Mishra Anuradha, Modi Deepak
Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive and Child Health, J.M. Street, Parel, Mumbai, 400 012, India.
Rev Endocr Metab Disord. 2025 Feb;26(1):81-96. doi: 10.1007/s11154-024-09923-8. Epub 2024 Nov 5.
HOXA10 belongs to the homeobox gene family and is essential for uterine biogenesis, endometrial receptivity, embryo implantation, and stromal cell decidualization. Available evidence suggests that the expression of HOXA10 is dysregulated in different endometrial disorders like endometrial hyperplasia, endometrial cancer, adenomyosis, endometriosis, recurrent implantation failure, and unexplained infertility. The downregulation of HOXA10 occurs by genetic changes in the HOXA10 gene, methylation of the HOXA10 locus, or selected miRNAs. Endocrine disruptors and organic pollutants also cause the reduced expression of HOXA10 in these conditions. In vivo experiments in mouse models and in vitro studies in human cell lines demonstrate that downregulation of HOXA10 leads to endometrial epithelial cell proliferation, failure of stromal cell decidualization, altered expression of genes involved in cell cycle regulation, immunomodulation, and various signaling pathways. These disruptions are speculated to cause infertility associated with the disorders of the endometrium.
HOXA10属于同源框基因家族，对子宫生物发生、子宫内膜容受性、胚胎着床及基质细胞蜕膜化至关重要。现有证据表明，HOXA10的表达在不同的子宫内膜疾病中失调，如子宫内膜增生、子宫内膜癌、子宫腺肌病、子宫内膜异位症、反复着床失败和不明原因不孕。HOXA10的下调通过HOXA10基因的遗传改变、HOXA10基因座的甲基化或特定的微小RNA发生。内分泌干扰物和有机污染物在这些情况下也会导致HOXA10表达降低。小鼠模型的体内实验和人类细胞系的体外研究表明，HOXA10的下调会导致子宫内膜上皮细胞增殖、基质细胞蜕膜化失败、细胞周期调控、免疫调节及各种信号通路相关基因的表达改变。据推测，这些干扰会导致与子宫内膜疾病相关的不孕。
