HOX Genes in Implantation

ABSTRACT

Implantation is a complex event requiring synchronization between a developing embryo and receptive endometrium. This process is governed by molecular mechanism mediated by homeobox (Hox) genes, which encode transcription factors. These factors guide embryologic development as well as regulate differential gene expression within the endometrium with each menstrual cycle. Spatiotemporal aberrations in HOX gene expression as seen with polycystic ovarian syndrome, endometriosis, hydrosalpinges, and endocrine disrupters compromise implantation. The role of HOX genes and their products continues to be explored as animal models that demonstrate implantation-specific infertile phenotypes continue to be investigated.

KEYWORDS

HOX - implantation - endometrium - pregnancy

REFERENCES

• 1 Aplin J D. The cell biological basis of human implantation.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 757-764
• 2 Red-Horse K, Zhou Y, Genbacev O et al.. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface.  J Clin Invest. 2004;  114 744-754
• 3 Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation.  Hum Reprod Update. 2006;  12 731-746
• 4 Taylor H S, Vandenheuvel G B, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system - late establishment and persistent adult expression of the Hoxa cluster genes.  Biol Reprod. 1997;  57 1338-1345
• 5 Lewis R W, Brooks N, Milburn G M et al.. The effects of the phytoestrogen genistein on the postnatal development of the rat.  Toxicol Sci. 2003;  71 74-83
• 6 Krumlauf R. Hox genes in vertebrate development.  Cell. 1994;  78 191-201
• 7 McGinnis W, Garber R L, Wirz J, Kuroiwa A, Gehring W J. A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans.  Cell. 1984;  37 403-408
• 8 McGinnis W, Krumlauf R. Homeobox genes and axial patterning.  Cell. 1992;  68 283-302
• 9 Kappen C, Schughart K, Ruddle F H. Early evolutionary origin of major homeodomain sequence classes.  Genomics. 1993;  18 54-70
• 10 Barnhart K T, Dunsmoor R, Coutifaris C. The effect of endometriosis on IVF outcome.  Fertil Steril. 2000;  77 1148-1155
• 11 Carlber M, Nejaty J, Froysa B. Elevated expression of tumor necrosis factor alpha in cultured granulosa cells from women with endometriosis.  Hum Reprod. 2000;  15 1250-1255
• 12 Giudice L C, Tazuke S I, Swiersz L. Status of current research on endometriosis.  J Reprod Med. 1998;  43 252-262
• 13 Hertig A T, Rock J, Adams E C. A description of 34 human ova within the first 17 days of development.  Am J Anat. 1956;  98 435-491
• 14 Schughart K, Kappen C, Ruddle F H. Mammalian homeobox-containing genes: genome organization, structure, expression and evolution.  Br J Cancer Suppl. 1988;  9 9-13
• 15 Kappen C. Disruption of the homeobox gene Hoxb-6 in mice results in increased numbers of early erythrocyte progenitors.  Am J Hematol. 2000;  65 111-118
• 16 Taylor H S. The role of HOX genes in human implantation.  Hum Reprod Update. 2000;  6 75-79
• 17 DeCherney A H, Cholst I, Naftolin F. Structure and function of the fallopian tubes following exposure to diethylstilbestrol (DES) during gestation.  Fertil Steril. 1981;  36 741-745
• 18 Block K, Kardana A, Igarashi P, Taylor H S. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system.  FASEB J. 2000;  14 1101-1108
• 19 Taylor H S, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium.  J Clin Invest. 1998;  101 1379-1384
• 20 Taylor H S, Igarashi P, Olive D, Arici A. Sex steroids mediate HOXA11 expression in human peri-implantation endometrium.  J Clin Endocrinol Metab. 1999;  84 1129-1135
• 21 Ma L, Benson G V, Lim H, Dev S K, Maas R L. Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in mullerian duct by the synthetic estrogen diethylstilbestrol (DES).  Dev Biol. 1998;  197 141-154
• 22 Taylor H S, Bagot C, Kardana A, Olive D L, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis.  Hum Reprod. 1999;  14 1328-1331
• 23 Benson G V, Lim H, Paria B C, Satokata I, Dey S K, Maas R L. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression.  Development. 1996;  122 2687-2696
• 24 Satokata I, Benson G, Maas R. Sexually dimorphic sterility phenotypes in Hoxa10 deficient mice.  Nature. 1995;  374 460-463
• 25 Hsieh-Li H M, Witte D P, Weinstein M et al.. Hoxa11 structure, extensive antisense transcription, and function in male and female fertility.  Development. 1995;  121 1373-1385
• 26 Gendron R L, Paradis H, Hsieh-Li H M, Lee D W, Potter S S. Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice.  Biol Reprod. 1997;  56 1097-1105
