Reproductive Medical Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Jul 22;13:928024. doi: 10.3389/fendo.2022.928024. eCollection 2022.
Adenomyosis is a common benign uterine lesion that is associated with female infertility, reduced clinical pregnancy rate and high miscarriage risk. While it has been known that the impaired endometrial receptivity is implicated in infertility in patients with adenomyosis, the underlying mechanism remains unclear. In the present study, we showed that intracellular protein level of IL-33 was downregulated in the endometrium of patients with adenomyosis, and IL-33 expression status was shown to be positively correlated with that of HOXA10, an endometrial receptivity marker. The subsequent analysis indicated IL-33 overexpression led to the increase of HOXA10 expression and enhancement of embryo implantation , which was accompanied with induction of STAT3 phosphorylation. Meanwhile, cryptotanshinone, a potent STAT3 inhibitor, was found to significantly suppress the increase of HOXA10 expression and embryo implantation caused by IL-33 overexpression , revealing the critical role of STAT3 activity. Consistently, the positive relationship between IL33 and HOXA10 expression in the endometrium was verified in the analysis of adenomyosis mouse model.
腺肌病是一种常见的良性子宫病变，与女性不孕、临床妊娠率降低和流产风险高有关。虽然已经知道，子宫内膜容受性受损与腺肌病患者的不孕有关，但潜在的机制仍不清楚。在本研究中，我们表明，腺肌病患者的子宫内膜中 IL-33 的细胞内蛋白水平下调，并且 IL-33 的表达状态与子宫内膜容受性标志物 HOXA10 的表达状态呈正相关。随后的分析表明，IL-33 的过表达导致 HOXA10 表达的增加和胚胎着床的增强，伴随着 STAT3 磷酸化的诱导。同时，隐丹参酮，一种有效的 STAT3 抑制剂，被发现可显著抑制由 IL-33 过表达引起的 HOXA10 表达增加和胚胎着床，揭示了 STAT3 活性的关键作用。一致地，在腺肌病小鼠模型的分析中验证了子宫内膜中 IL33 和 HOXA10 表达之间的正相关关系。
