The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage-specific marker antigen F4/80 as well as inflammation-related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism-related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone-treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase-4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone-induced impairment of spermatogenesis.

中文翻译：

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支持细胞功能障碍参与糖皮质激素诱导的精子发生障碍

巨噬细胞特异性标志物抗原 F4/80 以及炎症相关基因的上调表明皮质酮诱导了睾丸炎症。皮质酮处理后睾丸和支持细胞中乳酸含量降低，乳酸代谢相关基因下调。体外吞噬作用测定表明，皮质酮处理的支持细胞中的吞噬活性被下调并伴随着线粒体膜电位的降低，而丙酮酸脱氢酶激酶-4 抑制剂的补充恢复了这一过程。总之，我们的研究结果表明，支持细胞中功能失调的吞噬能力和乳酸代谢参与了皮质酮诱导的精子发生障碍。皮质酮处理后睾丸和支持细胞中乳酸含量降低，乳酸代谢相关基因下调。体外吞噬作用测定表明，皮质酮处理的支持细胞中的吞噬活性被下调并伴随着线粒体膜电位的降低，而丙酮酸脱氢酶激酶-4 抑制剂的补充恢复了这一过程。总之，我们的研究结果表明，支持细胞中功能失调的吞噬能力和乳酸代谢参与了皮质酮诱导的精子发生障碍。皮质酮处理后睾丸和支持细胞中乳酸含量降低，乳酸代谢相关基因下调。体外吞噬作用测定表明，皮质酮处理的支持细胞中的吞噬活性被下调并伴随着线粒体膜电位的降低，而丙酮酸脱氢酶激酶-4 抑制剂的补充恢复了这一过程。总之，我们的研究结果表明，支持细胞中功能失调的吞噬能力和乳酸代谢参与了皮质酮诱导的精子发生障碍。体外吞噬作用测定表明，皮质酮处理的支持细胞中的吞噬活性被下调并伴随着线粒体膜电位的降低，而丙酮酸脱氢酶激酶-4 抑制剂的补充恢复了这一过程。总之，我们的研究结果表明，支持细胞中功能失调的吞噬能力和乳酸代谢参与了皮质酮诱导的精子发生障碍。体外吞噬作用测定表明，皮质酮处理的支持细胞中的吞噬活性被下调并伴随着线粒体膜电位的降低，而丙酮酸脱氢酶激酶-4 抑制剂的补充恢复了这一过程。总之，我们的研究结果表明，支持细胞中功能失调的吞噬能力和乳酸代谢参与了皮质酮诱导的精子发生障碍。