• 27 Cermik D, Selam B, Taylor H S. Regulation of HOXA10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 238-243
• 28 Bagot C N, Troy P J, Taylor H S. Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation.  Gene Ther. 2000;  7 1378-1384
• 29 Daftary G S, Taylor H S. Efficient liposome mediated gene transfection and expression in the intact human uterus.  Hum Gene Ther. 2001;  12 2121-2127
• 30 Daftary G S, Taylor H S. Reproductive tract gene transfer.  Fertil Steril. 2003;  80 475-484
• 31 Farrer-Brown G, Beilby J O, Tarbit M H. Venous changes in the endometrium of myomatous uterus.  Obstet Gynecol. 1971;  38 743-751
• 32 Stewart E A, Nowak R A. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era.  Hum Reprod Update. 1996;  2 295-306
• 33 Camus E, Poncelet C, Goffinet F et al.. Pregnancy rates after in vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies.  Hum Reprod. 1999;  14 1243-1249
• 34 Granot I, Dekel N, Segal I, Fieldust S, Shoham Z, Barash A. Is hydrosalpinx fluid cytotoxic?.  Hum Reprod. 1998;  13 1620-1624
• 35 Strandell A, Sjogren A, Bentin-Ley U, Thorburn J, Hamberger L, Brannstrom M. Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro.  Hum Reprod. 1998;  13 2921-2925
• 36 Murray C A, Clarke H J, Tulandi T, Tan S L. Inhibitory effect of human hydrosalpingeal fluid on mouse preimplantation embryonic development is significantly reduced by the addition of lactate.  Hum Reprod. 1997;  12 2504-2507
• 37 Daftary G S, Taylor H S. Hydrosalpinx fluid diminishes endometrial HOXA10 expression.  Fertil Steril. 2002;  78 577-580
• 38 Lessey B A, Castelbaum A JU, Sawin S W, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility.  Fertil Steril. 1995;  63 535-542
• 39 Meyer W R, Castelbaum A J, Somkuti S et al.. Hydrosalpinges adversely affect markers of endometrial receptivity.  Hum Reprod. 1997;  12 1393-1398
• 40 Mansour R T, Aboulghar M A, Serour G I, Riad R. Fluid accumulation in the uterine cavity before embryo transfer: a possible hindrance for implantation.  J In Vitro Fert Embryo Transf. 1991;  8 157-159
• 41 Fazleabas A T, Kim J J, Strakova Z. Implantation: embryonic signals and the modulation of the uterine environment-a review.  Placenta. 2004;  25(suppl A) S26-S31
• 42 Giudice L C, Swiersz L, Tazuke S I. Status of current research on endometriosis.  J Reprod Med. 1998;  43 252-262
• 43 Fowler D J, Nicolaides K H, Miell J P. Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract.  Hum Reprod Update. 2000;  6 495-504
• 44 Kim J J, Taylor H S, Akbas G E et al.. Regulation of insulin-like growth factor binding protein-1 promoter activity by FKHR and HOXA10 in primate endometrial cells.  Biol Reprod. 2003;  68 24-30
• 45 Tomita S, Li R K, Weisel R D et al.. Autologous transplantation of bone marrow cells improves damaged heart function.  Circulation. 1999;  100 II247-II256
• 46 Akbas G E, Song J, Taylor H SA. HOXA10 estrogen response element (ERE) is differentially regulated by 17 beta estradiol and diethylstilbestrol (DES).  J Mol Biol. 2004;  340 1013-1023
• 47 Martin R, Taylor M B, Krikun G, Lockwood C, Akbas G E, Taylor H S. Differential cell-specific modulation of HOXA10 by estrogen and specificity protein 1 response elements.  J Clin Endocrinol Metab. 2007;  92 1920-1926
• 48 Daftary G S, Taylor H S. Endocrine regulation of HOX genes.  Endocr Rev. 2006;  27 331-355
• 49 Troy P J, Daftary G S, Bagot C N, Taylor H S. Transcriptional repression of peri-implantation EMX2 expression in mammalian reproduction by HOXA10.  Mol Cell Biol. 2003;  23 1-13
• 50 Carson D D, Lagow E, Thathiah A et al.. Changes in gene expression during the early to mid-luteal (receptive) phase transition in human endometrium detected by high-density microarray screening.  Mol Hum Reprod. 2002;  8 871-879
• 51 Giudice L C. Application of functional genomics to primate endometrium: insights into biological processes.  Reprod Biol Endocrinol. 2006;  4(suppl 1) S4
• 52 Giudice L C, Telles T L, Lobo S, Kao L. The molecular basis for implantation failure in endometriosis: on the road to discovery.  Ann N Y Acad Sci. 2002;  955 252-264
• 53 Cross J C, Werb Z, Fischer S J. Implantation and the placenta: key pieces of the development puzzle.  Science. 1994;  266 1508-1518
• 54 Dey S K, Lim H, Das S K et al.. Molecular cues to implantation.  Endocr Rev. 2004;  25 341-373
• 55 Rossant J, Cross J C. Placental development: lessons from mouse mutants.  Nat Rev Genet. 2001;  2 538-548
• 56 Carter A M. Animal models of human placentation-a review.  Placenta. 2007;  28(suppl A) 41-47
• 57 Lee K Y, DeMayo F J. Animal models of implantation.  Reproduction. 2004;  128 679-695