Endometrial Receptivity

The limiting factor in achieving pregnancy for most couples is implantation- attachment of the embryo to the uterus. In in vitro fertilization (IVF), multiple embryos are transferred to the uterus with the hope that one will implant; unfortunately the transfer of more than one embryo sometimes results in multiple gestations with increased risk. The implantation step is still poorly understood. We have identified a role of the human HOXA10 gene in this process. This gene is one of the few know to be necessary for implantation to occur. We have characterized the normal role and regulation of this gene in the process of implantation and identified several diseases where it is abnormally expressed.

Expression of HOXA10 dramatically increased during the midsecretory phase of the menstrual cycle, corresponding to the time of implantation and increase in circulating progesterone. Expression of HOXA10 in cultured endometrial cells was stimulated by estrogen or progesterone. We identified sex steroids as novel regulators of HOX gene expression. HOXA10 has an important function in regulating endometrial development during the menstrual cycle and in establishing conditions necessary for implantation in the human and mouse. HOXA10 is necessary for implantation to occur. Targeted disruption results in abnormal endometrial receptivity and failed implantation. Transfer of HOXA10 antisense to the wild type mouse uterus prior to implantation blocks pregnancy, while constitutive expression of HOXA10 improves implantation and increases litter size.

HOXA10 expression is lower in the uteri of women with hydorsalpinx, PCOS, and endometriosis; all of these conditions are associated with diminished endometrial receptivity. We have identified several regulators of HOXA10 expression, specifically estradiol, progesterone, testosterone, and Vitamin D. HOXA10 functions as a transcription factor and we have also characterized several downstream targets of HOXA10 transcriptional regulation. We have shown that _3integrin, EMX2, and IGFBP-1 are direct downstream targets of HOXA10. Current research focuses on the identifying the majority of HOXA10 target genes in the endometrium; a microarray has led to the identification of multiple putative target genes.

We hope to further understand the molecular mechanisms underlying the implantation processes and thereby improve the chance of successful pregnancy.

  • Taylor HS, Arici A, Olive DL and Igarashi P. HOXA10 Is Expressed in Response to Sex Steroids at the Time of Implantation in the Human Endometrium. J Clin Invest 1998,101(7):1379-1384.
  • Troy PJ, Daftary G and Taylor HS. Transcriptional repression of peri-implantation of EMX2 expression in mammalian reproduction by HOXA10. Mol Cell Biol 2003, 23(1):1-13.
  • Taylor HS, Bagot C, Kardana A and Arici A. HOX Gene Expression Is Altered in the Endometrium of Women with Endometriosis. Hum Reprod 1999, 14(5):1328-1331.
  • Bagot C, Troy P and Taylor HS. Alteration of Maternal HOXA10 Expression by In Vivo Gene Transfection Affects Implantation. Gene Ther 2000, 7(16):1378-1384.
  • Daftary G and Taylor HS. Efficient Liposome Mediated Gene Transfection and Expression in the Intact Human Uterus. Hum Gene Ther 2001, 12(17):2121-2127.
  • Daftary GS and Taylor HS. Hydrosalpinx fluid diminishes endometrial HOXA10 expression. Fertil Steril 2002, 78(3): 577-80.
  • Cermik D, Selam B and Taylor HS. Regulation of HOXA10 expression by testosterone in vitro and in the endometrium of patients with PCOS. J Clin Endocrinol Metab 2003, 88(1):238-243.
  • Daftary GS and Taylor HS. Reproductive tract gene transfer. Fertil Steril 2003:80(3):475-484.
  • Tang M and Taylor HS, Tabibzadeh S. In vivo gene transfer of Lefty leads to implantation failure in mice. Hum Reprod 2005 20(7):1772-1778.
  • Troy PJ, Daftary G and Taylor HS. Transcriptional repression of peri-implantation of EMX2 expression in mammalian reproduction by HOXA10. Mol Cell Biol 2003, 23(1):1-13.
  • Sarno JL, Kliman H and Taylor HS. HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes. J Clin Endocrinol Metab 2005, 90(1):522-528.
  • Kwon HE and Taylor HS. The role of HOX genes in Human implantation. Ann NY Acad Sci. 2004, 1034:1-18.