000235:genetics; D008183:Luteal Phase; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012313:RNA / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D012313:RNA
keywords: angiogenesis; human Fallopian tube; immunomodulation; implantation; progesterone
references: Hum Reprod. 1996 Aug;11(8):1678-86
references: 8921116
references: Biostatistics. 2003 Apr;4(2):249-64
references: 12925520
references: Nucleic Acids Res. 2001 May 1;29(9):e45
references: 11328886
references: Br J Obstet Gynaecol. 1977 Mar;84(3):219-21
references: 843499
references: Mol Hum Reprod. 2002 Sep;8(9):871-9
references: 12200466
references: Nature. 2000 Mar 23;404(6776):407-11
references: 10746730
references: Fertil Steril. 1992 Sep;58(3):569-74
references: 1521654
references: Biochem J. 2009 Mar 15;418(3):475-89
references: 19228121
references: FASEB J. 2005 Jul;19(9):1056-60
references: 15985528
references: Nucleic Acids Res. 2002 May 1;30(9):e36
references: 11972351
references: J Exp Med. 1996 Sep 1;184(3):799-802
references: 9064339
references: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7220-5
references: 10377395
references: Mol Hum Reprod. 2003 Jan;9(1):19-33
references: 12529417
references: Reprod Biomed Online. 2003 Jun;6(4):470-81
references: 12831597
references: Genomics. 1991 Jan;9(1):200-3
references: 2004761
references: J Exp Zool A Ecol Genet Physiol. 2007 Jan 1;307(1):28-34
references: 17094107
references: Mol Cell Biol. 1994 Dec;14(12):8408-19
references: 7526157
references: J Leukoc Biol. 2001 Jun;69(6):912-20
references: 11404376
references: Stat Methods Med Res. 1992;1(1):69-95
references: 1341653
references: J Immunol. 1990 Mar 15;144(6):2377-83
references: 2313097
references: Hum Reprod Update. 1997 Jul-Aug;3(4):367-82
references: 9459282
references: Endocrinology. 2007 Aug;148(8):3814-26
references: 17510236
references: Hum Reprod. 1994 Dec;9(12):2224-33
references: 7714136
references: Biol Proced Online. 2006;8:175-93
references: 17242735
references: Endocr Rev. 2007 Dec;28(7):707-25
references: 17916741
references: J Clin Endocrinol Metab. 2009 Dec;94(12):5146-54
references: 19864448
references: J Assist Reprod Genet. 2005 Dec;22(11-12):429-35
references: 16331541
references: Biochem J. 2005 Feb 15;386(Pt 1):15-27
references: 15554875
references: J Reprod Immunol. 2011 Apr;89(1):84-91
references: 21414667
references: Endocrinology. 2002 Jun;143(6):2119-38
references: 12021176
references: Hum Reprod. 2007 Feb;22(2):356-61
references: 17043099
references: Hum Reprod. 1995 Jun;10(6):1571-8
references: 7593541
references: Endocrinology. 2006 Mar;147(3):1097-121
references: 16306079
references: Hum Reprod. 1992 Sep;7(8):1144-9
references: 1400940
references: Biol Reprod. 2007 Jan;76(1):102-17
references: 17021345
references: Nat Genet. 2000 May;25(1):25-9
references: 10802651
references: Dev Biol. 2006 Oct 1;298(1):107-17
references: 16930583
references: Semin Cell Dev Biol. 2004 Apr;15(2):237-46
references: 15209384
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8
references: 15980575
references: Hum Reprod. 2005 Jun;20(6):1439-46
references: 15734755
references: J Assist Reprod Genet. 1996 Nov;13(10):772-5
references: 8986587
references: Physiol Genomics. 2001 Dec 21;7(2):135-48
references: 11773600
references: J Clin Invest. 1987 Feb;79(2):319-26
references: 3543052
references: BMC Bioinformatics. 2004 Feb 18;5:16
references: 14975175
references: Nature. 1979 Jun 7;279(5713):523-5
references: 571963
references: Nature. 1980 Jul 17;286(5770):266-7
references: 6157101
references: Free Radic Biol Med. 2010 Dec 1;49(11):1638-45
references: 20727966
references: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7732-6
references: 2217207
references: Reprod Biol Endocrinol. 2004 Jun 16;2:34
references: 15200677
references: Ann N Y Acad Sci. 2003 May;995:183-90
references: 12814950
references: Biol Reprod. 2009 Jan;80(1):105-14
references: 18815356
references: Hum Reprod. 2006 Sep;21(9):2281-9
references: 16763010
references: Lancet. 1999 Nov 6;354(9190):1579-85
references: 10560671
references: Mol Hum Reprod. 2002 Apr;8(4):375-84
references: 11912286
references: Ann Clin Lab Sci. 1973 Mar-Apr;3(2):108-17
references: 4707984
references: Endocrinology. 2000 Sep;141(9):3510-3
references: 10965925
references: Hum Reprod. 2008 Sep;23(9):1993-2000
references: 18556682
references: Reprod Biol Endocrinol. 2010 Nov 02;8:133
references: 21044331
references: Reprod Biol Endocrinol. 2004 Jul 07;2:54
references: 15239838
references: Hum Reprod Update. 2010 Jul-Aug;16(4):432-44
references: 20071358
references: Trends Cell Biol. 2000 Aug;10(8):335-42
references: 10884686
references: Biol Pharm Bull. 2006 Dec;29(12):2343-9
references: 17142960
references: Eur J Obstet Gynecol Reprod Biol. 1997 May;73(1):99-104
references: 9175697
references: Science. 2003 Jan 17;299(5605):405-8
references: 12532021
references: Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S20-4
references: 10673221
references: Fertil Steril. 2009 Mar;91(3):767-76
references: 18321489
references: Trends Immunol. 2004 Apr;25(4):201-9
references: 15039047
references: Lancet. 1992 Jul 4;340(8810):17-8
references: 1351601
references: Hum Reprod. 1997 Jun;12(6):1253-8
references: 9222012
references: Endocrinology. 2003 Jul;144(7):2870-81
references: 12810542
references: J Immunol. 1990 Apr 15;144(8):3034-8
references: 2182712
references: Fertil Steril. 1998 Jan;69(1):84-8
references: 9457939