**1. Overview**

Hox genes are responsible for the expression of a large family of transcriptional factors that play a key role in embryonic development, organogenesis, and anteroposterior body orientation

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

[1, 2]. Even though the main function of these genes is well known during embryogenesis, their role in adults remains under investigation. Several studies have linked Hox genes with adult processes such as vascularization, hematopoiesis, tumor angiogenesis, and cell differentiation [3]. In this chapter, we will focus our attention on the origin and main role of Hox genes in adult tissues, especially on endothelial cell differentiation, neovasculogenesis, and angiogenesis.

serve as a promoter for many genes (motif TAAT) being a T in the direction 5′ determinant for this coupling acknowledgment [9]. Hox transcription factors are well known for playing a key role during cell and tissue differentiation in developing embryos; however, other studies have shown that these homeotic genes also play a role in adult process such as hematopoiesis and

Hox Genes in Adult Tissues and Their Role in Endothelial Cell Differentiation and Angiogenesis

http://dx.doi.org/10.5772/intechopen.76745

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Hox genes are crucial during endometrium redevelopment and corpus luteum formation because they regulate cell growth and differentiation during each reproductive cycle [10]. Expression of HoxA10 in human epithelial and stromal endometrial cells has been significantly higher in the intermediate and late phase of the menstrual cycle, suggesting that it could favor the implantation of the embryo [11–13]. Mechanistically, the protein encoded by this gene regulates the expression of several proteins related to endometrial development such as Emx2/EMX2, integrin β3, insulin-like growth factor-binding protein-1 (IGFBP-1), cyclin inhibitors, Wnt family genes, and the prostaglandin receptors EP-3 and EP-4 [14, 15]. Endometrium development is regulated by estrogen and progesterone; thus, any regulation of Hox genes by these hormones suggests that these genes play a role in the growth and development of the endometrium. For example, 17β-estradiol and progesterone significantly increased the expression of HoxA10 in endometrial cells [16] and primary culture of stromal endometrial cells, respectively, with a higher response induced by progesterone compared to 17β-estradiol [17] and even higher when both hormones were used in combination [17, 18]. *HOXA11* is another hox gene from the A cluster that has been closely associated with morphological alterations [19]. During the development of the female reproductive tract, *HOXA11* is normally expressed in the cervix and lower uterine segment. When the expression of this gene is impaired, it promotes aberrant epithelial cell differentiation leading to epithelial ovarian neoplasia [20, 21]. In addition, *HOXA11*−/− mice exhibit reduced development of the stroma in the glandular tissue and decidua during pregnancy [18, 22], suggesting a role in myometrium preparation to implantation. More recently, Yim et al. suggested that *HOXA11* promotes metastasis by regulating the expression of gene coding for metastasis-related proteins [23]. These findings indicate that *HOXA11* plays a role in the aggressive nature of ovarian cancer cells through *HOXA11* mediated expression of target genes such as matrix metalloproteinase (MMP) and VEGF.

Implantation is a series of sequential biological events triggered after fertilization in which the blastocyst migrates from the fallopian tube into the uterus. The fertilized egg is then attached to the uterine wall and subsequently implanted in the endometrium. Implantation occurs only in a very specific time period and place during the mid-secretory phase of the uterine cycle [24]. During this period, the uterus becomes more receptive by promoting a series of cellular and

embryo implantation by promoting neovasculogenesis and angiogenesis [10].

**3. Hox genes in adult-related processes**

**3.1. Endometrial tissue**

**3.2. Implantation**
