HOXA10 and HOXA11 in Human Endometrial Benign Disorders: Unraveling Molecular Pathways and Their Impact on Reproduction

Lorin-Manuel Pîrlog, Andrada-Adelaida Pătrășcanu, Mara-Diana Ona, Andreea Cătană, Ioana Cristina Rotar
Biomolecules · 2025 · vol. 15(4) , pp. 563 · doi:10.3390/biom15040563 · PMID:40305321 · W4409329327
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This review details how HOXA10 and HOXA11 gene dysregulation, driven by hormonal and epigenetic factors, impacts endometrial receptivity and implantation in conditions like endometriosis and adenomyosis.

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Abstract

HOX genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of HOXA10/HOXA11 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 HOX gene expression, driven by DNA hypermethylation or altered histone acetylation, compromises endometrial receptivity and implantation. For instance, reduced HOXA10 expression in endometriosis stems from hypermethylation and chronic inflammation, disrupting immune modulation and cytokine signaling. Similarly, adenomyosis alters HOXA11-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 HOXA10/HOXA11 expression and endometrial receptivity. This review underscores the critical molecular roles of HOXA10/HOXA11 genes as biomarkers and therapeutic targets to optimize fertility outcomes and address reproductive pathologies.

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Condition tags

mesh:D004715endometriosisadenomyosisinfertility

MeSH descriptors

Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (100)

Cited by (3)

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