HOXC and HOXD gene expression in human endometrium: Lack of redundancy with HOXA paralogs
HOXC and HOXD gene expression in human endometrium: Lack of redundancy with HOXA paralogs
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DOI：
10.1095/biolreprod.102.014969
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Akbas, GE;Taylor, HS
HOXA 基因是胚胎分化的重要调节因子，对于成人周期性子宫内膜发育和子宫内膜容受性也至关重要。缺乏 Hoxa10 或 Hoxa11 的小鼠由于着床缺陷而表现出生育能力下降。我们假设 HOXC10、HOXC11、HOXD10 和 HOXD11（HOXA10 和 HOXA11 的旁系同源物）也可能参与子宫内膜发育。在这里，我们通过半定量逆转录聚合酶链反应表明，HOXC10、HOXC11、HOXD10 和 HOXD11 在子宫内膜的整个月经周期中都有明显的表达。在分泌期，HOXC10、HOXC11和HOXD11的表达量下降至增殖期表达量的4%，HOXD10下降至25%（分别为P < 0.001、P < 0.001、P < 0.02、P < 0.01）。原位杂交证明了这些 HOX 基因的表达主要在基质中，并证实了分泌期表达的减少。原代子宫内膜基质细胞或 Ishikawa 细胞中 HOXC10、HOXC11、HOXD10 和 HOXD11 的表达不受性类固醇的调节。 HOXC和HOXD基因的表达和调控与HOXA10和HOXA11不同。 HOXA10 和 HOXA11 是子宫内膜分化的调节因子，而 HOXC 和 HOXD 基因可能调节子宫内膜增殖。旁系同源 HOX 基因通常在发育过程中具有冗余功能；旁系同源 Hox 基因的一种新的进化分歧导致 HOXC 和 HOXD 基因具有与 HOXA 基因不同的表达模式、调节，并且可能还具有不同的功能。 HOX 基因网络可能参与调节子宫内膜发育的多个方面，包括增殖和分化。
HOXA genes, essential regulators of differentiation in the embryo, are also essential for adult cyclic endometrial development and for endometrial receptivity. Mice deficient in Hoxa10 or Hoxa11 exhibit reduced fertility because of defects in implantation. We hypothesized that HOXC10, HOXC11, HOXD10, and HOXD11, paralogs of HOXA10 and HOXA11, might also be involved in endometrial development. Here, we showed that the expression of HOXC10, HOXC11, HOXD10, and HOXD11 was evident throughout the menstrual cycle in the endometrium by semiquantitative reverse transcription-polymerase chain reaction. In the secretory phase, expression of HOXC10, HOXC11, and HOXD11 decreased to 4% and HOXD10 decreased to 25% of the proliferative phase expression (P < 0.001, P < 0.001, P < 0.02, P < 0.01, respectively). In situ hybridization demonstrated expression of each of these HOX genes primarily in the stroma and confirmed the decreased expression in the secretory phase. HOXC10, HOXC11, HOXD10, and HOXD11 expression was not regulated by sex steroids in primary endometrial stromal cells or Ishikawa cells. The expression and regulation of HOXC and HOXD genes varies from that of HOXA10 and HOXA11. Whereas HOXA10 and HOXA11 are regulators of endometrial differentiation, HOXC and HOXD genes likely regulate endometrial proliferation. Paralogous HOX genes typically have a redundant function in development; a novel evolutionary divergence of paralogous Hox genes has resulted in HOXC and HOXD genes having distinct expression patterns, regulation, and likely also distinct functions from HOXA genes. A network of HOX genes may be involved in regulating multiple aspects of endometrial development, including both proliferation and differentiation.