<i>HOXA10</i> and <i>HOXA11</i> in Human Endometrial Benign Disorders: Unraveling Molecular Pathways and Their Impact on Reproduction
<i>HOX</i> genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of <i>HOXA10/HOXA11</i> in reproductive health and their dysregulation in benign pa...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/4/563 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <i>HOX</i> genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of <i>HOXA10/HOXA11</i> in reproductive health and their dysregulation in benign pathologies associated with infertility, such as endometriosis, adenomyosis, and endometrial polyps. These genes are dynamically regulated by estrogen and progesterone, with peak expression during the secretory phase of the menstrual cycle when implantation takes place. The molecular mechanisms underlying their action include the modulation of extracellular matrix (ECM) remodeling via metalloproteinases, cytokines like leukemia inhibitory factor, and cell adhesion molecules such as β3-integrin, all of which are essential for the differentiation of epithelial and stromal cells, as well as for trophoblast invasion. Aberrant <i>HOX</i> gene expression, driven by DNA hypermethylation or altered histone acetylation, compromises endometrial receptivity and implantation. For instance, reduced <i>HOXA10</i> expression in endometriosis stems from hypermethylation and chronic inflammation, disrupting immune modulation and cytokine signaling. Similarly, adenomyosis alters <i>HOXA11</i>-regulated ECM remodeling and β3-integrin expression, impairing embryo attachment. Furthermore, regulatory pathways involving vitamin D and retinoic acid offer promising therapeutic avenues pathways, as they enhance <i>HOXA10/HOXA11</i> expression and endometrial receptivity. This review underscores the critical molecular roles of <i>HOXA10/HOXA11</i> genes as biomarkers and therapeutic targets to optimize fertility outcomes and address reproductive pathologies. |
|---|---|
| ISSN: | 2218-273X |