Hypertension induces gonadal macrophage imbalance, inflammation, lymphangiogenesis, and dysfunction.
Hypertension induces gonadal macrophage imbalance, inflammation, lymphangiogenesis, and dysfunction.
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高血压引起性腺巨噬细胞失衡、炎症、淋巴管生成和功能障碍。
DOI：
10.1042/cs20220117
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发表时间：
2022-06-17
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高血压（HTN）与男性和女性的性腺功能障碍和生殖健康受损有关。在HTN动物中观察到全身和肾脏促炎（M1）/抗炎（M2）巨噬细胞比例失衡、炎症增加和炎症相关淋巴管生成。然而，HTN对性腺巨噬细胞、炎症和炎症的影响仍然不清楚。我们假设盐敏感性HTN（SSHTN）和HTN改变性腺巨噬细胞极化，这与炎症，炎症相关的淋巴管生成和生殖功能障碍。流式细胞术分析显示，SSHTN和硝基-L-精氨酸甲酯盐酸盐（L-NAME）诱导的HTN（LHTN）小鼠睾丸中M1巨噬细胞显著增加，同时SSHTN小鼠中M2巨噬细胞减少，但LHTN小鼠中M2巨噬细胞增加。SSHTN小鼠的卵巢显示M1巨噬细胞增加和M2巨噬细胞减少，而LHTN小鼠的卵巢显示M2巨噬细胞显著增加和M1巨噬细胞减少。促炎性细胞因子的基因表达模式揭示了所有高血压小鼠的性腺炎症。淋巴管内皮透明质酸受体1（LYVE-1）的免疫荧光染色证实了雄性和雌性高血压小鼠性腺中淋巴管密度的增加。HTN对睾丸和卵巢中类固醇生成酶、激素受体和分泌蛋白的表达模式产生不利影响。与这些结果一致，雄性高血压小鼠也表现出精子浓度降低，形态异常、顶体受损和线粒体活性丧失的精子百分比增加。这些数据表明，HTN改变性腺巨噬细胞极化，这是与性腺炎症，炎症相关的淋巴管生成，和功能障碍。
Hypertension (HTN) is associated with gonadal dysfunction and impaired reproductive health in both men and women. An imbalance in the systemic and renal proinflammatory (M1)/anti-inflammatory (M2) macrophage ratio, increased inflammation, and inflammation-associated lymphangiogenesis have been observed in animals with HTN. However, the impact of HTN on gonadal macrophages, inflammation, and lymphatics remains obscure. We hypothesized that salt-sensitive HTN (SSHTN) and HTN alters gonadal macrophage polarization, which is associated with inflammation, inflammation-associated lymphangiogenesis, and reproductive dysfunction. Flow cytometry analyses revealed a significant increase in M1 macrophages in the testes of SSHTN and nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced HTN (LHTN) mice, with a concurrent decrease in M2 macrophages in SSHTN mice yet an increase in M2 macrophages in LHTN mice. Ovaries from SSHTN mice exhibited an increase in M1 and a decrease in M2 macrophages, while ovaries from LHTN mice had a significant increase in M2 and a decrease in M1 macrophages. Gene expression patterns of proinflammatory cytokines revealed gonadal inflammation in all hypertensive mice. Increased lymphatic vessel density in the gonads of both male and female hypertensive mice was confirmed by immunofluorescence staining for lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). HTN adversely affected the expression pattern of steroidogenic enzymes, hormone receptors, and secretory proteins in both the testes and ovaries. In line with these results, male hypertensive mice also presented with decreased sperm concentration, and increased percentage of sperm with abnormal morphology, damaged acrosome, and nonfunctional mitochondrial activity. These data demonstrate that HTN alters gonadal macrophage polarization, which is associated with gonadal inflammation, inflammation-associated lymphangiogenesis, and dysfunction.