title: The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review.
abstract: OBJECTIVE
  endometriosis and its associated infertility have been the object of continuous research for over a century. To understand the molecular mechanisms underlying the disease, it has become necessary to determine the aspects of its etiology that are not explained by the retrograde menstruation theory. This could in turn elucidate how various clinical and surgical treatments might affect the evolution and remission of the disease.
  
  
  METHODS
  this review is focused on the most recent clinical and laboratory findings regarding the association of HOXA10 with endometriosis and infertility.
  
  
  RESULTS
  the homebox (Hox/HOX) proteins are highly conserved transcription factors that determine segmental body identities in multiple species, including humans. Hoxa10/HOXA10 is directly involved in the embryogenesis of the uterus and embryo implantation via regulation of downstream genes. Cyclical endometrial expression of Hoxa10/HOXA10, with a peak of expression occurring during the window of implantation, is observed in the adult in response to estrogen and progesterone. Women with endometriosis do not demonstrate the expected mid-luteal rise of HOXA10 expression, which might partially explain the infertility observed in many of these patients. Recent studies also demonstrated HOXA10 expression in endometriotic foci outside the Müllerian tract.
  
  
  CONCLUSIONS
  multiple lines of evidence suggest that the actions of the homeobox A10 (Hoxa10/HOXA10) gene could account for some aspects of endometriosis.
authors.affiliation: Huntington Medicina Reprodutiva, Av. República do Líbano, 529-Ibirapuera, 04501-000 São Paulo, SP, Brazil. alysson.zanatta@gmail.com
authors.forename: Alysson
authors.initials: A
authors.lastname: Zanatta
authors.forename: André M
authors.initials: AM
authors.lastname: Rocha
authors.forename: Filomena M
authors.initials: FM
authors.lastname: Carvalho
authors.forename: Ricardo M A
authors.initials: RM
authors.lastname: Pereira
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Eduardo L A
authors.initials: EL
authors.lastname: Motta
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Baracat
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Serafini
mesh_terms: D000328:Adult; D010064:Embryo Implantation; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000009:adverse effects* / Q000235:genetics; D006801:Humans; D007247:Infertility, Female / Q000209:etiology* / Q000235:genetics*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004967:Estrogens; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C069634:HOXA10 protein, human; D011374:Progesterone
references.citation: Development. 1997 May;124(9):1653-64
references.pmid: 9165114
references.citation: Hum Reprod. 2003 Jan;18(1):157-61
references.pmid: 12525459
references.citation: Cell. 1989 May 5;57(3):347-9
references.pmid: 2566382
references.citation: Gene Ther. 2000 Aug;7(16):1378-84
references.pmid: 10981664
references.citation: Gynecol Endocrinol. 2009 Mar;25(3):149-58
references.pmid: 19347704
references.citation: Fertil Steril. 2009 May;91(5):1686-91
references.pmid: 18672236
references.citation: Mol Hum Reprod. 2008 Jun;14(6):357-66
references.pmid: 18456676
references.citation: Hum Reprod. 2009 Dec;24(12):3180-7
references.pmid: 19736237
references.citation: J Clin Endocrinol Metab. 2006 Jun;91(6):2366-72
references.pmid: 16551735
references.citation: J Clin Endocrinol Metab. 2004 May;89(5):2390-6
references.pmid: 15126568
references.citation: EMBO J. 1988 Aug;7(8):2569-78
references.pmid: 2461299
references.citation: Fertil Steril. 2006 May;85(5):1386-90
references.pmid: 16647375
references.citation: Mol Hum Reprod. 2007 May;13(5):323-32
references.pmid: 17350963
references.citation: Hum Reprod. 1994 Apr;9(4):725-9
references.pmid: 8046030
references.citation: Mol Endocrinol. 2005 Sep;19(9):2222-33
references.pmid: 15905361
references.citation: Development. 1996 Sep;122(9):2687-96
references.pmid: 8787743
references.citation: J Minim Invasive Gynecol. 2009 Mar-Apr;16(2):174-80
references.pmid: 19249705
references.citation: Nature. 1978 Dec 7;276(5688):565-70
references.pmid: 103000
references.citation: Nature. 1995 Mar 30;374(6521):460-3
references.pmid: 7700356
references.citation: Hum Reprod. 1998 Jul;13(7):1825-30
references.pmid: 9740433
references.citation: J Clin Endocrinol Metab. 2003 Jan;88(1):238-43
references.pmid: 12519859
references.citation: J Am Assoc Gynecol Laparosc. 1995 Nov;3(1):55-9
references.pmid: 9050617
references.citation: Biol Reprod. 1997 May;56(5):1097-105
references.pmid: 9160706
references.citation: Blood. 2007 May 1;109(9):3687-96
references.pmid: 17234739
references.citation: Am J Obstet Gynecol. 2004 May;190(5):1404-6
references.pmid: 15167850
references.citation: Endocr Rev. 2006 Jun;27(4):331-55
references.pmid: 16632680
references.citation: J Clin Endocrinol Metab. 2000 Aug;85(8):2897-902
references.pmid: 10946900
references.citation: Histopathology. 1997 May;30(5):430-42
references.pmid: 9181364
references.citation: Hum Reprod. 2006 Mar;21(3):774-81
references.pmid: 16449312
references.citation: Development. 1992 Oct;116(2):357-68
references.pmid: 1363087
references.citation: Int J Gynecol Pathol. 1994 Oct;13(4):348-58
references.pmid: 7814197
references.citation: Fertil Steril. 2002 Oct;78(4):686-93
references.pmid: 12372441
references.citation: Arch Gynecol Obstet. 2000 Sep;264(2):88-9
references.pmid: 11045330
references.citation: Fertil Steril. 1996 Mar;65(3):603-7
references.pmid: 8774295
references.citation: Hum Reprod. 2006 Jul;21(7):1839-45
references.pmid: 16543256
references.citation: Fertil Steril. 2002 Sep;78(3):577-80
references.pmid: 12215336
references.citation: Cell. 1994 Jul 29;78(2):191-201
references.pmid: 7913880
references.citation: Gynecol Obstet Invest. 2003;55(2):63-7
references.pmid: 12771451
references.citation: Nature. 1984 Mar 29-Apr 4;308(5958):428-33
references.pmid: 6323992
references.citation: J Exp Clin Cancer Res. 2009 Apr 09;28:49
references.pmid: 19358700
references.citation: Cell. 1992 Jan 24;68(2):283-302
references.pmid: 1346368
references.citation: Fertil Steril. 2002 Jun;77(6):1148-55
references.pmid: 12057720
references.citation: J Clin Endocrinol Metab. 2006 Jan;91(1):228-38
references.pmid: 16249290
references.citation: J Clin Endocrinol Metab. 1999 Mar;84(3):1129-35
references.pmid: 10084606
references.citation: Hum Reprod. 1999 May;14(5):1328-31
references.pmid: 10325287
references.citation: Am J Obstet Gynecol. 2005 Aug;193(2):371-80
references.pmid: 16098858
references.citation: Obstet Gynecol Clin North Am. 1997 Jun;24(2):235-58
references.pmid: 9163765
references.citation: Fertil Steril. 2007 Dec;88(6):1505-33
references.pmid: 17462640
references.citation: Obstet Gynecol. 1984 Aug;64(2):151-4
references.pmid: 6234483
references.citation: J Clin Endocrinol Metab. 1994 Aug;79(2):643-9
references.pmid: 7519194
references.citation: Mol Endocrinol. 2005 Nov;19(11):2839-46
references.pmid: 15994197
references.citation: Mol Cell Biol. 2003 Jan;23(1):1-13
references.pmid: 12482956
references.citation: N Engl J Med. 2009 Jan 15;360(3):268-79
references.pmid: 19144942
references.citation: Dev Biol. 1998 May 15;197(2):141-54
references.pmid: 9630742
references.citation: J Clin Invest. 1998 Apr 1;101(7):1379-84
references.pmid: 9525980
references.citation: Endocrinology. 2003 Jul;144(7):2870-81
references.pmid: 12810542
references.citation: Biol Reprod. 2009 Jan;80(1):79-85
references.pmid: 18799756
references.citation: J Minim Invasive Gynecol. 2006 Jan-Feb;13(1):49-54
references.pmid: 16431323
references.citation: J Clin Endocrinol Metab. 2001 Jul;86(7):3387-92
references.pmid: 11443215
references.citation: Biol Reprod. 1997 Dec;57(6):1338-45
references.pmid: 9408238
references.citation: Annu Rev Physiol. 2005;67:285-308
references.pmid: 15709960
references.citation: Hum Reprod. 1992 Nov;7(10):1461-6
references.pmid: 1291578
references.citation: Fertil Steril. 2007 Feb;87(2):367-72
references.pmid: 17173899